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Medical Forum / Diseases and Disorders / Prostate Cancer / March 2008What to ask an oncologist (need help brainstorming)?
Hi, guys. First of all, a little update. My original, high-power Houston urologist responded to my question about my three recent detectable PSAs (after IMRT in 2005) w/ the recommendation to "sit tight" (his words) for 6 months and then retest. Now to where I'd like an input from all of you who are familiar w/ the post-radiation recurrence,and/or pro- and con- ADT issues, and other relevant oncology literature. I have a consult with an oncologist scheduled for 10 days from now. Of the large local oncology practice, he was recommended as the one w/ the most experience in prostate cancer. I'll have an hour to spend w/ him, and would like it to be spent productively, not just like, "Big Daddy. please tell me what to do." So, I'm hoping for your help w/ specific questions that I should ask him to make as informed decision as possible. Please don't hold back. I can really use your input and maybe my visit w/ him can be of help to some of you, too. SY > Please don't hold back. OK. Here's the e-mail I sent my uro onc before our first serious ADT discussion > three years ago. Maybe it will trigger some thoughts or questions. If the acronyms throw you, ask; it was written for him and my oncology team, not for patients. EARLY, ADJUVANT ADT RATIONALE for [I.P. Freely] Sorry this is so long, but I hope skimming this in advance will save you more precious clinic time on Friday. This explains my tentative position against early ADT; maybe you can change or reinforce it. Post-RP w/ Gleason 8 T3c, I anticipate a QOL graph consisting of several years of high, asymptomatic QOL, followed by biochemical failure, then clinical failure, as my QOL curve falls from great to OK to bad to intolerable to blessed relief. Early adjuvant ADT MAY prolong life by delaying recurrence and/or refraction, but WILL produce SEs which lower the QOL graph right out of the gate, MAY prolong heartbeat by a few months if at all, and may even exacerbate refraction. So I’ve spent the last six weeks studying a dozen cancer books and dozens of web sites, including Walsh, PCRI (Strum, Scholz, et.al,), Lange, Marks, Blasko, Oersterling, leading universities and hospitals, NCI, ACS, NEJM, JAMA, Lancet, the VA, Harrison’s Internal Medicine, etc. (I’ve researched medical issues on the web for many years and always wear hip boots.) MY STATUS With my PC numbers, www.prostatecalculator.org from VA => 15% chance of avoiding PSA failure for a decade. ADJUVANT TREATMENTS CONSIDERED WW, ADT1,2,3 (early or at biochemical or clinical failure), IAD, antiandrogen monotherapy, immunotherapy, angiogenesis, MAB, etc. MY SHORT LIST OF TREATMENT OPTIONS * WW until biochemical, maybe clinical, failure necessitates ADT, maybe plus * Early antiandrogen monotherapy or * Early immunotherapy or * New technologies such as Provenge or Aptosin. EARLY ADJUVANT ADT BENEFITS . . . OR LACK THEREOF * 5-yr-relapse-free ADT improvements run from negligible to 10-15% . . . not much benefit for the SEs. * Adjuvant ADT helped N=1 patients, but trials do not demonstrate clear advantages to ADT after RP w/N=0, even with PSA elevation. * Major meta-study found no evidence that early adjuvant ADT provides any advantage, even w/rising PSA; Walsh, the Mayo Clinic, Sloan-Kettering, the ACS, and universities agree (citing failure to prolong life, SEs, QOL, and accelerated refraction). * Pts w/asymptomatic mets MAY experience fewer serious complications with early, rather than late, ADT. * Finasteride monotherapy slightly improved prognosis, but => more, higher-grade refractory tumors. * ADT 2 or 3 (CAB) not promising, not curative, may promote refraction, no 5-yr benefit, more SEs. * IAD MAY delay refractory mutation, MAY extend heartbeat by 6-12 months, and MAY reduce side effects towards the end of each HT-off cycle . . . * Young [they call me that based on vitality] G8 T3c RP pts have unacceptably high relapse and refraction rates even with adjuvant ADT, * But it’s ineffective after biochemical failure w/Gleason >7. * T3c, G > 6, and/or aneuploidy => high p(AIPC) => low p(big ADT benefit). * All those results => little risk and much reward potential in delaying ADT at least until PSA DT is known. * (OTOH, accumulating evidence supports ADT w/locally advanced disease.) * Antiandrogen monotherapy w/Casodex reduces SEs to primarily gynecomastia, may be as effective as LHRH agonists or castration for locally advanced PC, and is approved in 60 countries for that purpose. ADTSIDE EFFECTS, DOWNSIDES, CONCERNS * ADT SEs, in approximate decreasing order of my concern about them: fatigue/weakness/lethargy/anemia (the earliest and most obvious andropause SE), depression, osteoporosis (seriously underreported) and attendant fractures, cognitive dysfunction, hot flashes/night sweats (and the SEs of meds that reduce them), extreme irritability, emotional turmoil, poor sleep, nausea, diarrhea, lipid elevation, liver damage, psychological stress, pronounced personality alteration, upper body muscle atrophy, weight gain, breast pain, insulin resistance, and libido/ED effects. (Surprised at that last one being last? Think about it; who’d want sex with all that other crap going on?) * ADT < 12 mo => patients suffer typical ACUTE Androgen Deprivation Syndrome (ADS; see Strum) – invariably compromising healthy, active lifestyles -- but maybe not significant CHRONIC symptoms. Chronic symptoms -- some nearly inevitable in patients treated > 12 mo -- are much more prevalent with ADT than is currently recognized or reported. * Probabilities of various SEs combine mathematically to virtually guarantee (p > .97) one or two SEs I’m not willing to accept just for a slight, debatable, statistical lifeline benefit. * Anti-SE meds (e.g., antidepressants, anabolic steroids, NSAIDS) have their own, major, SEs. * I have two conflicts with biphosphonates: NSAIDS give me ulcers and I’m on a PPI for GERD. * ADT after RP can extend life . . . if given for 28 months, but * Two years on ADT may permanently suppress T and thus maintain SEs, and * Trial ADT takes 6-12 months to reveal all its SEs – about the maximum extent of its lifeline extension. * ADT => T deprivation => SEs. T > 20 => little benefit. This may mean no pain (SEs), no gain. * ADT drives PSA down, hiding the REAL killer, AIPC, while it proliferates. * OHSU demonstrated that ADT T deprivation alters hippocampus to sharply decrease two-minute word retention (short-term memory), resembling early Alzheimer’s or stroke. * Geriatric psychologist I consulted reports most of her ADT pts suffer dramatic to devastating emotional impacts, often a near absence of the emotions we want plus wide swings in the moods we don’t want; she regards ADT as primarily for patients who consider a heartbeat more important than QOL, who fear death above all, or who are encountering clinical failure. * “PC for Dummies” says ADT converts Mr. Nice to Mr. Extremely Irritable. I’m Mr. Irritable awreddy. * My survey of adjuvant ADT pts on alt.support.cancer.prostate => 14 respondents => 3 w/light SEs, 5 w/serious SEs, 6 w/devastating SEs; some of the latter – and their wives -- considered ADT worse than the alternative. * Typical IAD on/off cycle => 9-16 months on, 6-9 off, w/lingering SEs dominating off cycle => little SE break => low therapeutic index. * Antiandrogen SEs = primarily diarrhea (less w/Casodex) and breast pain . . . + maybe long term PC stimulation. * PCRI/Scholz: “The biggest difference between adjuvant treatments is QOL, not survival; choose by SEs.” BOTTOM LINE The few months adjuvant ADT MAY add to my life are highly likely be burdened with SEs which threaten the most important elements of my life. I’d far rather feel like an athlete, think like a student, and be a good companion to my wife for 5 years and then die than feel like road kill, think like a fencepost, and be a major PITA for 6 or 7 and die on her anyway. Life’s about quality, not just quantity, and the steeper the slide from vigor to rigor, the better. Besides, Partin says my glass is 1/6 to 2/5 full; I don’t want to poison it. MY PROPOSED PROTOCOL 1. Measure baseline biomarkers (e.g., PAP, CEA, NSE, CGA) to get some idea of heterogeneity/AIPC and thus likelihood ADT might help, then 2. WW, monitoring PC and CC as closely as is useful (e.g., biomarkers, creatinine, hypersensitive PSA plotted to distinguish trends from noise, bone scans (if informative), Octreoscans, any other CC markers.) for reliable indication of PSA DT, mets, and/or degree of heterogeneity, and 3. Enjoy high QOL until lab or symptoms indicate recurrence, then initiate treatment based on the treatment options available then. 4. In the meantime, consider A or B: A. Begin now with a low-SE PC therapy such as Casodex monotherapy, or B. Begin now with a low-SE protocol which fights both PC and CC, such as immunotherapy. Possibilities may include Provenge, Aptosyn, oncolytic viruses . . . QUESTIONS REMAINING Is my PC hormone-receptive (AD)? If ADT suppresses PSA, what drives IAD timing? What is my life expectancy and risk of recurrence without HT? With HT? Sketch my QOL curve with and w/o HT. Now add a time scale to QOL curve. Don’t PSA @ 6 months and PSA DT <12 months vs >24 months say much about prognosis, and thus the potential value of ADT, with little additional risk? Does all this alter your collective advice for immediate ADT? I would love to have the tumor board consider my rationale, because my overall threat is interdisciplinary. Feel free to omit the parts they haven’t time for, discuss relevant parts with them, and revise my suggested protocol collectively – if there’s anything here that hasn’t already been discussed. In fact, if the board is willing to discuss any of this WITH me, I can’t imagine a better opportunity for me to learn the fallacies in my facts or reasoning or to express my priorities, which probably differ from those of many other cancer patients. The board’s frank discussions of my morbidity and mortality risks would be welcomed, not feared. That’s not a naive presumption; I was told by a team of neurologists eight years ago that I had days – at best – to live due to what they presumed were brain stem emboli. I slept just fine that night, and was quite pleased when the MRI ruled that out. Caca pasa. When it does, we deal with it. And the more we know about a threat, the better we deal with it. Thanks. See you Friday Then there was more, some new and some incorporated above, but it never hurts to see/hear some of this complicated stuff twice: MY PRIORITIES Physical and mental vigor, zest for life, reasonable transition from vigor to rigor. There’s infinitely more to life than a heartbeat. My wife’s likely to lose me anyway at some point; why make her remaining years with me miserable, too, by exacerbating my irritability by making me miserable? Besides, she has both family and career support systems to draw on. From Strum: Commonly Reported Acute and Chronic Androgen Deprivation Syndrome (ADS) Symptoms [but charts don't work well in USENET] * => Unacceptable if pronounced and/or frequent Acute (symptoms in < 2 months) Chronic (symptoms in > 6 months) * Hot Flushes * Muscle atrophy in chest, arms & legs Impotence & loss of libido Atrophy of testicles * Aches & pains in joints * Decreased muscle strength & endurance * Loss of energy & “feeling weak” Weight gain due to increased body fat * Short-term memory difficulties Gynecomastia * Mood “swings” * Osteoporosis, progressive on CHB * Emotional changes (tearfulness, etc.) * Chronic fatigue-like syndrome * Anemia unrelated to blood loss, iron deficiency or bone marrow involvement Difficulty controlling blood pressure, often requiring initiation of changes in drug therapy Loss of blood sugar control in patients with diabetes mellitus * Alzheimer’s-like symptoms (severe short-term memory difficulties, inability to concentrate, etc.) Increase in urinary symptoms (urination or difficulty starting the urinary stream) * Increased serum cholesterol (LDL, or “bad” cholesterol) and/or & triglyceride levels HT < 12 mo => patients suffer typical acute ADS symptoms – invariably compromising healthy, active lifestyles -- but maybe not significant chronic symptoms. Chronic symptoms are much more prevalent with HT than is currently recognized, and some are nearly inevitable in patients treated > 12 mo. No, thanks, guys . . . I’ll take my chances, narrow down my choices, watch my PSA, and act if and when necessary. With any luck, my colon cancer or Meniere’s disease or a meteor will render my PCa moot before HT becomes the lesser evil. MY PROTOCOL PROPOSAL 1.WW, monitoring PC and CC as closely as possible (e.g., PSA, PAP, CEA, maybe hypersensitive PSA assay, any means of assessing androgen dependence, Octreoscans, . . . 2. Enjoy life until tests identify which threat looms larger. 3. Fight that threat. 4. If symptoms or that fight impact QOL, THEN consider ACS: Early vs. delayed treatment: Doctors don’t agree whether early HT helps with advanced but asymptotic PC. Their objection is to the SEs and the potential for HT-induced earlier refraction, and they believe HT should await symptoms. Walsh is in this camp. In a New Zealand trial, short-term neo-adjuvant CAB was not perceived by patients to be a major inconvenience. Compliance with short-term goserelin was excellent. POINTS TO BE INCORPORATED Decision factors from good sources (Walsh, Strum, PCRI ... Walsh sez wait until symptoms. Strum sez SEs/osteoporosis way underreported. Biomarker baselining and tracking important to determining degree of androgen independence. Factors favoring high androgen independence: Gleason > (3+3), aneuploidy, T3c, biologic marker elevation and/or heterogeneity in levels or ADT response. Baseline marker evaluation beyond PSA i.e. PAP, CEA, NSE, CGA is important especially in patients at high risk for AIPC. CC mets tend to kill much faster than PC mets, and carcinoid tumors > 2 cm have very high p(met). Young men with my numbers have unacceptably high relapse rates even w/local therapy + ADT. Rattle off some SE med SEs. ADT and Metabolic Syndrome The urology faculty of Johns-Hopkins publishes a quarterly Prostate Cancer Bulletin containing articles summarizing current PC topics. The current winter issue included the article, under this title, from which the following excerpts are taken FYI. Re hot flashes: they occur in 2/3 of men on chemical ADT but only half of men castrated for PC. THis implies to me that the drugs add their own hot flash risk above and beyond that of androgen suppression alone, and hot flashes may abate over time or continue for years. Those factoids address two questions we’ve often raised here. To the long lost of ADT SEs, the metabolic syndrome, which significantly increases the risks of heart disease deaths and diabetes, must now be added, according to the JNCI. The female hormone estrogen is regaining hormone-blocking favor in low doses because it is as effective as much more costly ADT drugs but doesn’t cause bone loss as the others do (and don’t forget that Fosamax is threatened with total recall). Total androgen blockade with antiandrogens is not thought to improve over ordinary LHRH adonists such as Lupron or Zoladex because adrenal androgens have little effect on the prostate. ADT very often leads to increases in abdominal fat, blood sugar, and triglycerides … components of metabolic syndrome, aka Syndrome X or insulin resistance. All this very significantly and directly contributes to heart disease, diabetes, and many other threats [which could become bigger problems than PC.] If your waist circumference exceeds your hip circumference, or if your waist exceeds 40 inches, congratulations; you’re officially obese. The extra belly fat is often both an indicator and a cause of insulin resistance or full-blown metabolic syndrome. While no studies prove that ADT causes metabolic syndrome, the connection looks and walks like a duck and recent evidence quacks. The next 14 pages are titled, “In-Depth Report: The Artificial Urinary Sphincter for Post-Prostatectomy Incontinence.” After that, some Q&A. Snippets include: SRT has only a 15% chance of helping after a G-7 case returns, because it’s likely to be distant. The ProtoScint Scan isn’t helping much in determining met location. [Walsh says seminal vesicle involvement and negative margins render SRT even less likely to help.] The admission criteria for J-H WW/AS/EM program includes Gleason < 7, < 3 of 12 positive biopsy cores, < 50% involvement in any core, PSA Density no more than 0.1, and no palpable DRE (T1C only). Johns Hopkins on ADT Excerpts from their “Health After 50” Medical Letter: Testosterone deprivation causes impotence, osteoporosis, and heart disease. Recent ADT cardiovascular studies have made doctors rethink who should pursue ADT. Without careful monitoring and preventive care, men > 65 on ADT for six months are at increased risk of heart attack. ADT bone loss will occur, especially during the first year. Get your BMD baseline measured before starting ADT, take 1-1.5 gms of calcium with Vit D daily, and perform strength training exercises to *reduce* bone loss. The extra threat of ADT probably overrides the increasingly strong and broad concerns about biphosponates such as Fosamax and its numerous problems such as brittle new bone layup. ADT initiates and/or enhances Type 2 diabetes or prediabetes within three months. This in turn increases risks of heart disease, vision loss, nerve damage, and maybe tumor growth. Obtain blood sugar and lipid profiles before beginning ADT and keep them up. Estrogen or progesterone work best to combat hot flashes, but should be reserved for severe cases of hot flashes. Libido and sexual function usually return within a year, especially in younger pts, after ceasing ADT. This can be mitigated by IADT, and is recommended for some pts with rapidly rising PSA but no mets. IADT may be as effective as continuous ADT, pending further research. Few men on such drugs as Lupron and Zoladex experience gynaecomastia, but men on antiandrogens such as Casodex frequently experience it significantly. ADT coincides with a peridontal disease risk increase from 4% to 80%. Get frequent, careful, focused dental care if on ADT. [Maybe that partially explains the increased CVD risk.] Anemia is common among men on ADT. One recent study shows that the ADT Syndrome, common w/ADT and including fatigue, depression, and trouble concentrating, may not result directly from ADT, but rather from T suppression, advanced age, advanced cancer, and/or psychological impacts]. Wives experience emotional impacts similar to and often stronger than their husbands on ADT … a good incentive to involve wives in our support programs. --------------- There's much more in this and my other computer, and it all came from many scores of Googled studies plus respectable websites. But I suspect this may keep you busy for awhile. I.P. >Here's the e-mail I sent my uro onc before our first serious ADT >discussion > three years ago. Maybe it will trigger some thoughts or >questions. If the acronyms throw you, ask; it was written for him and my >oncology team, not for patients. Thank you, I.P. This requires a slow and careful combing through. In the meantime, two comments and a question. You must know about the subject more than many run of the mill oncologists. (At least I'm not sure mine knows that much.) Secondly, you must've had an uncommonly close relationship w/ your oncologist(s). And the question: if you had to write and address the same dilemma today, three years later, what, if anything, would you have changed? SY > You must know about the > subject more than many run of the mill oncologists. (At least I'm not > sure mine knows that much.) One thing every patient knows -- after some serious self-analysis -- infinitely better than any onc is his own life's priorities. Only with those can a pt make an informed choice of treatments with SEs. Even bandaids have pros and cons, and it took an expensive trial to evaluate the tradeoffs of line vs no-line trifocals. That summary and its followups dramatically and unanimously changed my oncology team's treatment protocol for me and altered a couple of tenets in their whole PC treatment thought processes. It seems, for example, that the PC tx world presumed that every man placed potence at the top of his priority list. And even though that team's boss, Lange, was playing tennis a month after his RP, they didn't realize how many men actually value QOL very highly. Although many studies show that, it still doesn't sink in among people who don't have active lives. People like that will never understand how the toughest football player in the U.S. can cry for 20 minutes just because he's retiring from a *game*. > Secondly, you must've had an uncommonly > close relationship w/ your oncologist(s). Well, my wife and I do know my surg onc a) wears boxers, b) has a very active and meaningful sex life with his wife, and c) can't cure her incontinence in such activities as trampoline jumping (they have three children). What we don't know is whether (b) and (c) are related (it didn't occur to us to ask; maybe next time we confer ...) Also, neither my wife nor I is (are?) intimidated by people in white coats, so we feel and act pretty relaxed and informal around them. > And the question: if you > had to write and address the same dilemma today, three years later, > what, if anything, would you have changed? The short answer is that just in the past year alone, several new studies/medical articles addressing the ADT benefit-vs-SE tradeoff have graced these pages. 2-3 tilted towards earlier ADT, 3-4-5 tilted towards later ADT, if any, maybe even upon the appearance of symptomatic mets. Their common thread was the increasing recognition of ADT's QOL impact vs the widening debate over ADT's benefits. In balance, those new findings gave me more "I chose right!" moments than "Oh, crap" moments. The long answer will have to await my cursory examination of that loooong regurgitation I posted. I'll do that shortly, but not in the depth you might like, because better adjuvant treatments might mature before I actually need one so I'm not spending much time researching them now. I also think my previous computer may have a more succinct summary; I'll look. I.P. > I also think my previous computer may have a more succinct > summary; I'll look. Well, not so succinct, but this might keep you busy for a while. Another e-mail to my surg onc, from > 3 years ago: Today is my 24^th day on Zoladex. I’m due for a second injection this Friday if I elect to continue. SE status? I LOVE this T flare! It boosts my normally high mental and physical energy even higher. I decided to try ADT for a month based on assurance of three factors: 1. Representative SEs should surface, 2. 1/3 of pts have minimal SEs, 1/3 moderate, only 1/3 severe, and 3. It was winter, so the impact was negligible. However: 1. Astra-Zeneca says 2-4 weeks just for the T drop, Johns-Hopkins says “several weeks”, a professional discussion panel physician said his fatigue first struck months after beginning ADT, and Strum lists many major SEs that appear or become more severe after a year. The more I read, the worse this picture gets even though I’m looking for positives. 2. Strum reports that published, large-trial, severe SE likelihoods run 50-70-90%, “some are nearly inevitable in patients treated for longer than 1 year”, and “prolonged ADT may result in suppression of testosterone production as long as 24 months after discontinuation of ADT.” Also, only 28-month early ADT is proven to extend survival -- and by months, not years. 3. It’s spring; another injection plus its recovery time will impact this windsurfing season significantly, and I’m probably counting remaining seasons on one hand already. (If this sounds frivolous, realize that walking away from my engineering career for windsurfing in 1988 was and still is a no-brainer, partly in full, specific recognition that something like this may happen some day. I sail in 30-40-knot wind and chest-high waves 6-8-10 hours a day very frequently, and I know MANY windsurfers far more obsessed -- but with far less endurance -- than I. It would be a shame to change my paradigm now and give up that much adrenaline for a dubious, marginal, statistical benefit compounded by small bowel carcinoid.) Quoting Strum, “Even with a highly responsive physician knowledgeable about ADSyndrome, acute ADS-related symptoms invariably compromise the lifestyles of healthy and active prostate cancer patients.” And quoting George Carlin, “Life is measured not by the number of breaths we take, but by the moments that take our breath away.” I get those every windy day. I realize our ideal ADT goal is to eliminate every micromet while their numbers and volume are minimal. But isn’t that an extremely long shot, given that just one surviving micromet can finish me off when conditions allow it to bloom and spread? I feel GREAT, and I’m in no hurry to change that. My research this past month has reinforced my belief in the plan I e-mailed a month ago: 1. Postpone ADT while we monitor every useful PC and CC marker for threat assessment. 2. Keep looking for a protocol that fights both cancers with acceptable SEs (more below). 3. See whether I get past the two-year carcinoid recurrence threat peak with no CC or PC mets and a credible PSA DT > 24 months plus a raw PSA < 1.0. 4. Any recurrence before the peak two-year carcinoid mark will probably clarify and mandate a course of action. One nagging concern: I’ve felt no ADT downside yet. Is it possible my T is at castrate level yet I still feel this good? It’s slightly tempting to shoot up again IF my T is at castrate level, but I tend to believe it could not have plummeted yet, that there’s a locomotive coming around the bend with my name on it and a train of likely SEs in tow. My interest in preemptive ADT is waning with my reading rather than increasing just because SEs remain at bay. New sound bites and thoughts include: ** “The magnitude of [prostate tissue changes in response to ADT] is quite variable, with poorly differentiated, high-grade tumors responding the least to ADT. This seems to be the reason that 20% of pts respond poorly to hormone ablation.”* ** We see this everywhere: “hormonal treatments are palliative rather than curative”. So how is introducing debilitating SEs to an asymptomatic pt “palliative”? * ** From http://www.prostate-help.org/pohtwhen.htm : “*We do not believe that controlled clinical trials demonstrate clear advantages to hormonal therapy . . . [immediately] after RP with LN-negative disease or at the time of PSA elevation”. * RTOG 92–02 demonstrated that long-term ADT prolongs cause–specific survival^ in patients with locally advanced PC by [just] 3.4 %, and concluded that PC pts (100% in this trial) are willing to accept decreased survival in^ order to avoid the QOL consequences of long-term ADT.** * PC trials and knowledge are booming. We may know much more by the time biochemical or clinical failure catapults me across the fence. There’s also the risk that, on ADT, I may lack the stamina, mental acuity, and/or drive to research, assimilate, recall, and/or analyze PC literature effectively. I’m already swamped with the time this research is consuming; what good is extending my lifeline by 6-8 months if it’s all spent sitting here? No improvement in potence, maybe a little less incontinence, despite exercising both systems. Re: Avodart, Proscar, Actonel, et.al. I just haven’t had the time to research Proscar and Avodart (with or w/o Hytrin or Cardura) or SAB w/flutamide and finasteride to any conclusion. Those topics are diverging in complexity rather than converging to an opinion, but appeal to me more because of their possibility of greater therapeutic index (by my criteria). I hope to make more time to pursue those further and begin narrowing my focus by our Friday appointment. Then there’s the issue of bone resorption. Bone stabilization caught my eye, since it could help deter bone mets from both my cancers and offers several other benefits. Strum’s discussion of bone resorption, interleukin-6, Pyrilinks-D, free Dpd, etc., and Actonel sounded worth considering . . . until Actonel’s list of contraindications surfaced: GI sensitivity, GERD, dysphagia, ulcers, gastric pain, and PPIs. Been there, done those. However, the Actonel trials placebo control groups had just as many GI symptoms. Should we consider Actonel? I’d know pretty quickly if it’s upsetting my GI tract (as even cox-2 NSAIDS do within days). Alternatively, Strum highly recommends the bone supplements Bone Assure from Life Extension Foundation and Bone Up from Jarrow (I’d roll my eyes if these came from an ordinary website) and emphasizes their importance in bone physiology and their interactions with other cellular processes. Am I on a productive track? Can you help me focus these efforts? Other questions: Some PC pts monitor many lab parameters, including biomarkers and bone data. Are we missing something, or are those pts just clubbing gnats? Shouldn’t we establish a BMD baseline (with QCT?), given the likelihood that ADT will be necessary at some point? My BMD is likely to be high, given my lifetime of milk consumption and heavy exercise, so depletion may not be obvious without a pre-ADT baseline Shouldn’t we have irradiated my chest before starting ADT? Ditto finasteride, if we go that route? Could I get a copy of my post-op pathology reports from you and Dr. Wu? Strum: Chronic ADS symptoms are much more prevalent w/ADT than currently recognized, and some are nearly inevitable in patients treated > 1 year. Left untreated, chronic ADS is progressive with ongoing ADT and often leads to other medical complications. Me: There are some truly nasty, chronic mental and physical SEs on Strum’s menu --e.g., depression, hostility, muscle atrophy, chronic anemia and fatigue, osteoporosis, hypertension, Alzheimer's-like symptoms (severe short-term memory difficulties, inability to concentrate), elevated lipids. Even a subset of those is no way to live until the only alternatives are bone pain or not living. .............*AND MORE RESEARCH NOTES*: POINTS TO BE INCORPORATED A study è RP pts w/elevated PSA must weigh reduced QOL against the uncertain benefits. Median time met = 8 years following PSA elevation after RP + 5 yrs to death (No G# given) QOL impact not worth slight 5-yr CAB survival benefit. ACS, Jan 2005: Antiandrogen monotherapy no better than ADT1, sometimes less effective, has same SEs as ADT1. Unknown: optimal start & stop times, administration. Early vs. delayed ADT disagreement: Start when cancer reaches an advanced stage, or delay until symptomatic. Downside: SEs/QOL and possible accelerated refraction. Of 50,613 PC pts > 65 and over, those w/at least nine doses in the year after their diagnosis were 45 percent more likely to suffer a bone fracture than were those who did not receive the treatments. They also had a 66 percent greater risk of having a fracture that required hospitalization. [AND THAT’S MOSTLY COUCH POTATOES, I presume.] Recommended: biphoshonates. [see its SEs] > From http://www.prostatecancerupdate.net/2004/5/psa-progression.htm, (a meeting of top docs incl Lange) Dr. Roberts says: At PSA relapse I went on leuprolide, and that was the worst experience of my life because of the weakness and the chemical castration. The hot flashes were intolerable [and instantaneous], night and day; progesterone worked]. Weight gain and redistribution and athletic decline [were significant]. I developed a supraventricular tachyarrhythmia. So I stopped everything. After about five months I began to feel like a human being again. I had a very passionate relationship with my wife prior to all this, and then she became a good friend, sort of a buddy. I couldn’t stand that feeling. PSA is rising, but I won’t go back on leuprolide. I’d rather die. DR LANGE: I see it a lot, but I see more who say, “Ah, no big deal.” And I’ve never been able to postulate why that is. [Already couch potatoes, maybe?] DR FAGAN had terrible, horrible, awful, frequent hot flashes DR LONG takes Zoladex® , and after three months on Zoladex it hit him one day like a wilted plant. I started taking estradiol and all these things disappeared. Evidence suggests that early ADT may benefit the guys who have high-risk biochemical recurrence, delaying the development of bone metastasis; however, our follow-up was too short to show survival benefit. In the overall group of patients with PSA recurrence, we were not able to demonstrate any benefit. The doctors out there who are anti-early hormonal therapy can look at our data and say, “Ha! Told you so. There’s no benefit to early hormonal therapy.” On the other hand, for patients with high-risk disease, early hormonal therapy offers some benefit. clearly, you could tell the patients on Casodex because the gynecomastia was very obvious. My point is that Casodex is not without side effects. The other side of the LHRH story as far as side effects are concerned, having had my dad on it both long-term and now intermittently, is that some people really tolerate it exceedingly well. He virtually has no hot flashes. DR LOVE: Colleen, you were talking about gynecomastia. Could you comment on what methods can be used to decrease the chance of that happening? DR LAWTON: We can give low-dose radiation therapy preemptively to prevent gynecomastia from occurring. Once the gynecomastia has occurred, we can prevent it from getting worse. Often, we can eliminate the pain issues but we can’t reverse the gynecomastia, so if a patient is going to take Casodex 150, my bias is we ought to do it sooner, rather than later. Although [Dad] has bone mets, he has been asymptomatic from them. The toxicity he has experienced — lassitude and intellectual dullness — is not from the disease, but from the treatment. He’s a retired law professor and just can’t quite get things straight anymore. His weight is about the same, but his waist is about four inches bigger, so he’s gaining fat and losing lean body mass. The hot flashes are also an issue, although these have stopped now that he’s off Lupron. A lot of patients complain about the hot flashes. I assume we have the bone density loss pretty much under control, at least theoretically, with the bisphosphonates — provided patients receive them. I’m more concerned about how to deal with the day-in and day-out grinding-down effect of some of these drugs on a patient’s quality of life. He’s 78 now, but he was a healthy 72-year-old when he had his prostatectomy. He had recently retired and was very active, running daily and traveling a lot to visit my wife and me and the grandkids. At this point I wouldn’t call him housebound because he goes out and still drives, but a long trip is out of the question for him. He takes a lot of naps and has certainly given up all kinds of exercise. > From J-H White Paper 2005: HT is for men whose PSA doubles by 3 mo post-op. NO CONSENSUS on when to begin ADT. Whether it begins before or after positive bone scan may or may not affect survival. Yet early adjuvant ADT is increasing in popularity. T doesn’t drop until several weeks (one source says 2-3 weeks) after beginning LHRH analogs (e.g., Zoladex). Proscar (finasteride) and Avodart (dutasteride) are 5-alpha-reductase inhibitors; they block the conversion of T to DHT. SEs: some ED, some gynacomastia. Flutamide + finasteride has been studied for adv PC, but was less effective than an LHRH. 10% of pts keep their hot flashes after ADT. [Note: I'll take 6 months less heartbeat over many years of bad hot flashes, given what they do to my sleep.] PCRI: In summary, Scher et. al. recommend that a trial of AA withdrawal therapy is warranted in patients with relapsing prostate cancer prior to the initiation of more toxic therapy. The expected clinical response to AA withdrawal is correlated with a significant decrease in PSA levels usually occurring within several weeks of AA withdrawal and potentially lasting up to 1-2 years. AAWR after Casodex may take up to 4-8 weeks due to the long half-life of Casodex. Additionally, previous and future studies of prostate cancer relapse treatment with chemotherapy should be interpreted in light of these AA withdrawal response effects. Strum: The amount of cancer cell death from ADT in early-stage prostate cancer is usually dramatic. On rare occasions, no cancer at all can be found in the surgically removed prostate glands of men who underwent surgery after ADT. More typically, there is a drastic reduction in the number of cancer cells, but not total elimination. Androgen deprivation therapy also appears to have the ability to put some prostate cancer cells to “sleep.” What all this means is that the effect of ADT on different cells in a prostate cancer tumor can be variable; many of the cancer cells are killed, but others are simply inhibited from growing. In our practice, we stop ADT treatment after a year of therapy, except for ongoing suppressive therapy with Proscar or Avodart. Proscar and Avodart have minimal side effects, and we have found that they can be very effective at inhibiting the rise in PSA after the ADT has been stopped. We recently evaluated the results of using Proscar in our practice and found that men treated with Proscar remained off Lupron an average of three times longer then men who did not use Proscar. One concern that is repeatedly raised about the use of ADT for early stage patients is the potential for developing hormone resistance. Studies show that even when ADT is administered to patients with higher risk categories than IA, hormone resistance within five years of starting treatment appears to be a very rare event.15, 16, 17 *the magnitude of [prostate tissue] changes is quite variable, with high-grade tumors -poorly differentiated- responding the least to androgen suppression. This seems to be the reason for the 20% of patients not responding or having only partial response to hormone ablation.* * * *There is no question that hormonal suppression can be a very effective form of treatment for early stages of advanced disease. Even in very advanced disease, hormonal suppression can offer pain reduction and an improvement in the quality of life in those patients in which bulky tumors affect natural functions. There is a significant survival difference in advanced disease in relation to the number of metastatic lesions present. Labrie et al reported longer survival in patients with 1 to 5 bone lesions as compared to those with a higher number of bone lesions(16).* http://www.prostate-help.org/pohtwhen.htm CONCLUSIONS We do not believe that controlled clinical trials demonstrate clear advantages to hormonal therapy in the following scenarios: before RP, after RP with LN-negative disease or at the time of PSA elevation, adjuvantly with brachytherapy, or as primary treatment for localized or locally advanced disease. The evidence supports the use of adjuvant hormonal therapy in subsets of men undergoing external beam radiotherapy, but only in those with locally advanced or high-grade tumors, bulky but lowgrade tumors, and LN+ disease. Limited data suggest a possibility of a survival benefit for adjuvant hormonal therapy in the rare patient with LN+ disease after RP. The appropriate timing of hormonal therapy for patients with asymptomatic metastatic disease has not been determined. Much remains to be learned, including the most effective and best-tolerated androgen deprivation strategy and the appropriate timing of the institution of such therapy. In all settings in which androgen deprivation is used, the benefits must be weighed against the significant costs and toxicities, with particular consideration given to the expected length of exposure to hormonal therapy. Despite initial responses to monotherapy with medical or surgical castration, in most patients, distant metastatic disease will progress within 12 to 16 months. Low post-RP PSA => traditional recurrence tests are of limited help. CT scans and bone scans are not sensitive enough and ProstaScint to remains controversial and indefinitive. Most clinicians rely on the time to detectable PSA (within the first year or later) and the PSA doubling time PLUS those diagnostic studies to determine the likelihood of local vs. systemic failure . . . Of 304 patients w/detectable PSA relapse after surgery, 103 (34%) developed metastatic disease. The median actuarial time from PSA elevation to metastatic disease was 8 years with the median time to death following development of metastatic disease being another 5 years. [Post RT], emerging evidence suggesting that patients whose PSA values nadir at levels of 0.5-1.0 have a much lower chance of recurrence. > From AstraZeneca: ZOLADEX 3.6-mg formulation and the longer-acting 10.8-mg formulation are indicated for use in the palliative treatment of advanced carcinoma of the prostate. Chronic administration of ZOLADEX leads to sustained suppression of pituitary gonadotropins and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 2-4 weeks after initiation. ZOLADEX 3.6 mg and 10.8 mg are also indicated for use in combination with flutamide for the management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy. ZOLADEX 3.6 mg should be administered subcutaneously every 28 days into the upper abdominal wall using an aseptic technique under the supervision of a physician. While a delay of a few days is permissible, every effort should be made to adhere to the 28-day schedule. > From ASCO: Recommendations for the Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer They define Early deprivation therapy as initiation of ADT at diagnosis^ of metastatic or recurrent/progressive prostate cancer, deferred deprivation therapy as withholding ADT until the^ presence of clinical signs or symptoms. Overall survival (OS) was the primary outcome of interest; QOL hardly considered. *Loblaw, Mendelson, Talcott, et.al. * PURPOSE: To develop a clinical practice guideline for the use, combinations,^ and timing of various forms of ADT for the palliation of androgen-sensitive metastatic, recurrent, or progressive prostate carcinoma. (Attributes of good guidelines include validity, reliability,^ reproducibility, clinical applicability, clinical flexibility,^ clarity, multidisciplinary process, review of evidence, and^ documentation.)^ METHODS: An expert panel and writing committee systematically^ reviewed the literature, which included a search^ of online databases, bibliographic review, and consultation^ with content experts. A priori criteria were used to select^ studies for analysis and study authors were contacted when necessary.^ RESULTS: There were 10 randomized controlled trials, six systematic reviews,^ and one Markov model available to inform the guidelines.^ CONCLUSION: A full discussion between practitioner and patient should occur^ to determine which therapy is best for the patient. Bilateral^ orchiectomy or luteinizing hormone releasing hormone agonists^ are the recommended initial treatments. Nonsteroidal antiandrogen (e.g., Casodex)^ therapy may be discussed as an alternative, but steroidal antiandrogens^ (e.g., Cyproterone acetate, aka Androcur) should not be offered as monotherapy. Patients willing to accept^ the increased toxicity of combined androgen blockage for a small^ benefit in survival should be offered nonsteroidal antiandrogen^ in addition to castrate therapy. Until data from studies using^ modern medical diagnostic/biochemical tests and standardized^ follow-up schedules become available, no specific recommendations^ can be issued regarding the question of early versus deferred^ ADT. A discussion about the pros and cons of early versus deferred^ ADT should occur. For patients with documented metastatic disease, or whose clinical^ parameters suggest too small a chance for cure to justify the^ toxicity of extirpative therapy, systemic ADT through surgical^ or pharmacologic castration, antiandrogen therapy, or a combination,^ is the standard first-line treatment. The goal of ADT is palliation.^ However, there are considerable practice variations in the use^ of ADT in these situations. The possible explanations are numerous^ and include: the effectiveness of ADT in suppressing the PSA;^ the palliative nature of ADT; its cost and toxicity; the prolonged^ treatment required (further extended by PSA surveillance for^ biochemical recurrence); the highly variable time lag between^ initial PSA rise and symptomatic metastatic disease; and the^ sometimes conflicting results of clinical trials. Because the^ relative efficacy of alternative approaches to ADT appears small^ and its toxicity is substantial, patients may weigh the balance^ between the favorable and adverse consequences of palliative^ ADT differently. Therefore, shared decision-making between patients^ and their physicians is necessary for optimal use of ADT. Metastudy: early ADT for treatment of advanced PC reduces disease progression and complications. Early ADT MAY provide a small but statistically significant improvement in overall survival at 10 years. There was no statistically significant difference in PC-specific survival. But there were more frequent treatment-related adverse effects with early therapy. Additional studies are required to evaluate more definitively the efficacy and adverse effects of early versus delayed androgen suppression in men with prostate cancer. In particular trials should evaluate patients with advanced prostate cancer diagnosed by PSA testing and men with persistent or rising PSA levels following treatment options (e.g. radical prostatectomy, radiation therapy or observation) for clinically localized disease. Antiandrogen monotherapy is not recommended. Patients should be followed clinically and started on ADT once symptoms of locally progressive or metastatic disease present. Monotherapy with nonsteroidal antiandrogens^ showed equivalent survival compared to orchiectomy, but has^ less toxicity, particularly with respect to loss of libido and^ physical capacity. Steroidal antiandrogens have inferior time^ to progression of disease compared with LHRH agonists.^ *Nonsteroidal Antiandrogens (NSAA)* *Biologic rationale.* NSAA (flutamide, nilutamide, and bicalutamide) act to competitively^ inhibit androgen binding to receptors in target tissue. With^ therapy, a rise in serum testosterone is observed. NSAA are oral medications with reversible side effects once^ therapy has ceased. Bicalutamide has a half-life of approximately 1 week, allowing^ for once-daily dosing. Flutamide is more rapidly metabolized;^ the major active form has a plasma half-life of 5 to 6 hours,^ requiring drug-dosing three times a day. There have been no^ studies that have directly compared the different antiandrogens.^ In the meta-analysis (eight trials, 2,717 patients),^13 <http://www.jco.org/cgi/content/full/22/14/2927#R13#R13> wide^ overlapping confidence intervals are seen for the individual^ agents. Health-related QOL determinations were measured in patients^ with advanced prostate cancer on antiandrogens alone. Patients^ showed greater improvements in sexual interest and physical^ capacity (as a result of continued secretion of LH and higher^ testosterone values) when compared to medical or surgical castration^ in small RCTs.^27 <http://www.jco.org/cgi/content/full/22/14/2927#R27#R27> *Harms.* Overall, withdrawals due to adverse events occurred in 4% to^ 10% of patients (highest with flutamide, 9.8%).^43 <http://www.jco.org/cgi/content/full/22/14/2927#R43#R43> During single-agent^ therapy, significant gynecomastia and breast pain were reported^ (in up to 39% of patients). Hepatotoxicity has been reported^ with all NSAAs.^44 <http://www.jco.org/cgi/content/full/22/14/2927#R44#R44> * * *Steroidal Antiandrogens* *Biologic rationale.* Cyproterone acetate available in (Canada, Europe) is a steroidal^ antiandrogen with progestational properties (creating a feedback^ inhibition of pituitary LHRH release to suppress testosterone^ production) and direct effects on the androgen receptor.^ Tumor flare while initiating LHRH agonist therapy^ is reduced with cyproterone.^ *Harms.* In a phase III study of 525 patients, goserelin acetate plus^ cyproterone acetate was compared to cyproterone alone or goserelin^ alone.^46 <http://www.jco.org/cgi/content/full/22/14/2927#R46#R46> Goserelin was shown to be more effective than cyproterone^ alone in delaying the time to progression of metastatic prostate^ cancer (median time to progression of 225 days for cyproterone^ /v/ 346 days for goserelin; /P/ = .016). OS and CSS have not been^ reported for this trial. Although cyproterone acetate is generally^ well tolerated, liver toxicity has been recognized as a complication^ of long-term use.^47 <http://www.jco.org/cgi/content/full/22/14/2927#R47#R47> Edema, weight gain, and shortness of breath^ are rarely seen.^ Bottom lines, condensed: The central issue in the management of patients with progressive,^ recurrent, or metastatic androgen-sensitive prostate cancer^ is striking an appropriate balance between effective palliation^ and acceptable toxicity. Numerous randomized trials and meta-analyses^ have, at best, demonstrated small improvements, if any, in overall or^ cause-specific survival.^ An effective palliative treatment should improve or maintain, not degrade,^ QOL compared to no treatment. Many of the trials described above were performed at a time^ when QOL measurement was not well established nor recognized^ as being important. The Panel feels^ that the most pressing research need is to define the optimal^ time to initiate ADT. Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy. CONCLUSIONS: Subsequent nonsteroidal antiandrogen therapies were effective against prostate cancer relapse after hormonal therapy. The response to third line therapy was more effective and survival was improved from the time of first line therapy relapse among second line responders than that in nonresponders. Our data support the notion that second line responders are androgen independent but still hormonally sensitive. The three primary cancer recurrence factors were the time it took after surgery for the PSA to rise above zero, post-op PSA DT, and the Gleason score. The men with the highest risk were those with a high Gleason score, a rise of PSA within 2 years after surgery and a doubling of the antigen in less than 10 months. In about half of the cases, the metastases took 8 or more years to occur. In those cases where the spreading did occur the patients were still alive 5 years later. @ Stage D (confirmed mets), Van Aubel and colleagues^38 evaluated the results of immediate orchiectomy in patients with confirmed Stage D1 prostate cancer. Early hormonal therapy resulted in a 46% treatment failure rate after 45 months compared with shorter times to progression with delayed hormonal therapy, radical prostatectomy, and EBRT. In a retrospective study, Kramolowsky^39 analyzed 68 patients with Stage D1 disease, 30 of whom underwent immediate hormonal deprivation; the remainder received hormonal therapy when bone metastasis was diagnosed. At the 60-month follow-up, the median time interval to progression to bone metastasis was 100 months in the immediate hormonal deprivation group compared with 43 months in the delayed-treatment group. The immediate treatment group demonstrated a trend toward prolonged survival (150 months) compared with the delayed-treatment group (90 months). Vasomotor hot flashes are a common symptom in men who undergo androgen suppression therapy for prostate cancer. In a study of 63 men treated with orchiectomy or LHRH agonist, Karling and others^40 noted that 68% reported hot flashes and 48% still had hot flashes 5 years after treatment. The degree of distress experienced is variable, but for some men hot flashes are significantly bothersome that they seek intervention. Mayo Clinic conducted a cross-over study that randomized participants to receive megestrol acetate (Megace), 20 mg twice daily for 4 weeks followed by placebo for 4 weeks, or vice versa in a double-blind manner.^41 Sixty-six men with prostate cancer who had undergone androgen deprivation therapy and experienced bothersome hot flashes enrolled in the study. After 4 weeks, hot flashes were reduced by 85% in the treatment group compared with 21% in the placebo group. A follow-up to this study was conducted to determine the long-term effectiveness of megestrol acetate in the management of hot flashes.^42 Forty-five percent of those contacted were continuing to take megestrol acetate for 3 years or longer with continued control of hot flashes. Potential toxicities related to megestrol acetate were identified and include episodes of chills, appetite stimulation and weight gain, and symptoms of carpal tunnel syndrome. Fatigue is a common symptom in patients with cancer and may be multifactoral. It can have a profound effect on quality of life. Potential causes of fatigue include anemia, pain, inadequate nutrition, medication, inadequate sleep or rest, endocrine abnormalities, depression, and anxiety. In men taking androgen ablation therapy, fatigue seems to be a delayed rather than an immediate effect and variable in its severity. To offer the potential benefit of early hormonal therapy while minimizing its side effects, several novel methods of androgen ablation are currently under investigation. Sequential Androgen Blockade Sequential androgen blockade combines a 5 a-reductase inhibitor (finasteride [Proscar]) to reduce the conversion of testosterone to DHT and an antiandrogen to prevent residual androgen from reaching the androgen receptor. An example of such a regimen is finasteride, 5 mg twice daily, and flutamide, 250 mg every 8 hours.^66 Circulating testosterone is not reduced, thus minimizing the side effects usually associated with androgen suppression. Early results suggest that the time to progression is long, and the side effects are minimized compared with TAB.^67 Monotherapy The use of monotherapy with the pure antiandrogens is attractive because these drugs have the potential to preserve potency by maintaining serum testosterone levels. However, simultaneously, there is also the issue that maintained serum testosterone levels may reduce the effectiveness of prostate cancer treatment. This is related to the suppression of relatively androgen-insensitive clones in a heterogeneous prostate carcinoma, permitting androgen-sensitive clones to proliferate because of inadequate competition for the androgen receptor.^1 Flutamide has been evaluated as monotherapy is several Phase II studies, and clinical trials have used bicalutamide as monotherapy. Bicalutamide at a dose of 150 mg was found to be nearly equivalent to castration in patients with locally advanced disease.^70 Bicalutamide studies are ongoing with higher doses, 300 mg and above, to determine whether it is equivalent to castration in metastatic prostate cancer.^19 Thus far, antiandrogen monotherapy has not been shown to be equivalent to standard hormonal therapy with orchiectomy or LHRH analogues or to TAB in advanced prostate cancer.^1 Patients contemplating the potential risks and benefits of monotherapy need to understand that these uncertainties still exist. Preferences for short versus long - term *androgen* deprivation in *prostate* cancer survivors *D. Wilke, M. Krahn, P. Warde, A. Bezjak, G. Tomlinson, R. Rutledge and A. Detsky * Nova Scotia Cancer Center, Halifax, NS, Canada; University Health Network, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada Background: RTOG 92–02 has demonstrated that long-term^ *androgen* deprivation prolongs cause –specific survival^ in patients with locally advanced *prostate* cancer by 3.4 %.^ However, *androgen* deprivation decreases sexual function, reduces^ bone mass, and health - related quality of life. Methods: Patients^ with *prostate* cancer who received radiotherapy were presented^ with a scenario of Locally Advanced *Prostate* Cancer. We determined^ the minimally required increment in survival (MRIS) to accept^ LTAD (as opposed to STAD), using the Probability trade –off^ (PTO) technique. Utilities for impotence and osteoporosis associated^ with LTAD were determined using the Time trade –off (TTO)^ technique. The participants' current erectile function and *prostate*^ cancer –specific health –related quality of life^ were assessed using the International Index of Erectile Function^ (IIEF), and the Patient –Oriented *Prostate* Utility scale^ (PORPUS), respectively. Results: Sixty-seven patients were interviewed.^ The median age of participants was 72 (range 52 - 82). All participants^ were willing to trade survival in order not to have to undergo^ LTAD, compared to STAD. The median MRIS for *prostate* cancer^ –specific survival was 9.5%. Thirty percent of participants^ did not desire LTAD even if they were offered a 100% *prostate*^ cancer –specific survival. The median MRIS for *prostate*^ cancer –specific survival without an overall survival^ gain was 13% (the maximum trade off possible in the scenario),^ the mean being 9.75% [8.7 to 10.8%]. Median time willing to^ be traded off for impotence associated with LTAD was 2.5 years,^ corresponding to a median utility of 0.84. Median time willing^ to be traded off for osteoporosis associated with LTAD was 4.5^ years, corresponding to a median utility of 0.72. Multivariable^ linear regression of the MRIS for *prostate* cancer –specific^ survival revealed that age, IIEF sexual domain score, and having^ had bypass procedures were independent predictors of the MRIS^ for *prostate* cancer –specific survival. Conclusions: *Prostate*^ cancer patients are willing to accept decreased survival in^ order to avoid the quality of life consequences of long-term^ *androgen* deprivation.^ Baseline data for a prospective study of *androgen* ablation and quality of life *S. Gupta, F. Bylsma, J. Dignam, K. Kuball, W. Stadler and M. Rodin * University of Chicago, Chicago, IL 8210^ Background: *Androgen* replacement has been shown to improve cognitive^ & physical performance in hypogonadal men. Few studies have^ examined the effects of total *androgen* blockade on cognitive^ & physical performance of older *prostate* cancer pts. We^ report pre-treatment performance measures of an accruing cohort^ of men receiving anti-*androgen* therapy for *prostate* cancer.^ Methods: All *prostate* cancer pts (≥ 50 yrs) followed at the University^ of Chicago, starting *androgen* ablation are eligible. The CGA^ includes self-report measures for instrumental (household IADL)^ and basic (self care ADL) activities of daily living. Physical^ performance is measured by standardized directly observed tests^ including Berg Balance Scale (BBS) & Timed Up and Go (TUG).^ Cognitive measures include the Mini-Mental Exam (MMSE) &^ a comprehensive neuropsychological battery (tests of attention,^ fine motor, executive, verbal and spatial recognition, immediate/delayed^ recall). All scores are normed for age, sex and education. Pts^ are tested within 2 weeks of first treatment with planned assessment^ 6 mths and 1 yr later. Results: 12 pts have completed baseline^ evaluations. Ages range from 57–87 (mean 71 yrs). One^ pt self-reported impairment with one ADL. Directly observed^ physical performance yielded 7 of 12 men markedly impaired at^ baseline balance testing (BBS score < 40 suggests high fall^ risk) and 3 of 12 men at risk for falls based on TUG >13^ seconds. 4 of 12 men scored 22–25, (mild-moderately impaired)^ on MMSE. We predetermined cognitive impairment as scoring ≥2^ SD below the mean on at least 2 different domains assessed by^ the neuropsychological battery. 8 of 12 men met this definition.^ Verbal recognition (HTLV-R) and spatial recall (Rey Complex^ Figure Copy) were most often impaired. Conclusions: Clinically^ significant impairments in cognitive & physical performance^ are present at baseline in our older *prostate* cancer pts. As^ *androgen* blockade may cause further decrements in performance,^ identification of men who are at increased risk for treatment-related^ effects is imperative.^ Sequential Androgen Blockade Sequential androgen blockade combines a 5 a-reductase inhibitor (finasteride [Proscar]) to reduce the conversion of testosterone to DHT and an antiandrogen to prevent residual androgen from reaching the androgen receptor. An example of such a regimen is finasteride, 5 mg twice daily, and flutamide, 250 mg every 8 hours.^66 Circulating testosterone is not reduced, thus minimizing the side effects usually associated with androgen suppression. Early results suggest that the time to progression is long, and the side effects are minimized compared with TAB.^67 There are four marketed androgen antagonists. Three are non-steroidal and the fourth (cyproterone) is a steroid with mixed progestational and androgen antagonist activities and not approved in the U.S.. Of the non-steroids, bicalutamide is currently the biggest seller, probably due to its long half-life relative to flutamide, which facilitates once-per-day dosing. However, flutamide has recently come on the market as a generic in the United States, which is likely to significantly impact the future sales of bicalutamide here. Bicalutamide itself will come off patent in 2008. Nilutamide’s patent has also expired, but it was always a poor third to its competitors in terms of side effects and clinical use. Both currently used androgen antagonists, flutamide (Eulexin) and bicalutamide (Casodex), cause breast tenderness and gynecomastia, which limit their use for monotherapy. WHY? What’s the big deal, especially w/radiation? OTOH, androgen antagonist monotherapy, rather than CAB or antagonists in combination with orchidectomy, will likely see increased use, due to its relatively fewer negative effects on quality of life. Monotherapy The use of monotherapy with the pure antiandrogens is attractive because these drugs have the potential to preserve potency by maintaining serum testosterone levels. However, simultaneously, there is also the issue that maintained serum testosterone levels may reduce the effectiveness of prostate cancer treatment. This is related to the suppression of relatively androgen-insensitive clones in a heterogeneous prostate carcinoma, permitting androgen-sensitive clones to proliferate because of inadequate competition for the androgen receptor.^1 Flutamide has been evaluated as monotherapy is several Phase II studies, and clinical trials have used bicalutamide as monotherapy. Bicalutamide at a dose of 150 mg was found to be nearly equivalent to castration in patients with locally advanced disease.^70 Bicalutamide studies are ongoing with higher doses, 300 mg and above, to determine whether it is equivalent to castration in metastatic prostate cancer.^19 Thus far, antiandrogen monotherapy has not been shown to be equivalent to standard hormonal therapy with orchiectomy or LHRH analogues or to TAB in advanced prostate cancer.^1 Patients contemplating the potential risks and benefits of monotherapy need to understand that these uncertainties still exist. I.P. I just noticed something in that long research notes post that should make Mssr. Jordan quite happy, considering how badly he needed to know the name and source of the relapsed doctor whose ADT SEs drove him to abandon it. > > From http://www.prostatecancerupdate.net/2004/5/psa-progression.htm, (a > meeting of top docs incl Lange) Dr. Roberts says: [quoted text clipped - 9 lines] > friend, sort of a buddy. I couldn’t stand that feeling. PSA is rising, > but I won’t go back on leuprolide. I’d rather die. Glad to be of assistance, Steve. I.P. On March 11, Señor Freely wrote: > I just noticed something in that long research notes post that should > make Mssr. Jordan quite happy, considering how badly he needed to know > the name and source of the relapsed doctor whose ADT SEs drove him to > abandon it. (snip) I don't "badly need" anything from Mike. He was prepared to resume tx as necessary, but not to resume Lupron. Casodex, maybe. No one on the panel, including Dr. Roberts, could understand the rather extreme reaction he had. He joked that it was because he was so macho. So it's an interesting anecdote, maybe, but that's all it is. BTW, I Googled Alan Roberts, MD and of course found several. None of them are oncologists. Regards, Steve J Thank you, guys, for what you've posted so far. Lots of food for thought. In the meantime, a little update. This is verbatim from my local urologist: "I spoke to two of my partners who also cannot agree on optimal timing of hormonal ablation. However, the general consensus was that urgent hormonal treatment was not indicated, and that more data points were necessary (i.e. more PSA values). " SY (snip) > In the meantime, a little update. This is verbatim from my local > urologist: "I spoke to two of my partners who also cannot agree on > optimal timing of hormonal ablation. However, the general consensus > was that urgent hormonal treatment was not indicated, and that more > data points were necessary (i.e. more PSA values). " Caution! Urologists are essentially surgeons, and that's all they are. With some possible exceptions, they are not educated in the endocrine tx of PCa, which is what "hormonal ablation" is. I most urgently recommend consultation with a genuine cancer specialist, a medical oncologist; preferably one who is well-educated in tx of PCa. Some specialists can be found via this portal on the authoritative website of the Prostate Cancer Research Institute (PCRI): http://prostate-cancer.org/resource/find-a-physician.html Regards, Steve J "I believe it is a mistake for many urologists to be involved in the endocrine therapy of prostate cancer. Let me state why. Urologists are surgeons and many times surgeons rush to a treatment without really understanding what they are doing." -- Stephen B. Strum, MD Medical Oncologist PCa Specialist >Caution! > [quoted text clipped - 21 lines] >Medical Oncologist >PCa Specialist Yes, Steve, I realize that. After my local oncology consult on the 20th, I may take it upon myself to contact Dana-Farber. At the same time, neither of my urologists even suggested an oncologist consult at this point. If I didn't know better, I'd have been stuck w/ urologists. SY >> I most urgently recommend consultation with a genuine cancer specialist, >> a medical oncologist; preferably one who is well-educated in tx of PCa. [quoted text clipped - 10 lines] > this point. If I didn't know better, I'd have been stuck w/ > urologists. I fully agree that I don't want a dentist doing my RP or want a uro onc doing my ADT. I consulted uro oncs, a rad onc, and a med onc before my initial tx, and before I even considered post-RP ADT, my uro onc brought in a med onc for a long talk with both of them. Lots of diverse expertise, lots of publications and symposia, lots of research, and lots of clinical experience between the two of them, not to mention the rest of the team they represented. And I STILL didn't like their advice. By "like", I mean it didn't consider my own priorities very well, it contradicted some of my research, and it almost pooh-poohed SEs outright. They dismissed Strum's ADS work altogether for the same reasons they won't let him near symposia (lack of support for his claims). Sorry, but I am not willing to dismiss Strum's work so easily. I don't think a 28-day exposure to ADT drugs will paint an accurate SE picture (not counting osteoporosis, of course), for example. I have reached the admittedly arrogant but ever-stronger conclusion that no doc is going to convince me to accept or avoid any debatable and/or risky treatment for ANYTHING until and unless s/he either concurs with my research or explains any contradictions to my satisfaction. After three docs ignored my consistently rising blood glucose (even sustained prediabetic levels of 110-120 do a lot of permanent, serious, measurable, yet initially asymptomatic damage), I had to demand additional testing, including offering to pay for some of it out of my own pocket, to analyze and explain it more thoroughly and evaluate further measures. In another case an orthopedic said, "Your torn calf muscle will heal on its own in 6-8 months. Just baby it" Only when I inquired about physical therapy did he offer that PT could fix it right up in 2-3 months ... which it did. Few docs have the time or interest required to treat the *patient* rather than just the involved chunk of meat or bone. Many don't even have the required knowledge, sometimes even of some really basic stuff. I'm ever more leaning towards the studied opinion that the role of the average physician is to do the grunt work (e.g., surgery, prescriptions, procedures, referrals to the *good* (we hope) physicians) and add *suggested* factoids which need vetting before I add them to my list of decision points. If my eyes and brain and fingertips don't outlast the rest of my body, I fear the final years of my life unless I can find a gifted GP to oversee them. I.P. >I fully agree that I don't want a dentist doing my RP or want a uro onc >doing my ADT. I consulted uro oncs, a rad onc, and a med onc before my [quoted text clipped - 39 lines] > >I.P. I completely agree w/ you. It's scary how many people pick their physicians out of the Yellow Pages and then follow what they're told unquestioningly and obediently as if it's the Sermon on the Mount. SY > Lots of food for thought. Yikes. I hope you have a big appetite and a bottle of Maalox handy. '-) I.P. >> Lots of food for thought. > >Yikes. I hope you have a big appetite and a bottle of Maalox handy. '-) > >I.P. Indeed, I wish something entirely different was on the menu. SY >> Please don't hold back. > [quoted text clipped - 24 lines] > (I’ve researched medical issues on the web for many years and always > wear hip boots.) I. P. You've obviously thoroughly researched your options as objectively as is possible under the circumstances. This is clearly an area with few clearly established facts and many, many uncertainties. I wish I can do the same if I'm ever in a comparable situation. I would just like to make one comment which may not be too relevant for you, but may be for others. > MY STATUS > With my PC numbers, www.prostatecalculator.org from VA => 15% chance of > avoiding PSA failure for a decade. This calculator has come up before. In my case, pre-surgical PSA 4.5, post-surgical stage T2b, Gleason 7 = 3+4, it predicts a PSA non-recurrence rate at 7 years post surgery of 58 percent with the confidence interval being 49 percent to 68 percent. On the other hand, the Sloan Kettering calculator, with the same data predicts 96 percent with the confidence interval ranging from 88 percent to 100 percent. (The Sloan Kettering calculator lets you put in the number of disease free months since surgery, and I put that at 1 month. If I put it to 91 months, which is where I am now, it yields 99 percent at 7 and 10 years, with the range being 91 percent to 100 percent.) Note that these two estimates are not even within each others confidence intervals, so they can't both be caccurate. Of course, it is likely that neither is right and the truth is somewhere in between. But the Sloan Kettering is fairly consistent with other widely reported estimates such as that of Walsh, et. al. If anything the ProstateCalculator is the outlier. I can only conjecture about what may cause this discrepancy. It is generally true that any statistical estimate only applies to a population like the study population. For example, it is possible that the surgeons who performed the surgery for the ProstateCalculator population were generally much less competent than those who performed the surgery for the Sloan Kettering population. More likely, the methodology used by one or the other of the two studies is faulty. The ProstateCalculator study uses a statistical technique based on neural nets. I haven't investigated in detail how such things are used, but if they have any advantage over conventional statistical estimation techniques I imagine it would be in identify factors which play a significant role. But in this case, I don't see why standard techniques should not work. My guess is that the ProstateCalculator study was faulty either in its assumptions or how they were implemented. The bottom line is that I think that men with prostate cancer have to use such calculators with care and should rely on those strongly supported by several studies and by large populations. I think the Sloan Kettering calculator is probably one of the more reliable ones available online. It also allows you to enter more data. For example, you can enter the components of the Gleason sum and not just the sum. For example, the Sloan Kettering calculator gives different results in my case for Gleason 7 = 3 + 4 than for Gleason 7 = 4+ 3. 94 percent vs. 91 percent. > ADJUVANT TREATMENTS CONSIDERED > WW, ADT1,2,3 (early or at biochemical or clinical failure), IAD, [quoted text clipped - 331 lines] > > I.P. > I. P. You've obviously thoroughly researched your options as > objectively as is possible That elicited a smile, as what I've presented in this thread is far less than 5% of my volume of research. >> With my PC numbers, www.prostatecalculator.org from VA => 15% chance >> of avoiding PSA failure for a decade. [quoted text clipped - 15 lines] > Sloan Kettering is fairly consistent with other widely reported > estimates such as that of Walsh, et. al. I will eagerly try the S-K calculator again. I gave up trying to get it to work from my PC three years ago; maybe my Mac can access it. My surg onc is a S-K product, so he'd appreciate my loyalty. OTOH, VA stats, last I heard, constitute the most substantial body of PC data available, so if there's a problem, it may be, as you imply, in the analysis rather than the data base. OTOH, I don't really care a lot what my 10- and 15-year progs are. It wouldn't be likely to affect my choices, because so much will change by then. > The bottom line is that I think that men with prostate cancer have to > use such calculators with care and should rely on those strongly [quoted text clipped - 5 lines] > my case for Gleason 7 = 3 + 4 than for Gleason 7 = 4+ 3. 94 percent vs. > 91 percent. A distinction which, IMO, is of no practical use. Give me a huge, well-designed, peer-reviewed, scientific study with a 40-50% difference between tx outcomes and I might consider it useful, but I can always find better decision foundations than mere 5% or 20% -- or seven-month -- outcome differences. I.P. Here are the six questions I've come up with so far and I still have a day or two to fine-tune it. (1) Do my PSA results since Sept. 2007 represent an actual biochemical recurrence or could it be a late "bounce"? (2) If it's not certain, how should I be monitored in the future? (3) If it's a recurrence, how aggressively should I proceed? (It's my impression that the above-mentioned authors advocate WW w/ PSADT values similar to mine.) (4) If I proceed w/ ADT, what are the best ways to minimize/address SEs and maintain QOL? (5) What do I gain (in years of life, etc.) by proceeding aggressively at this point? What is your understanding of the literature in this regard? (6) Would you suggest I contact Dana-Farber for their opinion? Please suggest any additions or deletions and critique mine mercilessly. Note that this is my first meeting w/ the guy, so, on one hand, I don't want to overwhelm him, OTOH, I want us to get straight to the point. In the email, I'm going to mention nothing of my Hx counting that he'd have a copy of my chart before the appointment. SY > Here are the six questions I've come up with so far and I still have a > day or two to fine-tune it. [quoted text clipped - 10 lines] > (4) If I proceed w/ ADT, what are the best ways to minimize/address > SEs and maintain QOL? Good questions. I think I know the answers, but it's good that you hear it from an oncologyst. But, #4 may be a little out of order. Your next step is likely EBERT or IMRT, not ADT. > (5) What do I gain (in years of life, etc.) by proceeding > aggressively at this point? What is your understanding of the > literature in this regard? He can't answer this one, but recent studies seem to indicate it is significant. Having said that, remember that I don't believe your recent PSAs indicate that any treatment is indicated. > (6) Would you suggest I contact Dana-Farber for their opinion? You might want to ask about supplements. Vit C, D, & E, capsacin, sellenium, lycopene, green tea, etc. Again, we hash these out pretty good around here, but it's always nice to here confirmation and denial.  SignaturePSA 16 10/17/2000 @ 46 Biopsy 11/01/2000 G7 (3+4), T2c RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins PSA <.1 <.1 <.1 .27 .37 .75 PSAD 0.19 years EBRT 05-07/2002 @ 47 PSA .34 .22 .15 .21 .32 PSAD .056 years Lupron 07/03 (1 mo) 8/03 and every 4 months there after PSA .07 .05 .06 .09 .08 .132 .145 PSAD 1.4 years Casodex added daily 07/06 PSA <0.04, <0.05, <0.04, <0.04, <0.1 2/12/08 Non Illegitimi Carborundum >Your next step is likely EBERT or IMRT, not ADT. That step has already been taken in the fall of 2005. SY >>Your next step is likely EBERT or IMRT, not ADT. > > That step has already been taken in the fall of 2005. Then disregard my last few emails. I thought that you were about to go with EBRT in May 2005, but cancelled. That being the case, if and when your PSA goes up to 0.2 or 0.3 or so, you onc may recommend ADT. But, probably not until it goes higher. > Here are the six questions I've come up with so far and I still have a > day or two to fine-tune it. > > (1) Do my PSA results since Sept. 2007 represent an actual > biochemical recurrence or could it be a late "bounce"? Not having a record of those results, it's not possible to guess. And a guess would be the most that we laymen could do. I think that that is a question for a well-trained oncologist. > (2) If it's not certain, how should I be monitored in the future? Some say 90 day test cycle using less-sensitive test protocols, others say monthly using ultra-sensitive protocols. Like just about everything else in this affair, there is no agreement. I recommend selecting what's comfortable. > (3) If it's a recurrence, how aggressively should I proceed? (It's > my impression that the above-mentioned authors advocate WW w/ PSADT > values similar to mine.) I would recommend hitting it hard and early. > (4) If I proceed w/ ADT, what are the best ways to minimize/address > SEs and maintain QOL? Please refer to my responses of a few days ago on the thread "Androgen Deprivation Syndrome." > (5) What do I gain (in years of life, etc.) by proceeding > aggressively at this point? What is your understanding of the > literature in this regard? No one can decide that except the patient, after having educated himself via objective references. And even those are hardly better than guesses, IMO. There are over 2300 relevant abstracts on Pub Med. Go to www.pubmed.gov and search on "prostate cancer quality of life." Pub Med is a service of the U.S. National Library of Medicine and the National Institutes of Health. > (6) Would you suggest I contact Dana-Farber for their opinion? Questions can be asked, but I understand that the medic to be seen is a urologist. I have previously made my recommendation about uro vs. oncologist. Good Luck! Steve J "As a physician, I am painfully aware that most of the decisions we make with regard to prostate cancer are made with inadequate data." -- Charles L. "Snuffy" Myers, MD Medical oncologist. PCa survivor. >Questions can be asked, but I understand that the medic to be seen is a >urologist. I have previously made my recommendation about uro vs. >oncologist. I must have not been clear. The physician to be consulted with is a medical oncologist, NOT a urologist, and the questions are meant to be for him to respond to. With that clarified, would your reaction to the questions be different? SY Quoting me >> Questions can be asked, but I understand that the medic to be seen is a >> urologist. I have previously made my recommendation about uro vs. >> oncologist. He replied: > I must have not been clear. The physician to be consulted with is a > medical oncologist, NOT a urologist, and the questions are meant to be > for him to respond to. With that clarified, would your reaction to > the questions be different? Aha. Yes indeed. In that event, I recommend making sure that a complete clinical record is available to the onc (radiation or medical? Different subspecialties). Then have an agenda ready for him to see, even before he comes into the exam room. What I do, which seems to work, is to give my agenda, latest PSA graph and current med list to the receptionist when I check in. They go to my onc along with my chart. She's ready with responses when she comes in. Put that agenda together well in advance and revise it as ideas occur. Please let us know how it goes. Regards, Steve J >In that event, I recommend making sure that a complete clinical record >is available to the onc (radiation or medical? Different [quoted text clipped - 8 lines] > >Please let us know how it goes. Thanks, Steve. I was told that they got my record from the urologist's office. As to giving him my agenda prior to the consult, that is the whole point of these questions that I wanted your feedback on -- to email them to the onc PRIOR to the consult. SY > (4) If I proceed w/ ADT, what are the best ways to minimize/address > SEs and maintain QOL? > > (5) What do I gain (in years of life, etc.) by proceeding > aggressively at this point? What is your understanding of the > literature in this regard? I'd do my own research first to give myself some idea of how straightfoward and thorough he's being. I.P. >> (4) If I proceed w/ ADT, what are the best ways to minimize/address >> SEs and maintain QOL? [quoted text clipped - 7 lines] > >I.P. To be honest, I don't think I, within a very short period of time, can bring myself to the same degree you and other posters here have familiarized yourselves w/ voluminous research. But from what I've read here over and over my understanding has been that there was no agreement in the field of oncology as to when to begin ADT. Is it realistic to expect a definitive answer when there appears to be a consensus that it doesn't exist? All I can ealistically expect is merely another opinion. SY > Is it realistic to expect a definitive answer when there appears to be > a consensus that it doesn't exist? All I can ealistically expect is > merely another opinion. > > SY At this point, your onc is not likely to recommend ADT. SignaturePSA 16 10/17/2000 @ 46 Biopsy 11/01/2000 G7 (3+4), T2c RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins PSA <.1 <.1 <.1 .27 .37 .75 PSAD 0.19 years EBRT 05-07/2002 @ 47 PSA .34 .22 .15 .21 .32 PSAD .056 years Lupron 07/03 (1 mo) 8/03 and every 4 months there after PSA .07 .05 .06 .09 .08 .132 .145 PSAD 1.4 years Casodex added daily 07/06 PSA <0.04, <0.05, <0.04, <0.04, <0.1 2/12/08 Non Illegitimi Carborundum Guys, May I respectfully ask you to focus on whether the questions themselves make sense? We can process his responses, whatever they might be, next weekend, Thanks. SY > Guys, > > May I respectfully ask you to focus on whether the questions > themselves make sense? We can process his responses, whatever they > might be, next weekend, Thanks. Those are all valid questions. I.P. > Guys, > > May I respectfully ask you to focus on whether the questions > themselves make sense? We can process his responses, whatever they > might be, next weekend, Thanks. My comments, aside from the EBRT / IMRT are unchanged. The questions are good, IMHO, and the only ones I would add would be regarding supplements. SignaturePSA 16 10/17/2000 @ 46 Biopsy 11/01/2000 G7 (3+4), T2c RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins PSA <.1 <.1 <.1 .27 .37 .75 PSAD 0.19 years EBRT 05-07/2002 @ 47 PSA .34 .22 .15 .21 .32 PSAD .056 years Lupron 07/03 (1 mo) 8/03 and every 4 months there after PSA .07 .05 .06 .09 .08 .132 .145 PSAD 1.4 years Casodex added daily 07/06 PSA <0.04, <0.05, <0.04, <0.04, <0.1 2/12/08 Non Illegitimi Carborundum > To be honest, I don't think I, within a very short period of time, can > bring myself to the same degree you and other posters here have [quoted text clipped - 5 lines] > a consensus that it doesn't exist? All I can ealistically expect is > merely another opinion. Excellent points all. But I wasn't so much suggesting you dig through the medical literature, rather just reading the ADT chapters of some of the PC books, browsing the ADT and HT threads here, reading whatever you can stomach of my condensed posts in this thread, and reading Strum's ADS tomes. A day or three of that will help you find both extremes and a midpoint from which you can evaluate your med onc. If by that time s/he's still way ahead of you, you probably have a keeper who may save you a great deal of future second-guessing. Besides, when to start ADT is just one of many issues to consider. I.P. > Now to where I'd like an input from all of you who are familiar w/ the > post-radiation recurrence,and/or pro- and con- ADT issues, and other [quoted text clipped - 4 lines] > spent productively, not just like, "Big Daddy. please tell me what to > do." I agree that you should have another PSA in 6 months and, if it's still far less than 0.10, take it to the next 6 months. As to ADT. Virtually every man who undergoes treatment involving current ADT meds will experience some issues that they have never dealt with in their lives. Some will be mild. Some will be moderate but might be made mild with other meds. Some will be serious but might be made moderate with other meds. Some will be so strong that a few will stop using them though they may die sooner. But, nobody knows how many or which SEs he will experience or how severe they will be or how easily they can be mitigated by other medications or activities. For a good list of SEs, please check out: http://www.prostate-cancer.org/education/sidefx/Strum_ADS.html I honestly don't think you are anywhere near chemo yet, but it is possible your onc may know of a study that usese a combination of ADT and chemo for a surprise attack on the cancer. > Hi, guys. First of all, a little update. My original, high-power > Houston urologist responded to my question about my three recent [quoted text clipped - 16 lines] > > SY Sy - don't know your numbers, psadt plays a big factor, not to mention your other stats gleason, age, other health, tolerance for potential se's etc. IP (& others) surely provides much food for thought. Due to my gleason (3+5) and quick relapse afer my RP (12-05) then little lack of much of a sustained drop from SRT (5-06) I chose treatment to at least arrest the spread. There are clincal trials that have chemo & ADT2 (MSKCC- http://piurl.com/Ai 0 as well anti-angiogensis trials with ATN224 (MSKCC , I think Yale too) and Johns Hopkins has Revlimid. Some these while phase 2 trials and being more experimential may de worth inquiring about may have less SE's than adt / chemo. Good luck. I believe those calculators are more for stress relief than anything else. I punched my brothers numbers in and came out with 99's and 10 yr. number 96. His numbers going in were PSA 6.1, Gleason (3+4)=7, path. (3+5)=8, RP in 1999, 84 months undetectable, extra capsular extension. His cancer returned with a vengence 10 months after last undetectable at a 1.3 and is doubling every 3.1 months. He will be starting triple blockage in the near future probably with Trelstar+ Casodex+ Advodart as recommended by Dr. Strum. Ron S. -- Message posted using http://www.talkaboutsupport.com/group/alt.support.cancer.prostate/ More information at http://www.talkaboutsupport.com/faq.html > I believe those calculators are more for stress relief than anything else. > I punched my brothers numbers in and came out with 99's and 10 yr. number > 96. His numbers going in were PSA 6.1, Gleason (3+4)=7, path. (3+5)=8, RP > in 1999, 84 months undetectable, extra capsular extension. His cancer > returned with a vengence 10 months after last undetectable at a 1.3 I fail to see how one slight departure (failure at 9 years rather than 10) from the expected value, especially given its 8% error window, renders their statistics invalid. If they expected EVERYONE to remain disease free at 10, the number would be 100%, not 96, and the accuracy figure (1 sigma, I suppose) would be +/- 0 %. I.P. I agree with your rational, however, it is amazing how many people don't beat the odds given how great they are. I can't help but think of how many people have been told that they are "cured" after 5 years or 7 years or even 10 years with undetectable psa. Also how many treatment options are based upon these same cure rates for the purpose of selling a particular option only to find out later down the road that they weren't cured after all. I believe these numbers for success rates are inflated as a result of many older men dying of something else before their cancer recurred. Those additional numbers would not be included as recurrence and therefore would result in an inflated success rate. How many men that die of other causes actually have autopsies. Ron S. -- Message posted using http://www.talkaboutsupport.com/group/alt.support.cancer.prostate/ More information at http://www.talkaboutsupport.com/faq.html Sy, are you in or around Houston? Gourd Dancer > Hi, guys. First of all, a little update. My original, high-power > Houston urologist responded to my question about my three recent [quoted text clipped - 16 lines] > > SY >Sy, are you in or around Houston? > >Gourd Dancer I was in and around Houston for 23 years and moved up north in 2000, a month after my RP. I used to know the medical community there fairly well. SY |
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