ADT’s benefit studied in post-RP men undergoing salvage RT

“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature. Dr. Mian is professor of surgery in the division of urology at Albany Medical College, Albany, NY.

Biochemical recurrence after radical prostatectomy (RP) may occur in 20% to 50% of cases and salvage radiation therapy (SRT) is considered the best treatment in most cases. But the questions about whether to add androgen deprivation therapy (ADT), as well as its dose and duration, remain subjects of active clinical debate.

Two previously published studies have demonstrated either improved overall survival or progression-free survival in men treated with a combination of SRT with ADT. At the same time, there is increasing awareness about significant adverse effects associated with the use of ADT, which can result in worse quality of life. The rate and severity of these side effects depend on the ADT duration.

In a recent report by Fossati et al, the authors aimed to study the impact of SRT plus ADT on clinical recurrence in relation to the duration of ADT and tumor characteristics (Eur Urol Feb. 21, 2019 [Epub ahead of print]).

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The study included 1,264 patients from eight tertiary referral centers, between 1996 and 2012, who received SRT to the prostatic and seminal vesicle bed, with or without concomitant ADT. These patients had pathologic stage T2-4, N0-Nx, M0-Mx. Most of the patients (1,125, 89%) received SRT for rising PSA, while others were treated due to persistent PSA (139, 11%) after surgery.

The median dose of SRT was 66 Gy (interquartile range, 63-66 Gy). Whole-pelvis SRT was administered to 430 patients (24%). The decision to irradiate the pelvic lymph nodes and the type, dose, and duration were left to the discretion of treating physicians.Three risk factors identified

After a median follow-up of 93 months, 182 patients developed clinical recurrence (CR), defined as local recurrence, pelvic or retroperitoneal lymph node recurrence, or visceral or skeletal metastases noted on radiologic studies. The estimated CR-free survival rate at 8-year follow-up was 92%. Multivariable analysis revealed that concomitant ADT duration was inversely associated with the risk of CR (hazard ratio per 2 mo: 0.95, 95% CI: 0.92-0.99; p=.022). Further, pathologic stage ≥pT3b (HR: 3.79; p<.0001), pathologic Gleason score ≥8 (HR: 1.99; p<.0005), and PSA level ≥0.5 at RT (HR: 1.18; p=.015) were associated with increased risk of CR after SRT±ADT.

Of these three risk factors, 531 patients (42%) had zero, 507 (40%) had one, and 226 (18%) had two or more risk factors. The estimated 8-year Kaplan-Meyer CR-free survival rate was 94%, 89%, and 71% for men with zero, one, and two or more risk factors, respectively (p<.0001).

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In men with two or more risk factors, increasing duration of concomitant ADT (up to 36 months) was beneficial in reducing the risk of CR by nearly one-half in the first 12 months and an additional 25% by 18 months of ADT. In men with only one risk factor, there was some benefit noted when ADT was used for ≤12 months but not with longer duration of ADT. Finally, in men without any of these three risk factors, the risk of CR was low and did not improve with concomitant ADT.

Interestingly, surgical margin status, which has demonstrated variable prognostic value, was not used as one of the main risk factors. This multicenter retrospective study is not able to provide guidance regarding the best dose of SRT or the type of hormonal suppression associated with the lowest risk of CR. The authors also do not report on the location of CR in men with variable risk factor; ie, in-field (prostate bed, pelvic lymph nodes) or out-of-field (visceral or skeletal). It would be of great interest to know the pattern of CR, which can inform clinical decision-making to develop new or modified treatment regimens.

This study provides clinically useful information about when to use concomitant ADT and for how long. Even a short course of ADT can be associated with prolonged adverse effects in some men. Thus, safely avoiding hormonal suppression should be the goal in all men with prostate cancer, whether it is during primary or salvage radiation therapy.