Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features

William L. Hwang, Rahul D. Tendulkar, Andrzej Niemierko, Shree Agrawal, Kevin L. Stephans, Daniel E. Spratt, Jason W. Hearn, Bridget F. Koontz, W. Robert Lee, Jeff M. Michalski, Thomas M. Pisansky, Stanley L. Liauw, Matthew C Abramowitz, Alan Pollack, Drew Moghanaki, Mitchell S. Anscher, Robert B. Den, Anthony L. Zietman, Andrew J. Stephenson, Jason A. Efstathiou

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Original languageEnglish (US)
Article number2670381
JournalJAMA oncology
Volume4
Issue number5
DOIs
StatePublished - May 1 2018

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Adjuvant Radiotherapy
Prostatic Neoplasms
Radiotherapy
Propensity Score
Prostate-Specific Antigen
Prostatectomy
Neoplasm Metastasis
Recurrence
Nomograms
Survival
Neoplasm Grading
Androgens
Cohort Studies
Multivariate Analysis
Outcome Assessment (Health Care)
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hwang, W. L., Tendulkar, R. D., Niemierko, A., Agrawal, S., Stephans, K. L., Spratt, D. E., ... Efstathiou, J. A. (2018). Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features. JAMA oncology, 4(5), [2670381]. https://doi.org/10.1001/jamaoncol.2017.5230

Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features. / Hwang, William L.; Tendulkar, Rahul D.; Niemierko, Andrzej; Agrawal, Shree; Stephans, Kevin L.; Spratt, Daniel E.; Hearn, Jason W.; Koontz, Bridget F.; Lee, W. Robert; Michalski, Jeff M.; Pisansky, Thomas M.; Liauw, Stanley L.; Abramowitz, Matthew C; Pollack, Alan; Moghanaki, Drew; Anscher, Mitchell S.; Den, Robert B.; Zietman, Anthony L.; Stephenson, Andrew J.; Efstathiou, Jason A.

In: JAMA oncology, Vol. 4, No. 5, 2670381, 01.05.2018.

Research output: Contribution to journalArticle

Hwang, WL, Tendulkar, RD, Niemierko, A, Agrawal, S, Stephans, KL, Spratt, DE, Hearn, JW, Koontz, BF, Lee, WR, Michalski, JM, Pisansky, TM, Liauw, SL, Abramowitz, MC, Pollack, A, Moghanaki, D, Anscher, MS, Den, RB, Zietman, AL, Stephenson, AJ & Efstathiou, JA 2018, 'Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features', JAMA oncology, vol. 4, no. 5, 2670381. https://doi.org/10.1001/jamaoncol.2017.5230
Hwang, William L. ; Tendulkar, Rahul D. ; Niemierko, Andrzej ; Agrawal, Shree ; Stephans, Kevin L. ; Spratt, Daniel E. ; Hearn, Jason W. ; Koontz, Bridget F. ; Lee, W. Robert ; Michalski, Jeff M. ; Pisansky, Thomas M. ; Liauw, Stanley L. ; Abramowitz, Matthew C ; Pollack, Alan ; Moghanaki, Drew ; Anscher, Mitchell S. ; Den, Robert B. ; Zietman, Anthony L. ; Stephenson, Andrew J. ; Efstathiou, Jason A. / Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features. In: JAMA oncology. 2018 ; Vol. 4, No. 5.
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abstract = "IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69{\%} [95{\%} CI, 60{\%}-76{\%}] vs 43{\%} [95{\%} CI, 35{\%}-51{\%}]; effect size, 26{\%}), freedom from distant metastases (95{\%} [95{\%} CI, 90{\%}-97{\%}] vs 85{\%} [95{\%} CI, 76{\%}-90{\%}]; effect size, 10{\%}), and overall survival (91{\%} [95{\%} CI, 84{\%}-95{\%}] vs 79{\%} [95{\%} CI, 69{\%}-86{\%}]; effect size, 12{\%}). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56{\%} of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33{\%} to 52{\%} after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.",
author = "Hwang, {William L.} and Tendulkar, {Rahul D.} and Andrzej Niemierko and Shree Agrawal and Stephans, {Kevin L.} and Spratt, {Daniel E.} and Hearn, {Jason W.} and Koontz, {Bridget F.} and Lee, {W. Robert} and Michalski, {Jeff M.} and Pisansky, {Thomas M.} and Liauw, {Stanley L.} and Abramowitz, {Matthew C} and Alan Pollack and Drew Moghanaki and Anscher, {Mitchell S.} and Den, {Robert B.} and Zietman, {Anthony L.} and Stephenson, {Andrew J.} and Efstathiou, {Jason A.}",
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T1 - Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features

AU - Hwang, William L.

AU - Tendulkar, Rahul D.

AU - Niemierko, Andrzej

AU - Agrawal, Shree

AU - Stephans, Kevin L.

AU - Spratt, Daniel E.

AU - Hearn, Jason W.

AU - Koontz, Bridget F.

AU - Lee, W. Robert

AU - Michalski, Jeff M.

AU - Pisansky, Thomas M.

AU - Liauw, Stanley L.

AU - Abramowitz, Matthew C

AU - Pollack, Alan

AU - Moghanaki, Drew

AU - Anscher, Mitchell S.

AU - Den, Robert B.

AU - Zietman, Anthony L.

AU - Stephenson, Andrew J.

AU - Efstathiou, Jason A.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

AB - IMPORTANCE Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. OBJECTIVE To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. DESIGN, SETTING, AND PARTICIPANTS This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. MAIN OUTCOMES AND MEASURES Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. RESULTS Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. CONCLUSIONS AND RELEVANCE Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

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