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.
Abstract | BACKGROUND: 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 11862 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:
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Authors | Amar U Kishan, Xiaoyan Wang, 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 Sydes, David 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, MARCAP Consortium |
Journal | European urology
(Eur Urol)
Vol. 82
Issue 1
Pg. 106-114
(07 2022)
ISSN: 1873-7560 [Electronic] Switzerland |
PMID | 35469702
(Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved. |
Chemical References |
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Topics |
- Androgen Antagonists
(therapeutic use)
- Bayes Theorem
- Hot Temperature
- Humans
- Male
- Multicenter Studies as Topic
- Network Meta-Analysis
- Prostatic Neoplasms
(drug therapy, radiotherapy)
- Quality of Life
- Radiotherapy
(adverse effects, methods)
- Radiotherapy Dosage
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