- Title
- Local Failure Events in Prostate Cancer Treated with Radiotherapy: A Pooled Analysis of 18 Randomized Trials from the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium (LEVIATHAN)
- Creator
- Ma, Ting Martin; Chu, Fang-I; Bolla, Michel; de Reijke, Theo M.; Maingon, Philippe; Neven, Anouk; Denham, James; Steigler, Allison; Joseph, David J.; Nabid, Abdenour; Souhami, Luis; Carrier, Nathalie; Sandler, Howard; Incrocci, Luca; Heemsbergen, Wilma; Pos, Floris J.; Sydes, Matthew R.; Dearnaley, David P.; Tree, Alison C.; Syndikus, Isabel; Hall, Emma; Cruickshank, Clare; Malone, Shawn; Feng, Felix Y.; Roy, Soumyajit; Sun, Yilun; Zaorsky, Nicholas G.; Nickols, Nicholas G.; Reiter, Robert E.; Rettig, Matthew B.; Steinberg, Michael L.; Reddy, Vishruth K.; Xiang, Michael; Romero, Tahmineh; Efstathiou, Jason A.; Spratt, Daniel E.; Kishan, Amar U.; Meta-analysis of Randomized trials in Cancer of the Prostate MARCAP Consortium investigators,; Jones, Christopher U.; Roach, Mack; Rosenthal, Seth A.; Pisansky, Thomas; Michalski, Jeff M.
- Relation
- European Urology Vol. 82, Issue 5, p. 487-498
- Publisher Link
- http://dx.doi.org/10.1016/j.eururo.2022.07.011
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- Context: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. Objective: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. Evidence acquisition: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. Evidence synthesis: The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06– 1.30), PCSS (HR 2.02, 95% CI 1.75–2.33), and DMFS (HR 1.94, 95% CI 1.75–2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21–0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. Conclusions: Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a ‘‘second wave’’ of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. Patient summary: Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it.
- Subject
- distant metastasis; local control; local failure; pooled analysis; prostate cancer; radiation therapy; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1489331
- Identifier
- uon:52683
- Identifier
- ISSN:0302-2838
- Language
- eng
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