As a follow-up to yesterday’s report on Scardino’s presentation to the New York section of the AUA, it is worth noting a publication last November from Johns Hopkins. The research group’s goal was to investigate long-term survival following radical prostatectomy as first-line treatment in their patients with high-risk prostate cancer.
According to Loeb et al., between 1992 and 2008, a single surgeon (presumably Patrick Walsh) treated 175 men with D’Amico high-risk prostate cancer (clinical stage ≥ T2c, biopsy Gleason score 8-10, or PSA > 20 ng/ml) with radical prostatectomy at Johns Hopkins. A careful analysis of data from these patients showed the following:
- 63/175 patients (36 percent) had organ-confined disease.
- At 10 years, for this subset of 63 patients only,
- Biochemical recurrence-free survival was 68 percent.
- Metastasis-free survival was 84 percent.
- Prostate cancer-specific survival was 92 percent.
- The rate of freedom from any hormonal therapy was 71 percent.
- Of the high-risk criteria, a biopsy Gleason score of 8-10 (as compared to a Gleason score of ≤ 7) was the strongest independent predictor of biochemical recurrence, metastases, and prostate cancer death.
The authors also note that, despite considerable stage migration associated with widespread PSA screening, during the time frame covered by this study, up to a third of incident prostate cancers have had high-risk features. It has been customary to treat many of these patients with combined radiation and androgen deprivation therapy. They state that it is possible that RP is underutilized for the management of high-risk, clinically localized prostate cancer.
Loeb et al. conclude that the Hopkins data “suggest that surgical treatment can result in long-term progression-free survival in a subset of carefully selected high-risk men.”
It would have been helpful if the Hopkins group had provided 10-year follow-up data for all 175 of these patients, and not just the ones with apparently organ-confined disease at the time of surgery. This would have allowed a more direct comparison of the Hopkins data to the Memorial Sloan-Kettering data presented by Scardino. However, we will have to do the best we can with what is available! In a previous paper based on the Johns Hopkins series of patients, Trock et al. had already shown that, “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.” This paper was cited by Scardino in his presentation as confirming his opinion that second-line radiotherapy was an important option for treatment of men with high-risk prostate cancer after initial treatment with surgery.
Filed under: Diagnosis, Management, Risk, Treatment Tagged: | "high risk", outcomes, radical prostatectomy, surgery
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Hmm … one third of the patients supposedly had organ-confined disease and of these one third had residual PSA after surgery. Is this considered good after 10 years of followup? What would the resullts be at 15 years? More importantly, what happened with the 66% of the patients in this study? Hopkins obssesion not to treat early recurrence after surgery (a la Messing) is notable and misguided. Still, Walsh’s results support debulking to improve survival for these 1/3 of the patients.
Why are we so surprised at Scardino’s results? Zincke at Mayo has promoted debulking of advanced disease for decades. The Holmberg et al. study clearly showed that radical surgery changes the natural course of the disease by promoting overall and disease-specific survival. Guess that the negative misinformation campaign is still in great shape…and what else is new?
The fact that many (better term would be some) men are treated unnecessarily needs a better definition in Dr. Scardino’s presentation. Age is a factor that needs to be considered in the to treat or not to treat decision. Biopsy Gleason score correlation with surgical pathology results are improving but there is still a degree of uncertainty that makes the final decision very difficult.
Once again, Ralph, I don’t expect you to be surprised at the results Scardino presents. What is “surprising” (IMHO) is that Scardino is effectively saying that surgeons ought to focus the use of their skills more on men with higher-risk disease and less on men with low-risk disease because a radical prostatectomy is a procedure designed to excise cancer as its first priority, and it comes with serious side effects (even in the very best hands).
What is JHU’s side of this story? Surely they are not trying to do patients harm. So what is their reasoning for deferring further treatment (presumably, in most cases, radiation, but maybe in some cases ADT) upon evidence of recurrence? What are the JHU guidelines for initiating further treatment, post surgery? How do those guidelines differ from the practices at MSKCC?
All that I can tell you is that for many, many years, Dr. Walsh and his colleagues at Johns Hopkins argued that there was no benefit associated with the early use of hormone therapy (until there were clear signs and symptoms of metastatic disease) and that the early use of radiation therapy in men with a rising PSA post-prostatectomy was also of dubious value.
The question of whether early hormone therapy actually provides a real survival benefit is still unresolved (although there are data suggesting that it may). There are now clear data, however, that the early and long-term use of hormone therapy has real and serious adverse events (including the risk of death).
There are also clear data (including data from Johns Hopkins, referenced above) that early radiation therapy certainly does improve the survival of men with a rising PSA post-surgery.
Exactly how the prostate cancer experts at Johns Hopkins have revised their protocols in order to optimize outcomes for their current patients based on this information would have to be addressed to Johns Hopkins.
Mike,
Sure RP has side effects. How about the side effects of progression and death from PCa? Are we to ignore those? Age is a significant factor in treatment/no treatment decisions.
If the Holmberg study and the Messing study results are ignored, then it is certain that hormone treatment has not been proven to improve survival (both overall and disease-specific). It is a fact that salvage treatments do cause side effects but their survival benefits should be be provided to patients so that their decisions are personal and not dictated by others.
I forgot to mention that Walsh very conveniently supports the value of surgery demonstrated by the Holmberg study while ignoring the fact that HT was offered to both arms of the study when recurrence occurred. How is that for creative thinking and ignoring results by Hopkins?