THE "NEW" PROSTATE CANCER INFOLINK

We have previously reported data from the 2-year follow-up of the patients participating in the PCM301 trial of vascular targeted phototherapy (VTP) — a form of prostate hemiablation — compared to active surveillance in the treatment of low-risk, localized prostate cancer. New data at 4 years of follow-up have now been published in the Journal of Urology.

There are very real questions about the appropriate timing of any form of treatment as opposed to management on active surveillance for men with low-risk prostate cancer, and we need to be clear up front that this study and this paper do not address or answer those questions. The question that this study addresses is the simpler one of what happens if you take a group of 413 patients who are candidates for active surveillance and randomize them to either active surveillance (n = 206) or immediate focal treatment with VTP (n = 207).

All patients randomized to this trial were required to have prostate biopsies at both 12 months and 24 months after randomization. After that 2-year period, patients were simply monitored over time, with periodic biopsies performed according to standards-of-care in each participating institution. The continued efficacy of cancer ablation was assessed by biopsy results overall and “in-field” (treated lobe, or lobe with index cancer). Further radical therapy was implemented based on relevant biopsy and clinical data taking account of physician and patient opinions.

The current report by Gill et al. provides follow-up data on this trial at 4 years post-randomization, and offers us the following information:

• Conversion to radical therapy was less likely in the VTP ablation cohort than the active surveillance (AS) cohort, occurring among
  • 7 percent of patients in the VTP cohort within 2 years
  • 15 percent of patients in the VTP cohort within 3 years
  • 24 percent of patients in the VTP cohort within 4 years
  • 32 percent of patients in the AS cohort within 2 years
  • 44 percent of patients in the AS cohort within 3 years
  • 53 percent of patients in the AS cohort within 4 years
• “Triggers for radical therapy were similar in the two arms.”
• “Cancer progression rates overall and by grade were significantly lower in the ablation cohort.”
• End-of-study biopsy results were negative throughout the prostate in
  • 50 percent of patients in the VTP cohort
  • 14 percent of patients in the AS cohort after surveillance
• Over the course of the study, after randomization, biopsy Gleason scores of 7 or higher were found in
  • 16 percent of patients in the VTP cohort
  • 41 percent of patients in the AS cohort
• Also, over the course of the study., after randomization, biopsy Gleason scores of 7 or higher were found in
  • 10 percent of patients in the VTP cohort within the ablated lobe
  • 34 percent of patients in the AS cohort within the originally positive lobe (that was simply monitored)

Your sitemaster has to admit that he finds interpretation of these data problematic in a number of ways, so here are some immediate observations:

• 24 percent of the men in the VTP cohort underwent radical therapy within 4 years after VTP, implying an overall progression-free survival rate for VTP of only 76 percent at 4 years.
• 10 percent of the men in the VTP cohort definitively had progressive prostate cancer within the treated lobe of the prostate within 4 years.
• The statement that “Triggers for radical therapy were similar in the two arms” of this trial seems very strange to your sitemaster, because we know that anxiety is a major driver of men coming off anxiety within the first 2 to 3 years on active surveillance, but that shouldn’t have been an issue of the same level of significance for the men who had received treatment with  VTP.
• It should be no surprise that as many as 41 percent of men in the AS cohort went on to have Gleason score of 7 or higher within 4 years on AS, but how many of those men still had only favorable, intermediate-risk disease with a small amount of Gleason 3 + 4 = 7?

The fundamental unanswered question raised in your sitemaster’s mind by this trial is this one:

• What would have happened if patients had been randomized to immediate VTP hemiablation of the prostate in Arm A, with repeat VTP hemiablation if it was possible and necessary at any time within the next 4 years, or to active surveillance in Arm B, with VTP hemiablation  as “salvage therapy” if it was possible and necessary at any time within the next 4 years, and the patients were then followed for a total of 8 years or more?

In other words, was there really any advantage to early VTP as opposed to delayed VTP in this cohort of patients? We already know that that does not appear to have been the case in patients who were randomized to surgery or radiation therapy or observation in the ProspecT trial — and those patients were less than ideal patients for active surveillance!

There are certainly patients who are unable to adapt themselves to the idea of active surveillance. VTP may be one of several possible treatments that is appropriate for such men. However, at least as far as your sitemaster is concerned, these data don’t seem to justify the idea that immediate VTP is “better” that active surveillance because we have no idea whether the patients who responded well to VTP might not have responded equally well if VTP had been used as first-line treatment at some time after initial signs of need for treatment after a period of up to 4 years on active surveillance.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: active, outcome, photodynamic, surveillance, targeted, TOOKAD, vascular, VTP |