Role and Optimal Duration of Hormonal Treatment in Association With Salvage Radiation Therapy After Radical Prostatectomy

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TAKE-HOME MESSAGE

•This study assessed data from 1264 patients undergoing salvage radiation therapy (RT) after radical prostatectomy (RP) at eight referral centers to understand the role and optimal duration of androgen-deprivation therapy (ADT) in this setting. The main endpoint was clinical recurrence as defined by imaging. Overall, 13% of men developed clinical recurrence at a median 8-year follow-up. Duration of ADT was statistically significant for patients with two or more risk factors (Gleason 8 or higher, pT3B or greater, PSA 0.5 or higher at RT). In this group, ADT was beneficial when given for up to 36 months. In patients with one risk factor, concomitant ADT was beneficial when administered for a shorter time (<12 months). In patients with no risk factors, the risk of recurrence remained low and constant regardless of ADT duration.

•These data suggest that patients with more adverse features benefit from long-term concomitant ADT in a salvage setting following RP, whereas patients without any risk factors may not benefit from ADT.

– Gautam Jayram, MD

abstract

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BACKGROUND

The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial.

OBJECTIVE

To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics.

DESIGN, SETTING, AND PARTICIPANTS

The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2).

RESULTS AND LIMITATIONS

Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration.

CONCLUSIONS

The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.

PATIENT SUMMARY

We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.

European Association of Urology

Assessing the Role and Optimal Duration of Hormonal Treatment in Association With Salvage Radiation Therapy After Radical Prostatectomy: Results From a Multi-Institutional Study

Eur Urol 2019 Feb 21;[EPub Ahead of Print], N Fossati, D Robesti, RJ Karnes, M Soligo, SA Boorjian, A Bossi, G Coraggio, N Di Muzio, C Cozzarini, B Noris Chiorda, G Gandaglia, S Scarcella, D Bartkowiak, D Böhmer, S Shariat, G Goldner, A Battaglia, S Joniau, K Haustermans, G De Meerleer, V Fonteyne, P Ost, H Van Poppel, F Montorsi, T Wiegel, A Briganti

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Yet some RO's, MO's point to the SPPORT trial prelim results along with evidence that ADT boosts radiation effectiveness, as rationale for short-term inclusion.