Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

ABSTRACT Purpose The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) remains understudied, with limited long‐term data from large cohorts inclusive of both salvage radiotherapy (SRT)‐treated and untreated patients. Herein, we sought to evaluate the outcomes of patien...

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Main Authors: Spyridon P. Basourakos, Stephen A. Boorjian, Phillip J. Schulte, Grant Henning, Jamie T. O'Byrne, Matthew K. Tollefson, Igor Frank, Abhinav Khanna, Ryan M. Phillips, Bradley J. Stish, R. Jeffrey Karnes, Vidit Sharma
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Language:English
Published: Wiley 2025-07-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70988
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author Spyridon P. Basourakos
Stephen A. Boorjian
Phillip J. Schulte
Grant Henning
Jamie T. O'Byrne
Matthew K. Tollefson
Igor Frank
Abhinav Khanna
Ryan M. Phillips
Bradley J. Stish
R. Jeffrey Karnes
Vidit Sharma
author_facet Spyridon P. Basourakos
Stephen A. Boorjian
Phillip J. Schulte
Grant Henning
Jamie T. O'Byrne
Matthew K. Tollefson
Igor Frank
Abhinav Khanna
Ryan M. Phillips
Bradley J. Stish
R. Jeffrey Karnes
Vidit Sharma
author_sort Spyridon P. Basourakos
collection DOAJ
description ABSTRACT Purpose The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) remains understudied, with limited long‐term data from large cohorts inclusive of both salvage radiotherapy (SRT)‐treated and untreated patients. Herein, we sought to evaluate the outcomes of patients with BCR and the impact of SRT on disease progression. Materials and Methods Patients undergoing RP who developed BCR (PSA ≥ 0.20 ng/mL) were included. Patients with BCR treated with SRT were compared to untreated patients using risk‐set matching with time‐dependent propensity scores. The primary outcome was metastases, analyzed using Kaplan–Meier and Cox models. The number needed to treat (NNT) with SRT to prevent progression was derived at 5 and 15 years. Results Among 6881 patients with BCR, 2109 received SRT. At a median follow‐up of 10.2 years, 1147 patients developed metastases. The median PSA at the time of SRT was 0.50 ng/mL. After 1:1 propensity score matching (2109 patients per cohort), SRT significantly reduced the risk of metastases at 5 (12.7% vs. 19.3%, p < 0.0001) and 15 years (28.6% vs. 31.5%, p < 0.001). On multivariable analysis, SRT independently reduced metastasis risk (HR 0.75, 95% CI 0.63–0.90, p = 0.002), translating to NNT of 23 and 15 at 5 and 15 years, respectively. Interaction analyses between SRT and nodal status (p = 0.04) showed greater metastasis risk reduction in pN+ (HR 0.41, 95% CI 0.22–0.77, p = 0.005) compared to pN− disease (HR 0.81, 95% CI 0.67–0.97, p = 0.02). Conclusions Most patients with BCR post‐RP do not progress to metastasis. For those who do progress, SRT inarguably improves the oncologic outcomes in the BCR setting. However, careful patient selection and shared decision making should be encouraged in order to limit overtreatment and side effects.
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spelling doaj-art-60c4e562cbda48888e47639a046631442025-08-20T03:34:09ZengWileyCancer Medicine2045-76342025-07-011413n/an/a10.1002/cam4.70988Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical ProstatectomySpyridon P. Basourakos0Stephen A. Boorjian1Phillip J. Schulte2Grant Henning3Jamie T. O'Byrne4Matthew K. Tollefson5Igor Frank6Abhinav Khanna7Ryan M. Phillips8Bradley J. Stish9R. Jeffrey Karnes10Vidit Sharma11Department of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Health Sciences Research Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Health Sciences Research Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Radiation Oncology Mayo Clinic Rochester Minnesota USADepartment of Radiation Oncology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USAABSTRACT Purpose The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) remains understudied, with limited long‐term data from large cohorts inclusive of both salvage radiotherapy (SRT)‐treated and untreated patients. Herein, we sought to evaluate the outcomes of patients with BCR and the impact of SRT on disease progression. Materials and Methods Patients undergoing RP who developed BCR (PSA ≥ 0.20 ng/mL) were included. Patients with BCR treated with SRT were compared to untreated patients using risk‐set matching with time‐dependent propensity scores. The primary outcome was metastases, analyzed using Kaplan–Meier and Cox models. The number needed to treat (NNT) with SRT to prevent progression was derived at 5 and 15 years. Results Among 6881 patients with BCR, 2109 received SRT. At a median follow‐up of 10.2 years, 1147 patients developed metastases. The median PSA at the time of SRT was 0.50 ng/mL. After 1:1 propensity score matching (2109 patients per cohort), SRT significantly reduced the risk of metastases at 5 (12.7% vs. 19.3%, p < 0.0001) and 15 years (28.6% vs. 31.5%, p < 0.001). On multivariable analysis, SRT independently reduced metastasis risk (HR 0.75, 95% CI 0.63–0.90, p = 0.002), translating to NNT of 23 and 15 at 5 and 15 years, respectively. Interaction analyses between SRT and nodal status (p = 0.04) showed greater metastasis risk reduction in pN+ (HR 0.41, 95% CI 0.22–0.77, p = 0.005) compared to pN− disease (HR 0.81, 95% CI 0.67–0.97, p = 0.02). Conclusions Most patients with BCR post‐RP do not progress to metastasis. For those who do progress, SRT inarguably improves the oncologic outcomes in the BCR setting. However, careful patient selection and shared decision making should be encouraged in order to limit overtreatment and side effects.https://doi.org/10.1002/cam4.70988biochemical recurrenceprostate cancersalvage radiation therapy
spellingShingle Spyridon P. Basourakos
Stephen A. Boorjian
Phillip J. Schulte
Grant Henning
Jamie T. O'Byrne
Matthew K. Tollefson
Igor Frank
Abhinav Khanna
Ryan M. Phillips
Bradley J. Stish
R. Jeffrey Karnes
Vidit Sharma
Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
Cancer Medicine
biochemical recurrence
prostate cancer
salvage radiation therapy
title Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
title_full Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
title_fullStr Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
title_full_unstemmed Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
title_short Understanding the Impact of Salvage Radiation on the Long‐Term Natural History of Biochemically Recurrent Prostate Cancer After Radical Prostatectomy
title_sort understanding the impact of salvage radiation on the long term natural history of biochemically recurrent prostate cancer after radical prostatectomy
topic biochemical recurrence
prostate cancer
salvage radiation therapy
url https://doi.org/10.1002/cam4.70988
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