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Extremely Dose Escalated Radiation Therapy Improves Cancer-Specific Survival Compared With Radical Prostatectomy or Conventionally Dose-Escalated Radiation Therapy in Gleason Score 9-10 Prostate Adenocarcinoma: A Multi-institutional Analysis of 1403 Patie

Kishan, A. U. and Ciezki, J. P. and Ross, A. E. and Cook, R. R. and Shaikh, T. and Stock, R. G. and Merrick, G. S. and Demanes, D. J. and Alam, R. and Spratt, D. E. and Abu-Isa, E. I. and Wedde, T. and Lilleby, W. and Sandler, K. A. and Song, D. and Reddy, C. A. and Nickols, N. and Steinberg, M. L. and Horwitz, E. M. (2017) Extremely Dose Escalated Radiation Therapy Improves Cancer-Specific Survival Compared With Radical Prostatectomy or Conventionally Dose-Escalated Radiation Therapy in Gleason Score 9-10 Prostate Adenocarcinoma: A Multi-institutional Analysis of 1403 Patie. International Journal of Radiation Oncology Biology Physics, 99 (2). S131. ISSN 0360-3016. https://resolver.caltech.edu/CaltechAUTHORS:20171114-073141158

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Abstract

Purpose/Objective(s): To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (PCa) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Materials/Methods: One thousand four hundred three patients with biopsy GS 9-10 PCa who received definitive treatment between 2000 and 2013 were included (506 treated with EBRT, 392 with EBRT+BT, and 505 with RP). Distant metastasis-free survival (DMFS) and prostate cancer-specific mortality (PCSM) were compared across the three cohorts with four cause-specific Cox regression models: (a) unadjusted, (b) covariate-adjusted for age, ln(iPSA), cT stage, and GS, (c) propensity score adjusted for the same covariates, and (d) in a doubly robust analysis (i.e., propensity score and covariate adjusted). Four analogous Fine and Gray competing risk models were developed to compare cumulative PCSM incidence. Results: The median follow-up period was 5.1 years (5.1, 6.4, and 4.3 years in the EBRT, EBRT + BT, and RP cohorts, respectively). The median doses among EBRT and EBRT+BT patients were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions, respectively. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 23 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT; 78% of postoperative RT was delivered in the salvage setting. PCSM was significantly lower among EBRT+BT patients than among either EBRT or RP patients in all cause-specific hazard models and Fine and Gray competing risk models, including unadjusted models (P<0.05 in unadjusted models and P<0.01 in all other models). PCSM was not significantly different between EBRT and RP patients in any model. DMFS was also significantly higher among patients treated with EBRT+BT in all cause-specific hazard models. In all adjusted models, DMFS was significantly superior among EBRT patients than RP patients (P<0.05). Five- and 10-year cumulative incidences of PCSM were 3% and 12% with EBRT+BT, 10% and 20% with EBRT, and 9% and 19% with RP, respectively (P<0.001). Overall survival was not significantly different between cohorts. Conclusion: In this multi-institutional consortium comprising over 1400 patients with GS 9-10 PCa, extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP in multiple models. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT cohort. This is hypothesis generating and suggests that improved local control via dose-escalation may have systemic control and survival implications even for patients with very high risk disease.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.ijrobp.2017.06.306DOIArticle
http://www.sciencedirect.com/science/article/pii/S0360301617313585PublisherArticle
Additional Information:© 2017 Published by Elsevier Inc. Available online 23 September 2017. Author Disclosure: A.U. Kishan: None. J.P. Ciezki: None. A.E. Ross: Consultant agreement ended 2014, currently conducting collaborative research; GenomeDx. Consultant; GenomeDx. R.R. Cook: None. T. Shaikh: None. R.G. Stock: Independent Contractor; BARD. Honoraria; BARD. G.S. Merrick: None. D. Demanes: Assist President in Society Duties; American College of Radiology - CARROS. R. Alam: None. D.E. Spratt: None. E.I. Abu-Isa: None. T. Wedde: None. W. Lilleby: None. K.A. Sandler: None. D. Song: Stock; Eli Lilly, Roche. C.A. Reddy: None. N. Nickols: Research Grant; Janssen LLC, Nanobiotix, Varian Medical Systems. Stock; GeneSciences Inc. Stock Options; GeneSciences Inc. M.L. Steinberg: Honoraria; Accuray. E.M. Horwitz: None. C.R. King: None.
Funders:
Funding AgencyGrant Number
Janssen LLCUNSPECIFIED
NanobiotixUNSPECIFIED
Varian Medical SystemsUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20171114-073141158
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20171114-073141158
Official Citation:A.U. Kishan, J.P. Ciezki, A.E. Ross, R.R. Cook, T. Shaikh, R.G. Stock, G.S. Merrick, D.J. Demanes, R. Alam, D.E. Spratt, E.I. Abu-Isa, T. Wedde, W. Lilleby, K.A. Sandler, D. Song, C.A. Reddy, N. Nickols, M.L. Steinberg, E.M. Horwitz, C.R. King, Extremely Dose Escalated Radiation Therapy Improves Cancer-Specific Survival Compared With Radical Prostatectomy or Conventionally Dose-Escalated Radiation Therapy in Gleason Score 9-10 Prostate Adenocarcinoma: A Multi-institutional Analysis of 1403 Patie, In International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement, 2017, Page S131, ISSN 0360-3016, https://doi.org/10.1016/j.ijrobp.2017.06.306. (http://www.sciencedirect.com/science/article/pii/S0360301617313585)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83183
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 Nov 2017 19:31
Last Modified:03 Oct 2019 19:03

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