Prostate Cancer–Specific Survival Following Salvage Radiotherapy vs Observation in Men With Biochemical Recurrence After Radical Prostatectomy

Abstract

Context Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy, but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival, and if so, the subgroup of men most likely to benefit. Objectives To quantify the relative improvement in prostate cancer-specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy, and to identify subgroups for whom salvage treatment is most beneficial. Design, Setting, and Patients Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982-2004, followed up through December 28, 2007, who experienced biochemical and/or local recurrence and received no salvage treatment (n = 397), salvage radiotherapy alone (n = 160), or salvage radiotherapy combined with hormonal therapy (n=78). Main Outcome Measure Prostate cancer-specific survival defined from time of recurrence until death from disease. 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]; PϽ.001). 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). 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. Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer-specific survival. Men whose prostatespecific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer-specific survival. Salvage radiotherapy also was associated with a significant increase in overall survival. 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.

Disease-specific outcomes of Radical Prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time

“…Our observation of post-prostatectomy PSA-DT as the strongest predictor of CF and PCD in patients with BF is consistent with numerous other studies recognizing the importance of PSA-DT as a predictor of CF [ 21 , 22 , 38 ] and PCD [ 37 , 39 , 40 ] after RP. We found the same pattern in both health regions, thereby internally validating these results.…”

Long-Term Follow-Up and Risk of Cancer Death After Radiation for Post-Prostatectomy Rising Prostate-Specific Antigen

“…We found Gleason score (8 to 9) and PSA (>1.0 ng/ ml) at the start of XRT to be major risk factors for death from prostate cancer, consistent with the findings of others (23). There was a strong trend towards risk of death based on pathology findings (SV+).…”

“…This is a consistent finding across studies (18,19,22,21,23), and a PSA level failure rate of 82% at 5 years in these patients has been reported (21). Another finding consistent for prognosis is the preradiation PSA level (18,19,22,21,23). The studies were not designed to determine the absolute lowest level at which radiation should start, but significantly worse prognosis was found for patients with a PSA level of >2.0 ng/ml (19), 1.0 ng/ml (21), and 1.3 ng/ml (18).…”

“…In our study, a Gleason score of >8 indicated a poor prognosis, with 83% of patients failing by 5 years. This is a consistent finding across studies (18,19,22,21,23), and a PSA level failure rate of 82% at 5 years in these patients has been reported (21). Another finding consistent for prognosis is the preradiation PSA level (18,19,22,21,23).…”

PSMA PET/CT findings in high‐risk biochemical recurrence after local treatment of prostate cancer

“…While patients that underwent RP or RT had similar rates of PSMA PET/CT positive lesions, patients that underwent both RP plus RT had lower rates of subsequent PSMA PET/CT positive lesions, suggesting a potential benefit to adjuvant or early salvage therapy, which is consistent with other studies 21,22 . In combination, RP plus RT may work to decrease any micro‐metastatic disease that is present at the time of initial treatment.…”