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Medical Forum / Diseases and Disorders / Prostate Cancer / March 2007Prostate Cancer Survival Worse After Radiation
Prostate Cancer Survival Worse After Radiation Than Other Modalities March 9, 2007 ? A new analysis that compared 3 common treatment options for prostate cancer found a difference between them. Men who were treated with external-beam radiotherapy did not live as long as those who had radioactive seed implants or those who opted for surgery. "This is the first study to look at a hard end point of overall survival, and it did find a difference between the treatment modalities," commented lead author Jay Ciezki, MD, radiation oncologist from the Cleveland Clinic, in Ohio. "Previous studies have looked at the softer end point of biochemical relapse and showed equivalence." Dr. Ciezki presented the results at the recent Multidisciplinary Prostate Cancer Symposium in Orlando, Florida, which was cosponsored by the American Society of Clinical Oncology (ASCO), the American Society of Therapeutic Radiology and Oncology (ASTRO), and the Society of Urologic Oncology (SUO). The analysis involved 2285 men treated at the Cleveland Clinic between 1996 and 2003. "The majority had low-risk or intermediate-risk prostate cancer, which accounts for 80% or more of the prostate cancer cases that we see," Dr. Ciezki commented. Nearly half of the men (1053) had undergone a radical prostatectomy, 662 had radioactive seed implants, and 570 men received external-beam radiation therapy. The median dose of radiation was 82.0 Gy (range, 68.4 ? 82.9 Gy). The researchers controlled for a large variety of factors that are thought to influence overall survival, including age, comorbidities, cardiovascular health, body-mass index, socioeconomic status, initial prostate specific antigen (PSA) level, biopsy Gleason score, clinical stage, use of androgen deprivation and duration, smoking history, and alcohol use. Dr. Ciezki noted that smoking had a significant negative effect on survival in these patients, and the size of that effect was "very profound." Overall Survival Worse after External-Beam Radiotherapy The 5-year overall survival was 93.8% in men who had external-beam radiation, compared with 95.7% in those treated with radioactive seed implants and 97.7% in those who had surgery. After researchers controlled for confounding factors, the radioactive seed implants and surgery were found to be equally effective, while external-beam radiation remained less effective. "These findings indicate that the 3 major forms of treatment for early-stage prostate cancer are not necessarily equivalent in terms of overall survival," Dr. Ciezki told journalists. "We are reporting that we have found a difference. The next step is to investigate why there is a difference between the modalities," he said. Multidisciplinary Prostate Cancer Symposium: Abstract 293. Presented February 24, 2007. ... > Overall Survival Worse after External-Beam Radiotherapy > [quoted text clipped - 4 lines] > found to be equally effective, while external-beam radiation remained less > effective. ... I'm becoming pretty jaded with published medical research. Although the sample size in this study was pretty large, the measured effect here is at least in _prima facie_ contradiction to other studies which have shown that external beam is more effective than brachytherapy alone in controlling intermediate and high risk cancers. We also know that the populations selected for each type of therapy are typically different. Surgery tends to be performed on lower age men, brachytherapy (as a monotherapy at least) on lower risk men, and external beam radiation on men with greater age and risk factors. So a great deal depends on how accurately the researchers controlled for "confounding factors". I posted a message to sci.med.prostate.cancer about an interesting review of medical research that claimed that 89%(!!) of published articles in medical journals claiming some "statistically significant" difference between two populations turn out to have no difference when further, more extensive research is done. See: http://tinyurl. com/ytnx4b. Alan > ... >> Overall Survival Worse after External-Beam Radiotherapy [quoted text clipped - 30 lines] > > Alan It is a truism that one should not draw a conclusion based on a single study. Researchers do the best they can to account for any systematic biases, but they can't eliminate those they don't fully understand. Even in the best of circumstances, using conventional confindence intervals, a certain small percentage of studies will produce misleading results, just by chance. I would be surprised in the figure for unconfirmed studies was as high as 89 percent, but anything is possible. Perhaps someone should analyze those results again to see if that study has a systematic bias. There is an extra space in the link. It should be http://tinyurl.com/ytnx4b Also it would be helpful to get a link to the actu al study rather than alan's summary. >> ... >>> Overall Survival Worse after External-Beam Radiotherapy [quoted text clipped - 48 lines] > Also it would be helpful to get a link to the actu al study rather than > alan's summary. I found the video which you referenced at the above site. It was fascinating. It showed the complexity of biomedical research. He didn't actually say that close to 90 percent of all studies were not borne out by later work. If I understood correctly, that was the number which found 'statistically significant' results. He goes on to question that and says it is important that a study be credible in addition to statissfying various reigorous statistical standards. It is too easy for studies to have unexamined biases. He says a lot more also. I think any lay person should not jump to conclusions from the video because there is clearly a lot going on there that depends on context and not being experts ourselves we probably can't really evaluate the meaning of what he says. My feeling is that you have to look carefully at exactly what any study did. There is a tendency to generalize from the study population to the general population and to situations which may differ in important respects. Such generalization may not be valid. > >> ... > >>> Overall Survival Worse after External-Beam Radiotherapy [quoted text clipped - 66 lines] > general population and to situations which may differ in important > respects. Such generalization may not be valid. Leonard, Sorry about the misunderstanding of the 89%. One of the problems with a video, as opposed to a paper, is that you can't easily "re-read" parts to figure out what it said. I did find a paper by Ioannidis that contains some of the material that went into his talk. It's an open journal paper at with the interesting title of "Why Most Published Research Findings Are False". See: http://tinyurl.com/ceq33 for the full text. I hope Google doesn't mangle that URL. The math in the paper is over my head, but you may be able to evaluate it and let us know what you think. Thanks. Alan > Prostate Cancer Survival Worse After Radiation Than Other Modalities > [quoted text clipped - 3 lines] > in Ohio. "Previous studies have looked at the softer end point of > biochemical relapse and showed equivalence." I find it, well, disconcerting when researchers who should know better make false claims. Dr. Ciezki's (currently unreviewed and non-journal published) study was not the first (nor the second, third, fourth or fifth) to compare treatment modalities using survival as the endpoint. I guess I prefer to think he is just "grandstanding" in order to increase his chances for future grant funding, rather than to assume he is, well, one brick short of a load. Previous references follow...ron The following long-term studies compare RP, RT and WW: Urology. 2006 Dec;68(6):1268-74; Long-term survival probability in men with clinically localized prostate cancer treated either conservatively or with definitive treatment (radiotherapy or radical prostatectomy); Tewari A, Raman JD, Chang P, Rao S, Divine G, Menon M. J Urol. 2007 Mar;177(3):911-5; Long-term survival in men with high grade prostate cancer: a comparison between conservative treatment, radiation therapy and radical prostatectomy--a propensity scoring approach; Tewari A, Divine G, Chang P, Shemtov MM, Milowsky M, Nanus D, Menon M. J Urol. 2007 Mar;177(3):932-6; 13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort; Albertsen PC, Hanley JA, Penson DF, Barrows G, Fine J. The following reference compares RP and RT: J Clin Oncol. 2003 Jun 1;21(11):2163-72; Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era; D'Amico AV, Moul J, Carroll PR, Sun L, Lubeck D, Chen MH The following reference was a non-reviewed AUA presentation: American Urological Association Annual Meeting; May 21 - 26, 2005; San Antonio, Texas, USA; Publishing #: 468; Presentation Title: HIGH GRADE PROSTATE CANCER: WHAT IS THE BEST TREATMENT APPROACH?; Category: 39 Epidemiology and Natural History; Author Block: Ashutosh Tewari*, New York, NY; Ram Dasari, Detroit, MI; Assaad El-Hakim, New York, NY; George Devine, Detroit, MI; M Mendel Shemtov, New York, NY; Christopher R Porter, Seattle, WA; Eduard J Gamito, Peter N Schlegel, New York, NY; Mani Menon, Detroit, MI 1. The overall survival difference is very small. We are talking just 7 more deaths in the RT arm (cause of death not defined). 2. This is an observational study (not a randomized study) and just an oral presentation at a conference. Not much peer review. 3. Treatment period is 1996 to 2003. Were more RT patients treated in the 90s as compared to brachy patients treated in the 2000s? Was the RT treatment not as targeted as is presently available? 4. Why no mention of cause of death and disease-specific mortality? 5. The median RT dose of 82.89 Gray seems extremely high (for the study period). Is it possible that scattered radiation from such high dose could be a cause of death? Hard to understand why this study was even done. More so when survival is so close for all modalities and so much important data omitted ... Ron's conclusion must be on the money! > 1. The overall survival difference is very small. We are talking just > 7 more deaths in the RT arm (cause of death not defined). [quoted text clipped - 11 lines] > is so close for all modalities and so much important data omitted ... > Ron's conclusion must be on the money! The problem Ron pointed out, namely that the author is claiming his study is the first of its kind when it is not, is a bad sign. It either indicates that the author did not search the literature before publishing, or that he is cavalier with the facts while boosting his own ego. The problems you point out also seem to be telling. The magnitude of the effect is pretty small in a pretty large population - all measured at one institution. As Ionnadis pointed out (see the citation in my posting above in response to Leonard), as the measured effect gets smaller the chance that it is real also gets smaller. The fact that a large number of "confounding factors" also had to be accounted for with many adjustments to the data offers that much more opportunity for error. The question of effectiveness of radiation vs. surgery is a tough one to evaluate. Most of us have an emotional investment in the answer, not wanting to hear that our own treatment (radiation in my case) is not as good as one we didn't get. Ron has taken some hits from emotional responses to his postings because of this. I think there's also a lot of comparable bias by the investigators. If we did a study of studies conducted by surgeons vs. studies conducted by radiation oncologists I'd bet money we'd find a "statistically significant" difference between their reports - probably a very large one. Alan > I think there's also a lot of comparable bias by the > investigators. If we did a study of studies conducted by [quoted text clipped - 3 lines] > > Alan The patient centered thing is also important. Radiation was not initially offered becasue it was so much better than surgery. It was just less invasive, you din't have to miss work nor sit around in a hospital for a month and so forth. The patients may like such quality of life at the time they are being treated choices. Not so much which is better like a bar room comparison, but which is better for me given that I don't want to miss out on doing what I am doing and so forth. A new thing like tookad, for example, using light located by a chemical which finds the place to heat up is not being marketed because it will prolong the life of the patient. I think it is being offered becasue it has less SEs: less discomfort of treatment, not much time, and other existential QoL advantages to offer the patient. I would also would like to point out that if you read the lionities sp (not only can't be pronounced it also can't be spelled ;) piece you should also read the erudite comments by the peers who disagree with him for various reasons. > The patients may like such quality > of life at the time they are being treated choices. Not so much which [quoted text clipped - 5 lines] > it has less SEs: less discomfort of treatment, not much time, and > other existential QoL advantages to offer the patient. So do aspirin, voodoo, and wishful thinking . . . right up until they KILL ya. Anybody more concerned about a month of hassles than the potential for a complete cure is living on a different planet than most of us. I.P. > So do aspirin, voodoo, and wishful thinking . . . right up until they > KILL ya. Anybody more concerned about a month of hassles than the > potential for a complete cure is living on a different planet than most > of us. > > I.P. If one treatment is as good as the other, and science can not say which is better, fill in blanks with whatever metaphors suit your insults... But we can't discouunt science because of a statistical nit picker nor someone out to make a buck pushing their bias for every buck they can get; and I'm excited about new developments and new directions and possible this and maybe that because I only a have a little while left to live the way things stand now. Actually, forget about it, I don't have time for this--you win On Mar 23, 1:44 pm, aper...at msn.com wrote: > A new thing like tookad, for example, using light located by a chemical > which finds the place to heat up is not being marketed because it will > prolong the life of the patient. > I think it is being offered becasue it has less SEs: It is NOT being marketed, or it IS being offered? ... > I would also would like to point out that if you read the lionities sp > (not only can't be pronounced it also can't be spelled ;) piece you > should also read the erudite comments by the peers who disagree with > him for various reasons. Apercu, Have you got a specific citation that you think I should read? Thanks. Alan |
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