Sunday, August 28, 2016

What should one do if one’s PSA remains detectable after radical prostatectomy?

After surgery, PSA should become undetectable on a normal PSA test within a month or two, but sometimes it remains elevated. The purpose of the ARO 96-02 randomized clinical trial was to determine whether there was an advantage to treating stage T3 patients while PSA was still undetectable, or whether they could wait to be treated. Waiting has the advantage of allowing better healing of recently cut and handled tissues, and avoiding overtreatment. In that study, there was a significant advantage to immediate treatment in preventing eventual clinical recurrence. However, the study also included 74 patients whose PSA never became undetectable, and they all received immediate radiation therapy.  Wiegel et al. did a 10-year follow-up analysis of that group to see how they fared.

Among the 74 patients:
  • ·      Their median PSA after surgery was 0.6 ng/ml (range 0.05-5.6 ng/ml)
  • ·      They were checked for distant metastases with a bone scan and X-rays.
  • ·      They all received 66 Gy of 3D CRT to the prostate fossa at a median of 86 days after surgery. 58% received adjuvant hormone therapy.
  • ·      Compared to those who reached undetectable PSA, they had higher pre-surgery PSA, stages, Gleason scores, and incidence of positive surgical margins.
  • ·      Among 48 patients for whom data was available, only 15% achieved undetectable PSA following radiotherapy
  • ·      Their 10-year clinical relapse-free survival was 63%.
  • ·      Their 10-year metastasis-free survival was 67%, compared to 83% among patients who had undetectable PSAs initially.
  • ·      Their 10-year overall survival was 68%, compared to 84% among patients who had undetectable PSAs initially.
  • ·      There were no Grade 3 or higher acute toxicities, but 7% experienced Grade 3 late urinary toxicity.

Wiegel concludes:
A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.”

This seems a reasonable conclusion. Some patients with persistent PSA after surgery will enjoy a long-term survival benefit from adjuvant radiation aimed at the prostate fossa, but a third will develop metastases and die in spite of such treatment. It seems that only 15% were actually cured, or at least became undetectable, by the therapy. It was not the purpose of their study to detect a survival benefit in this subset of patients who had persistent PSA, so there are no conclusions that can be drawn about the strategy of immediate treatment. We cannot yet reliably identify through imaging or biochemical tests those men who will benefit from immediate radiation, although some men with high or quickly rising PSA may have PET-detectable metastases.

In spite of this, Wiegel is quoted in the ASTRO press release as saying:

Our analysis demonstrates that patients who have detectable PSA post-prostatectomy may benefit from more aggressive, early and uniform treatment that could improve survival outcomes.”

This conclusion seems unwarranted from the data. It is certainly a reasonable decision, and one that many patients will make in consultation with their radiation oncologists.

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