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

• Published in: Journal of clinical oncology Vol. 38; no. 26; pp. 3024 - 3031
• Main Authors: Jackson, William C., Hartman, Holly E., Dess, Robert T., Birer, Sam R., Soni, Payal D., Hearn, Jason W.D., Reichert, Zachary R., Kishan, Amar U., Mahal, Brandon A., Zumsteg, Zachary S., Efstathiou, Jason A., Kaffenberger, Samuel, Morgan, Todd M., Mehra, Rohit, Showalter, Timothy N., Krauss, Daniel A., Nguyen, Paul L., Schipper, Matthew J., Feng, Felix Y., Sandler, Howard M., Hoskin, Peter J., Roach, Mack, Spratt, Daniel E.
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.09.2020
• Subjects: Aged; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Brachytherapy - adverse effects; Brachytherapy - mortality; Chemoradiotherapy - adverse effects; Chemoradiotherapy - mortality; Humans; Male; ORIGINAL REPORTS; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Radiation Dosage; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.19.03217

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. 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. 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. 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.