Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy

Nicola Fossati, Robert Jeffrey Karnes, Cesare Cozzarini, Claudio Fiorino, Giorgio Gandaglia, Steven Joniau, Stephen A. Boorjian, Gregor Goldner, Wolfgang Hinkelbein, Karin Haustermans, Bertrand Tombal, Shahrokh Shariat, Pierre I. Karakiewicz, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel, Alberto Briganti

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Abstract

Background Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. Objective To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. Design, setting, and participants The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Outcome measurements and statistical analysis Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥8, and negative surgical margins. Results and limitations Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p <0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. Conclusions In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. Patient summary In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Take Home Message Cancer control after early salvage radiation therapy (eSRT) depends on pretreatment prostate-specific antigen (PSA) level and is highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. Conversely, the benefit of eSRT is less evident in men with favourable disease at radical prostatectomy despite PSA rise.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalEuropean Urology
Volume69
Issue number4
DOIs
StatePublished - Apr 1 2016

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Salvage Therapy
Prostate-Specific Antigen
Prostatectomy
Secondary Prevention
Radiotherapy
Neoplasm Grading
Recurrence
Neoplasms
Retrospective Studies
Regression Analysis
Confidence Intervals

Keywords

  • Biochemical tumour markers
  • Neoplasm recurrence
  • Prostatic neoplasms
  • Radiotherapy
  • Salvage therapy

ASJC Scopus subject areas

  • Urology

Cite this

Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy. / Fossati, Nicola; Karnes, Robert Jeffrey; Cozzarini, Cesare; Fiorino, Claudio; Gandaglia, Giorgio; Joniau, Steven; Boorjian, Stephen A.; Goldner, Gregor; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Karakiewicz, Pierre I.; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto.

In: European Urology, Vol. 69, No. 4, 01.04.2016, p. 728-733.

Research output: Contribution to journalArticle

Fossati, N, Karnes, RJ, Cozzarini, C, Fiorino, C, Gandaglia, G, Joniau, S, Boorjian, SA, Goldner, G, Hinkelbein, W, Haustermans, K, Tombal, B, Shariat, S, Karakiewicz, PI, Montorsi, F, Van Poppel, H, Wiegel, T & Briganti, A 2016, 'Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy', European Urology, vol. 69, no. 4, pp. 728-733. https://doi.org/10.1016/j.eururo.2015.10.009
Fossati, Nicola ; Karnes, Robert Jeffrey ; Cozzarini, Cesare ; Fiorino, Claudio ; Gandaglia, Giorgio ; Joniau, Steven ; Boorjian, Stephen A. ; Goldner, Gregor ; Hinkelbein, Wolfgang ; Haustermans, Karin ; Tombal, Bertrand ; Shariat, Shahrokh ; Karakiewicz, Pierre I. ; Montorsi, Francesco ; Van Poppel, Hein ; Wiegel, Thomas ; Briganti, Alberto. / Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy. In: European Urology. 2016 ; Vol. 69, No. 4. pp. 728-733.
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abstract = "Background Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. Objective To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. Design, setting, and participants The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Outcome measurements and statistical analysis Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥8, and negative surgical margins. Results and limitations Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82{\%} (95{\%} confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95{\%} CI, 1.40-22.9; p <0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10{\%} per 0.1 ng/ml of PSA level compared with only 1.5{\%} in patients with one or no pathologic risk factors. Conclusions In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. Patient summary In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Take Home Message Cancer control after early salvage radiation therapy (eSRT) depends on pretreatment prostate-specific antigen (PSA) level and is highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. Conversely, the benefit of eSRT is less evident in men with favourable disease at radical prostatectomy despite PSA rise.",
keywords = "Biochemical tumour markers, Neoplasm recurrence, Prostatic neoplasms, Radiotherapy, Salvage therapy",
author = "Nicola Fossati and Karnes, {Robert Jeffrey} and Cesare Cozzarini and Claudio Fiorino and Giorgio Gandaglia and Steven Joniau and Boorjian, {Stephen A.} and Gregor Goldner and Wolfgang Hinkelbein and Karin Haustermans and Bertrand Tombal and Shahrokh Shariat and Karakiewicz, {Pierre I.} and Francesco Montorsi and {Van Poppel}, Hein and Thomas Wiegel and Alberto Briganti",
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TY - JOUR

T1 - Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy

AU - Fossati, Nicola

AU - Karnes, Robert Jeffrey

AU - Cozzarini, Cesare

AU - Fiorino, Claudio

AU - Gandaglia, Giorgio

AU - Joniau, Steven

AU - Boorjian, Stephen A.

AU - Goldner, Gregor

AU - Hinkelbein, Wolfgang

AU - Haustermans, Karin

AU - Tombal, Bertrand

AU - Shariat, Shahrokh

AU - Karakiewicz, Pierre I.

AU - Montorsi, Francesco

AU - Van Poppel, Hein

AU - Wiegel, Thomas

AU - Briganti, Alberto

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. Objective To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. Design, setting, and participants The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Outcome measurements and statistical analysis Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥8, and negative surgical margins. Results and limitations Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p <0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. Conclusions In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. Patient summary In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Take Home Message Cancer control after early salvage radiation therapy (eSRT) depends on pretreatment prostate-specific antigen (PSA) level and is highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. Conversely, the benefit of eSRT is less evident in men with favourable disease at radical prostatectomy despite PSA rise.

AB - Background Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. Objective To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. Design, setting, and participants The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Outcome measurements and statistical analysis Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥8, and negative surgical margins. Results and limitations Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p <0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. Conclusions In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. Patient summary In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Take Home Message Cancer control after early salvage radiation therapy (eSRT) depends on pretreatment prostate-specific antigen (PSA) level and is highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. Conversely, the benefit of eSRT is less evident in men with favourable disease at radical prostatectomy despite PSA rise.

KW - Biochemical tumour markers

KW - Neoplasm recurrence

KW - Prostatic neoplasms

KW - Radiotherapy

KW - Salvage therapy

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