Date Published: April 11, 2019
Publisher: Public Library of Science
Author(s): Changhoon Song, Sang Jun Byun, Young Seok Kim, Hanjong Ahn, Seok-Soo Byun, Choung-Soo Kim, Sang Eun Lee, Jae-Sung Kim, Christopher J.D. Wallis.
To investigate whether whole pelvic radiotherapy (WPRT) improves biochemical relapse-free survival (bRFS) vs. prostate bed radiotherapy (PBRT) in prostate cancer patients receiving salvage radiotherapy (SRT) after radical prostatectomy.
Data from patients with prostate cancer who underwent SRT for biochemical recurrence between 2005 and 2012 in two academic institutions were retrospectively reviewed. Patients treated with WPRT in one hospital were compared with patients treated with PBRT in the other. Propensity scoring was performed to balance the characteristics of the different treatment groups, and bRFS was compared.
Data from a total of 191 patients were included in the analysis (WPRT, n = 108; PBRT, n = 83). The median follow-up period was 66 months. Prior to matching, patients who received WPRT had higher pathologic Gleason scores as well as a higher incidence of pre-SRT PSA levels >0.5 ng/mL and lower rates of concurrent androgen-deprivation therapy. Propensity score matching balanced these characteristics and generated a cohort comprising 56 patients from each group. In the matched cohort, the 5 year bRFS of the WPRT group was significantly higher than that of the PBRT group (65.9 vs. 42.2%, p = 0.017). Multivariate analysis revealed that WPRT was an independent prognostic factor for bRFS (hazard ratio: 0.45, 95% confidence interval: 0.26–0.75, p = 0.002). This benefit of WPRT on bRFS was maintained in subgroup analyses, especially in patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL.
These data suggest that, following radical prostatectomy, elective WPRT during SRT may improve bRFS compared with PBRT in selected patients. Patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL represent a potential subgroup who benefit most from receiving WPRT. Results of prospective randomized trials are awaited to confirm this finding.
Salvage radiotherapy (SRT) of the prostate bed in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for the treatment of prostate cancer is associated with higher rates of biochemical control as well as lower rates of distant metastases, cancer-specific mortality, and all-cause mortality in some patients [1–3]. Consequently, its use has been included in guidelines developed by the American Urological Association in collaboration with the American Society for Radiation Oncology . However, more than half of all patients treated with SRT will experience disease progression [1, 5, 6] and more intensive treatment approaches are required to improve outcomes in these patients.
Data were reviewed from 345 consecutive patients with surgically staged prostate cancer treated with postoperative radiotherapy (RT) after RP between 2005 and 2012 at the Seoul National University Bundang Hospital or Asan Medical Center. None of the patients showed any clinical evidence of distant metastases before they received SRT. Current study was conducted in accordance with the standards and regulations of Korean Good Clinical Practice. Investigators are authorized to proceed the study with approvals of the institutional review board of Seoul National University Bundang Hospital and Asan Medical Center. The requirement for informed consent to participate the study was waived due to its retrospective design.
Data from 191 patients were included in the analysis (PBRT, n = 83; WPRT, n = 108). The median follow-up period was 66 months with an interquartile range (IQR) of 53–89 months. The median age at RP and SRT was 66 and 67 years, respectively; the median total prostate bed dose was 66.0 Gy, and median pre-SRT PSA level was 0.550 ng/mL. Intensity modulated radiotherapy and three-dimensional conformal radiotherapy were used in 71% and 29% of patients, respectively. WPRT was offered to 44% of patients with a pGS of 7 and 72% with a pGS of 8–10. ADT was administered concurrently with SRT in 103 (54%) patients (56% pGS 7, 51% pGS 8–10). Median duration of ADT was 17.0 months (IQR 9.7–24.0 months). Median number of nodes dissected was five (IQR 3–7). Details of descriptive statistics relating to patient, tumor, and treatment characteristics for the entire cohort (n = 191), as well as the propensity score-matched cohort (n = 112), are summarized in Table 1. In the entire cohort, there were significant imbalances in these characteristics between the two groups. Briefly, patients who underwent WPRT had higher pGS as well as higher rates of pre-SRT PSA levels >0.5 ng/mL, and lower rates of concurrent ADT. Propensity score matching resulted in a cohort of 56 patients in each group. In the matched cohorts, there were no between-group differences with respect to patient, tumor, and treatment characteristics.
Approximately 30% of patients treated with RP for prostate cancer experience disease recurrence, often first evidenced by rising PSA levels [17, 18]. SRT reduces the incidence of distant metastases, cancer-specific mortality, and all-cause mortality compared with observation only [1–3]. However, the optimal radiation target volume, which is based on individualized risk, has not been established in this setting, and RT to the prostatic bed only is recommended by several consensus guidelines [19, 20]. Limitations to establishing the anatomic location of the occult disease with current imaging modalities also hinder the selection of an appropriate target volume. A recent study reports patterns of recurrence after PBRT, as identified by C-11 choline positron emission tomography . In this study, the majority of recurrences were located outside the prostate fossa and in the pelvic nodal area, particularly inferior to the aortic bifurcation. Although these findings should be interpreted with caution, being hypothesis-generating at best, they did suggest a possible need for nodal irradiation. For selected, high-risk patients, WPRT is often used to irradiate pelvic lymph nodes, which may harbor occult metastases [11, 22]. This study furthers understanding of the clinical implications of BCR after RP and the treatment effect of WPRT during SRT, confirming the results of previous studies demonstrating that WPRT (with or without ADT) can reduce the incidence of subsequent secondary biochemical relapse [11, 13]. With regard to the potential increase in toxicity following WPRT compared with PBRT in the postprostatectomy RT setting, several studies have demonstrated that the risk of developing late GI toxicity is significantly reduced with intensity modulated radiotherapy compared with three-dimensional conformal radiotherapy [15, 23, 24].
Elective WPRT during SRT may improve bRFS compared with PBRT in selected patients. Patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL represent a potential subgroup who benefit most from receiving WPRT. Results of prospective randomized trials are awaited to confirm the benefit of elective WPRT during SRT.