High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient–data Network Meta-analysis from the MARCAP Consortium

Amar U. Kishan*, Xiaoyan Wang, Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators, Yilun Sun, Tahmineh Romero, Jeff M. Michalski, Ting Martin Ma, Felix Y. Feng, Howard M. Sandler, Michel Bolla, Philippe Maingon, Theo De Reijke, Anouk Neven, Allison Steigler, James W. Denham, David Joseph, Abdenour Nabid, Nathalie Carrier, Luis Souhami, Matt R. SydesDavid P. Dearnaley, Isabel Syndikus, Alison C. Tree, Luca Incrocci, Wilma D. Heemsbergen, Floris J. Pos, Almudena Zapatero, Jason A. Efstathiou, Araceli Guerrero, Ana Alvarez, Carmen Gonzalez San-Segundo, Xavier Maldonado, Michael Xiang, Matthew B. Rettig, Robert E. Reiter, Nicholas G. Zaorsky, Wee Loon Ong, Robert T. Dess, Michael L. Steinberg, Nicholas G. Nickols, Soumyajit Roy, Jorge A. Garcia, Daniel E. Spratt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)


Background: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown. Objective: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT. Design, setting, and participants: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11 862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT. Outcome measurements and statistical analyses: Metastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence–free survival (BCRFS). Results and limitations: Median follow-up was 8.8 yr (interquartile range 5.7–11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80–1.18) or with STADT (HR 0.99, 95% CI 0.8–1.23) or LTADT (HR 0.94, 95% CI 0.65–1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes. Conclusions: Conventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT. Patient summary: Using a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment.

Original languageEnglish
Pages (from-to)106-114
Number of pages9
JournalEuropean Urology
Issue number1
Early online date9 Jun 2022
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
Financial disclosures: Amar U. Kishan certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Amar U. Kishan has received personal fees from Varian Medical Systems, ViewRay, and Intelligent Automation; and research support from ViewRay and research support from the American Society for Radiation Oncology, the Prostate Cancer Foundation, and the Jonsson Comprehensive Cancer Center, all outside the submitted work. Felix Y. Feng has a consulting or advisory role for Astellas, Bayer, Blue Earth Diagnostics, Celgene, EMD Serono, Genentech, Janssen, Myovant, Ryovant, Bristol-Myers Squibb, Exact Sciences, Varian, Bluestar Genomics, and Serimmun, and has received research funding from Zenth Epigenetics. AN has received personal fees from AstraZeneca outside the submitted work. Luis Souhami has received personal fees from Sanofi Canada and Varian Medical Systems outside the submitted work. Jason A. Efstathiou has received personal fees from Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Taris Biomedical, Merck, Roviant Pharma, and Myovant Sciences. Howard M. Sandler is a member of a clinical trial steering committee for Janssen and has stock from Radiogel for an inactive role on medical advisory board, both outside of the submitted work. Matthew B. Rettig has received personal fees from Amgen, Clovis, Janssen, Bayer, and Abrx, and research support from Janssen and Merck outside the submitted work. NGN has received research funding from Janssen, Lantheus, and Bayer, and consulting fees from Oncolinea. Daniel E. Spratt has received personal fees from Janssen, AstraZeneca, and Blue Earth Diagnostics outside of the submitted work. The remaining authors have nothing to disclose.

Funding Information:
Funding/Support and role of the sponsor: This work was supported by funds from the American Society for Radiation Oncology, the Prostate Cancer Foundation, the US Department of Defense, and private donations. The sponsors played a role in the design and conduct of the study and in data analysis.

Publisher Copyright:
© 2022 European Association of Urology


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