Proposed salvage treatment strategy for biochemical failure after radical prostatectomy in patients with prostate cancer: a retrospective study

Abstract

Background: Treatment options for patients with recurrent disease after radical prostatectomy include salvage radiotherapy of the prostatic bed and/or androgen deprivation therapy. To establish an effective treatment strategy for recurrent disease after radical prostatectomy, we retrospectively analyzed the outcome of salvage radiation monotherapy in such cases.

Methods: Data from 61 men who had undergone salvage radiation monotherapy for biochemical recurrent disease after radical prostatectomy were retrospectively reviewed. In all patients, salvage radiotherapy consisted of iraradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcome was analyzed to identify predictive factors of salvage radiotherapy.

Results: The biochemical recurrence-free survival after salvage radiation monotherapy at 2 and 5 years was 55% and 38%, respectively. Cox proportional regression models revealed that the independent predictive factors for biochemical recurrence were Gleason Score ≥ 8, negative surgical margin, and PSA velocity ≥ 0.38 ng/mL/year. Negative surgical margin and PSA velocity ≥ 0.8 ng/mL/year were significantly associated with poor response in the serum PSA levels after salvage radiotherapy.

Conclusions: Based on our findings, we propose a treatment strategy for biochemical recurrent disease after radical prostatectomy. Patients with Gleason score ≤ 7, positive surgical margin, and PSA velocity < 0.38 ng/mL/year are categorized the most favorable group, so that eradication by salvage radiation monotherapy could be expected. Other patients could be divided to two groups depending on surgical margin status and PSA velocity: 1) patients who might require combination of SRT and short-term androgen deprivation therapy and 2) patients who should be treated by androgen deprivation monotherapy.

Figure 1

Changes in serum PSA levels of patients who underwent salvage radiotherapy (SRT) for recurrent disease after radical prostatectomy. Patients were evaluated by PSA measurement at regular intervals after completing SRT. Patients who showed a decline to PSA < 0.2 ng/mL after SRT and maintained PSA < 0.2 ng/mL during the follow-up were categorized as the SRT success group (left). Patients who showed a decline to PSA < 0.2 ng/mL after SRT and thereafter experienced a rise in PSA at two consecutive measurement points with the last PSA ≥ 0.2 ng/mL (middle) were categorized as the recurrence group. If the PSA continued to rise without a decline to PSA < 0.2 ng/mL after SRT, patients were categorized as the nonresponse group (right). The recurrence group and the nonresponse group were defined as the SRT failure group.

Figure 2

Overall biochemical recurrence (BCR)-free survival. Kaplan-Meier estimates of BCR in all patients (A). Kaplan-Meier estimates of biochemical recurrence (BCR)-free survival by prostatectomy Gleason score (B), surgical margin status (C), pre-SRT PSA (D), PSA velocity (E), and PSA doubling time (F). Survival curves are compared using the log rank test. The time to biochemical recurrence is given in months.

Figure 3

Comparison of PSA-related values between the SRT success group, recurrence group and nonresponse group. Pre-SRT PSA (A), PSAV (B), and PSADT (C) were depicted by Tukey box plots. Horizontal lines within boxes indicate median levels and are depicted by horizontal lines within boxes. Significance (P < 0.05) was assessed by the Mann–Whitney U test.

Figure 4

Proposed treatment strategy for recurrent disease after radical prostatectomy. The OR that patients with three favorable factors will experience BCR after SRT monotherapy is 0.084 (95% CI 0.01-0.72). Patients showing biochemical recurrence after a decline to PSA < 0.2 ng/mL and those showing nonresponse to SRT can be distinguished by the status of the surgical margin and PSAV. The former may benefit from the combination of SRT and short course of ADT, while the latter may not receive benefit from SRT.