Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

Thomas M. Pisansky, Shree Agrawal, Daniel A. Hamstra, Bridget F. Koontz, Stanley L. Liauw, Jason A. Efstathiou, Jeff M. Michalski, Felix Y. Feng, Matthew C Abramowitz, Alan Pollack, Mitchell S. Anscher, Drew Moghanaki, Robert B. Den, Kevin L. Stephans, Anthony L. Zietman, W. Robert Lee, Michael W. Kattan, Andrew J. Stephenson, Rahul D. Tendulkar

Research output: Contribution to journalArticle

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Abstract

Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

Original languageEnglish (US)
Pages (from-to)1046-1053
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume96
Issue number5
DOIs
StatePublished - Dec 1 2016

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Salvage Therapy
metastasis
Observational Studies
radiation therapy
Prostatic Neoplasms
Radiotherapy
cancer
Neoplasm Metastasis
antigens
dosage
Prostate-Specific Antigen
Radiation
incidence
radiation
Incidence
tumors
Neoplasm Grading
Seminal Vesicles
Prostatectomy
Proportional Hazards Models

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study. / Pisansky, Thomas M.; Agrawal, Shree; Hamstra, Daniel A.; Koontz, Bridget F.; Liauw, Stanley L.; Efstathiou, Jason A.; Michalski, Jeff M.; Feng, Felix Y.; Abramowitz, Matthew C; Pollack, Alan; Anscher, Mitchell S.; Moghanaki, Drew; Den, Robert B.; Stephans, Kevin L.; Zietman, Anthony L.; Lee, W. Robert; Kattan, Michael W.; Stephenson, Andrew J.; Tendulkar, Rahul D.

In: International Journal of Radiation Oncology Biology Physics, Vol. 96, No. 5, 01.12.2016, p. 1046-1053.

Research output: Contribution to journalArticle

Pisansky, TM, Agrawal, S, Hamstra, DA, Koontz, BF, Liauw, SL, Efstathiou, JA, Michalski, JM, Feng, FY, Abramowitz, MC, Pollack, A, Anscher, MS, Moghanaki, D, Den, RB, Stephans, KL, Zietman, AL, Lee, WR, Kattan, MW, Stephenson, AJ & Tendulkar, RD 2016, 'Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study', International Journal of Radiation Oncology Biology Physics, vol. 96, no. 5, pp. 1046-1053. https://doi.org/10.1016/j.ijrobp.2016.08.043
Pisansky, Thomas M. ; Agrawal, Shree ; Hamstra, Daniel A. ; Koontz, Bridget F. ; Liauw, Stanley L. ; Efstathiou, Jason A. ; Michalski, Jeff M. ; Feng, Felix Y. ; Abramowitz, Matthew C ; Pollack, Alan ; Anscher, Mitchell S. ; Moghanaki, Drew ; Den, Robert B. ; Stephans, Kevin L. ; Zietman, Anthony L. ; Lee, W. Robert ; Kattan, Michael W. ; Stephenson, Andrew J. ; Tendulkar, Rahul D. / Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study. In: International Journal of Radiation Oncology Biology Physics. 2016 ; Vol. 96, No. 5. pp. 1046-1053.
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abstract = "Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5{\%} and 49.8{\%}, respectively, and the cumulative incidence of distant metastasis was 12.4{\%} by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.",
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T1 - Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

AU - Pisansky, Thomas M.

AU - Agrawal, Shree

AU - Hamstra, Daniel A.

AU - Koontz, Bridget F.

AU - Liauw, Stanley L.

AU - Efstathiou, Jason A.

AU - Michalski, Jeff M.

AU - Feng, Felix Y.

AU - Abramowitz, Matthew C

AU - Pollack, Alan

AU - Anscher, Mitchell S.

AU - Moghanaki, Drew

AU - Den, Robert B.

AU - Stephans, Kevin L.

AU - Zietman, Anthony L.

AU - Lee, W. Robert

AU - Kattan, Michael W.

AU - Stephenson, Andrew J.

AU - Tendulkar, Rahul D.

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N2 - Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

AB - Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

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