Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials

Abstract

PURPOSE In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. RESULTS Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. CONCLUSION Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.

Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis

“…While bRFS was superior in the CHHIP trial, the relative number of high-risk patients was lower than in our own patient cohort (12% vs. 41%) [ 2 , 20 ]. Interestingly, for the subgroup of high-risk patients in our cohort, the 5‑year bRFS was significantly increased with androgen deprivation therapy (ADT; 5‑year bRFS 90.9% vs. 55.4%, p = 0.008), which clearly underlines the importance of ADT in the high-risk group [ 21 , 22 ], despite treatment with escalated radiotherapy doses. In contrast, the sequence of ADT and radiotherapy appears to be less important [ 23 ].…”

A Review on the Current Treatment Paradigm in High-Risk Prostate Cancer

“…The utility of combining ADT with radiotherapy has often been questioned, especially in the setting of dose escalation. In fact, NCCN guidelines for both high-and very high risk prostate cancer include ADT as an option, rather than necessity, when EBRT is combined with low dose rate (LDR) brachytherapy boost [4]; however, a recent network meta-analysis suggests that EBRT and ADT may result in superior overall survival compared to patients treated with EBRT and brachytherapy boost (HR 0.68, 95% CI: 0.52-0.89) [39]. In the DART01/05 GICOR study, where about 50% patients belonged to the high-risk category, 28 months of long-term ADT combined with 78 Gy of external beam radiotherapy (EBRT) was associated with significantly superior overall and metastasis-free survival compared to 4 months of ADT with same dose of EBRT [40].…”

Trends in Androgen Deprivation Use in Men With Intermediate-Risk Prostate Cancer Who Underwent Radiation Therapy

“…Furthermore, a recent systematic review of predominantly intermediate and high risk localized prostate cancer suggests that patients receiving EBRT+BT without ADT may have inferior overall survival compared to EBRT alone in combination with ADT. 17 It is unclear why overall ADT use decreased from 2004-2009, although this may reflect multifactorial concerns regarding the morbidity of associated side effects, impact on quality of life, risk of cardiac toxicity, or unclear therapeutic benefit. [18][19][20][21] The increased incorporation of ADT with definitive radiotherapy may reflect clinical adoption following seminal trials demonstrating overall survival benefit with short term ADT prior to dose escalated radiotherapy.…”