Long-term outcomes of radiotherapy and impact of nodal disease burden in clinically node-positive prostate cancer

Abstract

Purpose

The optimal management for pelvic clinical node-positive (cN1) prostate cancer remains controversial and randomized evidence for local therapy is lacking. Recent data suggest that common-iliac nodal metastases might carry a prognosis similar to that of cN1 disease when treated radically. In this context, we retrospectively reviewed the experience at our centre of treating cN1 prostate cancer, with or without common-iliac nodal metastases, focusing on the role of radiotherapy and the effect of nodal disease burden on survival.

Materials and methods

The study population consisted of men diagnosed with prostate cancer between 2002 and 2018 with cN1 disease and/or common-iliac nodal metastases and treated with androgen deprivation therapy and/or definitive local therapy. Outcomes of interest included overall survival and castration resistance-free survival, which were estimated using the Kaplan-Meier method. Univariable and multivariable Cox regression were used to identify factors associated with overall – and castration resistance-free survival. In the subgroup of patients treated with radiation, the association between a number of variables – including biologically effective dose to the prostate, use of elective pelvic nodal radiotherapy, and escalated dose (radiotherapy boost) to positive nodes–and overall survival was studied.

Results

A total of 87 patients were included, of whom 14 had common-iliac nodal metastases and 68 received radiotherapy. Median follow-up was 110 months. On univariate analysis, radiotherapy was associated with improved overall survival (hazard ratio [HR]: 0.28, 95 % confidence interval [CI]: 0.14–0.55, P < 0.0005) and castration resistance-free survival (HR: 0.22, 95 % CI: 0.12–0.41, P < 0.0005). Median overall survival in those patients receiving radiotherapy was 134.9 versus 63.1 months in those not receiving radiotherapy. Receipt of radiotherapy remained significantly associated with overall survival on multivariable analysis (HR: 0.13, 95 % CI: 0.05–0.32, P < 0.001). Biopsy Gleason score 10 and presence of more than two positive lymph nodes were associated with worse overall survival while presence of common-iliac nodal metastases was not found to have any significant association with overall survival. In patients treated with radiation, increasing the biologically effective dose to the prostate was associated with improved overall survival (HR: 0.73 per 10 Gy, 95 % CI: 0.54–0.97, P = 0.03) while use of elective pelvic nodal radiotherapy and use of a radiotherapy boost to positive nodes had no significant association with overall survival.

Conclusion

In this cohort, we evaluate the impact of radiotherapy in pelvic clinical node-positive prostate cancer that includes common-iliac nodal metastases. Receipt of radiotherapy was associated with improved oncologic outcomes. The number of positive pelvic nodes, but not their common-iliac location, was prognostic.