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Cancer: Prostate Message Board

Cancer: Prostate Board Index

[QUOTE=flyfisher37;3947008]Hi Jim,

Always nice to hear from you.

[COLOR="DarkGreen"]Hi Lionel,

It's always nice to hear from you too and to learn how you are doing and what you are thinking about. Thanks for pointing out this recent study. It's very encouraging, but I actually am convinced patients will do even better than suggested in this study and am giving some of the reasons below, inserted in the abstract that you quoted. Based on your tip I just took a look at the abstract myself on [url][/url], and I'm going to give the abstract the color orange and put my comments in green. Jim[/COLOR]

I was reading about a study that was published in the JAMA and had to do with salvage radiation. One of the doctors in the study was Alan Partin. Is he the one that originated the Partin tables?

[COLOR="DarkGreen"]Yes, he's the one, and quite a surgeon himself. You may also notice that Dr. Patrick Walsh is the senior (last) author in this Johns Hopkins research.[/COLOR]

You might find this interesting as would anyone who has had or is undergoing salvage radiation for recurrence after radical prostatectomy. Of course this is not the entire article.

[COLOR="darkgreen"][COLOR="DarkOrange"]"Results With a median follow-up of 6 years after recurrence and 9 years after prostatectomy, 116 men (18%) died from prostate cancer, including 89 (22%) who received no salvage treatment, 18 (11%) who received salvage radiotherapy alone, and 9 (12%) who received salvage radiotherapy and hormonal therapy. Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer–specific survival relative to those who received no salvage treatment (hazard ratio [HR], 0.32 [95% confidence interval {CI}, 0.19-0.54]; P<.001).

[COLOR="DarkGreen"]That's striking! Really impressive! :D I'm not sure why they are calling it a 3-fold improvement rather than a 2-fold improvement (22% vs. 11%), but there is probably a good reason. That "P<.001" is also impressive, meaning there is an extremely small likelihood that the result is due to chance rather than to a real difference in treatment results. It means the study group was large enough to lend huge confidence to the results, with the true outcome falling somewhere between 19% and 54% death for the salvage group compared to 100% for the no-salvage group. (That may be confusing to those unfamiliar with statistics; if the study were immensely large, say 1,000 patients for this kind of study, that range of 19% to 54% would get much smaller - zeroing in on the true value.)[/COLOR]

Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer–specific survival (HR, 0.34 [95% CI, 0.17-0.69]; P = .003).

[COLOR="darkgreen"]This is where patients and many doctors may be mislead if they do not understand the context. To me, it suggests that hormonal therapy actually, in all likelihood, made quite a worthwhile contribution :D, even though at first glance it looks like patients had a higher death rate of 12% if they added radiation to hormonal therapy instead of the 11% death rate with radiation alone. There are at least several reasons.

First, it is almost a certainty that patients getting the combination of radiation and hormonal therapy had much more serious cases and evidence of much more challenging recurrences, such as a shorter PSA doubling time, perhaps bone scans showing metastases, etc. The complete paper for the study probably provides enough information to see if that was the case, but you cannot tell from just the abstract. Maybe someone on the board could somehow access the paper and report back. In part I believe that because in the years when many of the patients were treated (spanning 1982 - a long time ago, to 2004), hormonal therapy was often reserved until patients had symptoms of advanced disease.

Second, reserving hormonal therapy was especially common at Johns Hopkins. In other words, it is likely that patients did not get a hormonal boost to the radiation until they had clear evidence of metaststic disease. Unfortunately, while hormonal therapy helps quite a bit with metastatic disease, it appears to be much more effective when used earlier.

Third, the hormonal therapy available in the 80s and 90s was no where near as effective, we are highly confident, as the versions of hormonal therapy now available. For instance, there is increasingly convincing evidence that single-drug hormonal therapy - most typically with Lupron or Zoladex injections - is substantially less effective than combined therapy involving an antiandrogen drug (typically these days Casodex, but also flutamide and others). Additionally, adding finasteride (generic version of Proscar) or Avodart as the third class of drug appears to help a lot. Also, in the early years of the study, probably into this decade, the importance of supportive bisphosphonate therapy (Fosamax, Boniva, Zometa, etc., with calcium and vitamin D supplementation) was not appreciated. That therapy not only goes a long way toward preventing or minimizing bone loss as a side effect of hormonal therapy, but it also helps prevent, stabilize or reverse bone metastases from prostate cancer, especially if Zometa is used. Certain cardiovascular risks can also increase due to hormonal therapy, and we now have statins and other drugs that can minimize or eliminate those risks. At the times most patients were under treatment in the study, it is likely that the cardiovascular risks of hormonal therapy were not understood, so countermeasures, even if available, would have been less likely to have been employed.

Finally, all this means that, even with almost surely inferior hormonal treatment, results were achieved (12% death, 88% survival) that were nearly equal to those of patients with almost surely much less serious cases who got just radiation (11% death, 89% survival). :D (I hope that the researchers brought out some of these subtle but vital points in the discussion section of the paper.)

Does that make sense to? It looks clear to me. However, I expect we will see presentations and hear doctors quote the simple version that hormonal therapy did not help. That to me would be a sign that the doctor is outside of the range of his expertise and is quoting the conventional, not-so-smart wisdom. :(


The increase in prostate cancer–specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors.

[COLOR="darkgreen"]In other words, the superior outcomes in this study - where salvage radiation made a difference - were among those men with more aggressive cancer recurrences. I suspect this means that for those with less aggressive recurrences, adding radiation was not necessary for most - they would do pretty well on their own. Some of the same researchers as on this team have been involved in the Freedland study that has been such a huge help in separating serious recurrences from mild ones, many of the latter requiring no follow-up therapy. [/COLOR]

Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer–specific survival.

[COLOR="darkgreen"]In other words, delaying salvage radiation for more than two years eliminated a benefit. We now know that it is wise to have salvage radiation fairly early, probably shortly after the patient has recovered from the surgery and a recurrence is clear would be best, but hopefully before the PSA reached 1.0. That know-how (or "know-when" here) may have not been available when many of the patients in this study were treated. [/COLOR]

Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer–specific survival.

[COLOR="darkgreen"]These would be men with more serious prostate cancer. Considering that many would have been treated in the 80s and 90s, it's likely that PSA tests used to monitor recurrence were only sensitive down to .2 or .1, a far cry from today's ultrasensitive tests that are reliably a hundred times more sensitive. That means that these men were only able to achieve a lowest PSA after surgery that we consider rather high and unfortunate by today's standards. I think it's likely that many would have had cancer that had spread beyond the prostate, probably well beyond the prostate - distant spread, at the time of surgery. This would be tougher for radiation to cure.

Also, radiation technology available then was much less effective than the technology we have today. For one thing, we now know that higher dosing levels are needed, and, in contrast to the past, they can be delivered fairly safely, avoiding substantial long-term side effects.[/COLOR]

Salvage radiotherapy also was associated with a significant increase in overall survival.

[COLOR="darkgreen"]That's always very important to know. It's not enough to just cure the cancer; it's important that the treatment does not reduce overall survival due to its complications and side effects.[/COLOR]

Conclusions Salvage radiotherapy administered within 2 years of biochemical recurrence was associated with a significant increase in prostate cancer–specific survival among men with a prostate-specific antigen doubling time of less than 6 months, independent of other prognostic features such as pathological stage or Gleason score. These preliminary findings should be validated in other settings, and ultimately, in a randomized controlled trial. "[/COLOR][/COLOR]
Maybe there is some hope after all?

[COLOR="darkgreen"]Definitely! This study certainly supports optimism, but the hope is not based just on this study. Several other threads also apply: "If lymph nodes are positive after RP; hormonal therapy as a sound tactic" (started 2/4/2008; and "Gleason 8 (and higher) cancer: not good, but not always the end of the world," started 2/6/2008. :angel: :D :cool:[/COLOR]

Take care....Lionel[/QUOTE]

How does this look to you?

Take care and hang in there,

Jim :wave: :cool:

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