Clinical Outcome of Salvage Radiotherapy for Locoregional Clinical Recurrence After Radical Prostatectomy

Abstract

Objectives: To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Methods: Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Results: Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, P = .031) and OS (HR 17.72, 95% CI 1.75-179.64, P = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, P = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. Conclusions: SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.

Dose-Escalated Salvage Radiotherapy for Macroscopic Local Recurrence of Prostate Cancer in the Prostate-Specific Membrane Antigen Positron Emission Tomography Era

“…This is in line with the published data on salvage radiotherapy for macroscopic local prostate cancer recurrence, as Bruni et al, Zilli et al, and Zaine et al did not observe a benefit in biochemical control from higher doses [12][13][14]. For dose-escalation, most published studies utilized a sequential boost or a SIB at two dose levels [10,[12][13][14][15]. The radiotherapy concept for macroscopic local recurrence at our institution included a SIB at up to three dose levels: PTV Boost1 encompassed the prostate bed and spared the rectum, while the highest dose, PTV Boost2 , encompassed the macroscopic local recurrence without an additional margin.…”

“…We escalated the radiation dose to the local recurrence up to a median total dose of 69.3 Gy, which is comparable to the studies of Zaine et al and Lee et al [13,15]. In primary prostate cancer, the FLAME trial demonstrated better biochemical control by doseescalating the GTV up to 95 Gy [31].…”

“…Pre-SRT PSA value might be a surrogate marker for disease spread, and thorough staging with modern imaging naturally seems as though it would be important for discriminating local from advanced disease. Several studies on salvage radiotherapy for macroscopic prostate cancer recurrence did not employ, or only partly employed, PSMA PET/CT as pre-SRT staging [10][11][12][13][14][15][16][17]. Therefore, potential understaging in the mentioned trials may explain the difference in biochemical control compared with our study.…”

“…Zilli et al, for example, reported 7.3% grade 3-4 GU late toxicity and 1.8% late grade 3 GI toxicity with 64 Gy plus a 10 Gy boost, which represents the higher end of the spectrum [33]. Most other studies reported between zero and two cases of late grade 3 toxicity [10,12,13,15].…”

“…Despite being an important clinical scenario, no consensus for dose-escalated radiotherapy for macroscopic recurrence in the prostate bed exists [11]. Moreover, as most retrospective studies for macroscopic prostate cancer recurrence have used conventional imaging or predominantly choline PET/CT imaging as a pre-SRT staging method, data from PSMA PET/CT-based SRT for macroscopic relapse are still limited at present [10][11][12][13][14][15][16][17].…”