There were a number of significant prostate cancer presentations today, and while none of them were “game changing” (for a variety of reasons), they are certainly worthy of notice.
In the first place, data from two studies presented at an oral abstract session this morning confirmed the potential of radiation therapy in combination with hormone therapy for men diagnosed with high risk prostate cancer (clinical stage T3/4 and at least one other high-risk factor).
Warde et al. presented the results of a large, randomized, multi-center, Phase III clinical trial designed to compare treatment of high-risk patients with long-term androgen deprivation therapy (ADT) to treatment of similar patients with external beam radiation therapy (EBRT) + ADT. This trial was first initiated in 1993, and the results presented today represent data from an interim analysis carried out in late 2009. Futher data from this trial are still to come. However, this trial basically showed that high-risk patients treated with EBRT and ADT had significantly better overall and prostate cancer-specific survival than men treated with ADT alone. Specifically:
- Median patient follow-up is 6.0 years.
- 320 patients have died — 175 on ADT alone and 145 on ADT+EBRT.
- Addition of EBRT to ADT significantly reduced the risk of death (hazard ratio [HR] = 0.77).
- 140 patients died of prostate cancer and/or treatment for prostate cancer — 89 on ADT alone and 51 on ADT + EBRT.
- Addition of EBRT to ADT significantly reduced the risk of prostate cancer-specific mortality (HR = 0.57).
In the second trial, Mottet et al. also reported on the impact of EBRT when combined with ADT compared to ADT alone in a randomized, multi-center, Phase III trial. However, this was a smaller trial in which progression-free survival was monitored for just 5 years. This trial concluded that, in patients with locally advanced prostate cancer, the addition of local EBRT to ADT with 3 years of treatment with an LHRH agonist significantly reduced the risk of clinical progression.
It is important, in appreciating the significance of these studies, to recognize that exactly which patients with locally advanced, high-risk disease are most appropriate for EBRT, EBRT + ADT, or even ADT alone is still unknown. We also do not have definitive data on how long the EBRT should be given. Nor do we know whether EBRT combined with intermittent ADT would be appropriate for those patients who are good candidates for the combination therapy. In providing commentary on the two papers above-mentioned, D’Amico reviewed these issues in detail and discussed the structure of potential future trials that might be able to help to resolve some of these issues.
Other data presented today included papers giving updates on the following:
- The results of the Phase III clinical trial showing that the new taxane called cabazitaxel is effective in extending the overall survival of patients with castration-resistant prostate cancer (CRPC) who have relapsed after docetaxel-based chemotherapy. (We had previously reported on the results of this trial from the Genitourinary Cancers meeting last March.)
- The results of the Phase III trial comparing docetaxel + prednisone with and without bevacizumab in the treatment of men with metastatic CRPC. We had previously reported that the addition of bevacizumab did not help to extend overall survival of these patients. The detailed results show that the addition of bevacizumab did extend progression-free survival but was associated with an increase in morbidity and mortality compared to the standard therapy of docetaxel + prednisone.
One final paper we would mention from today’s presentations was a paper by Trock et al. on the surgical outcomes (and the implications for curative therapy) in men undergoing delayed radical prostatectomy after participation in the Johns Hopkins active surveillance protocol.
The analysis of the available data was complex, and cannot be considered categorical, but Trock argued that the Hopkins data suggests that only that small number of patients on the Hopkins active surveillance protocol who had a later biopsy showing upgrading of their Gleason score from 6 or less to 7 or more because their earlier biopsies had missed the higher-grade cancer were at any worse risk of a poor outcome after active surveillance than similar men who had an immediate radical prostatectomy.
It is still hard to know exactly how to interpret data like this from the few long-term active surveillance protocols. Suffice it to say that in commenting on this paper, Dr. D’Amico was not entirely convinced about the conclusion — and nor are we. However, what is still clear is that men considering active surveillance as a means of managing low- and even very low-risk prostate cancer must recognize that there is a risk for pathological upgrading at subsequent biopsy which could be associated with risk for a potentially non-curable tumor. This also suggests that (as yet) we have taken insufficient account of potentially competitive risks for mortality from other causes in attempting to determine who is a good candidate from active surveillance.