Introduction

Recent prospective randomized studies showed that concomitant use of hormonal therapy (HT) increased outcomes after salvage radiation therapy (SRT). However, these studies were limited by the inclusion of a significant proportion of patients treated in a late salvage setting. We hypothesized that the beneficial effect of concomitant use of HT decreases when patients are treated with early SRT.

Methods

The study included 706 patients who received SRT at six tertiary referral centres for PSA rising after RP. The irradiation of the pelvic lymph nodes area was left at the discretion of the treating physician. The study outcome consisted of distant metastasis developed after SRT, including retroperitoneal nodal metastasis (M1a), skeletal (M1b), and visceral metastasis (M1c). Multivariable Cox regression analysis was used to test the association between the study outcome and the following predictors: patient age, pT stage (≤pT3a vs. ≥pT3b), pathologic Gleason (≤7 vs. ≥8), surgical margins (negative vs. positive), PSA level at SRT, and concomitant hormonal therapy (HT) administration. Non-parametric curve fitting method was used to plot the risk of distant metastasis over PSA level at SRT. Results were stratified according to the use of HT (no vs. yes).

Results

Median age and PSA level at SRT were 66 years and 0.40 ng/ml. Overall, 214 (30%) patients received concomitant HT. At a median follow-up of 84 months, 15 (2.1%), 54 (7.7%), and 9 (1.3%) patients developed retroperitoneal, skeletal, and visceral metastasis, respectively. At multivariable analysis, PSA level at SRT (HR: 1.19, p=0.004) was a significant predictor of distant metastasis. The association between distant metastasis and PSA level at SRT significantly differed by concomitant HT (p<0.0001 by an interaction test). Specifically, the benefit of HT was minimal for PSA level <1 ng/ml, and it increased exponentially for PSA level >2 ng/ml (Figure 1).

Conclusions

The oncological benefit of concomitant HT greatly depends on PSA level at SRT. Our retrospective data suggest a clear benefit of adding HT to SRT only in patients with PSA >2 ng/ml, whereas hormonal therapy had minimal effect on progression in men receiving SRT at a PSA <1 ng/ml at SRT.

Funding

none