Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series

Nicola Fossati, Robert Jeffrey Karnes, Stephen A. Boorjian, Marco Moschini, Alessandro Morlacco, Alberto Bossi, Thomas Seisen, Cesare Cozzarini, Claudio Fiorino, Barbara Noris Chiorda, Giorgio Gandaglia, Paolo Dell'Oglio, Steven Joniau, Lorenzo Tosco, Shahrokh Shariat, Gregor Goldner, Wolfgang Hinkelbein, Detlef Bartkowiak, Karin Haustermans, Bertrand TombalFrancesco Montorsi, Hein Van Poppel, Thomas Wiegel, Alberto Briganti

Research output: Contribution to journalArticle

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Abstract

Background: Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). Objective: To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Design, setting, and participants: Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5. ng/ml. Intervention: We compared aRT versus observation followed by esRT. Outcome measurements and statistical analysis: The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Results and limitations: Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p = 0.2). MFS (92% vs 91%; . p = 0.9) and OS (89% vs 92%; . p = 0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; . p = 0.4) and overall mortality (HR: 1.39; . p = 0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p = 0.9 and . p = 0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. Conclusions: At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Patient summary: At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. In this retrospective study, early salvage radiation therapy (esRT) provided comparable metastasis-free and overall survival with adjuvant radiation therapy (aRT) at long-term follow-up. A management approach to patients with adverse pathology at radical prostatectomy with initial observation and then esRT if biochemical relapse is diagnosed may not compromise cancer control and may reduce the overtreatment associated with a strategy of administering aRT to all such patients.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2016

Fingerprint

Salvage Therapy
Prostatectomy
Secondary Prevention
Prostatic Neoplasms
Radiotherapy
Survival
Observation
Neoplasm Metastasis
Prostate-Specific Antigen
Recurrence
Neoplasms

Keywords

  • Adjuvant
  • Prostatic neoplasms
  • Radiation therapy
  • Salvage therapy

ASJC Scopus subject areas

  • Urology

Cite this

Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy : Results from a Multi-institutional Series. / Fossati, Nicola; Karnes, Robert Jeffrey; Boorjian, Stephen A.; Moschini, Marco; Morlacco, Alessandro; Bossi, Alberto; Seisen, Thomas; Cozzarini, Cesare; Fiorino, Claudio; Chiorda, Barbara Noris; Gandaglia, Giorgio; Dell'Oglio, Paolo; Joniau, Steven; Tosco, Lorenzo; Shariat, Shahrokh; Goldner, Gregor; Hinkelbein, Wolfgang; Bartkowiak, Detlef; Haustermans, Karin; Tombal, Bertrand; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto.

In: European Urology, 2016.

Research output: Contribution to journalArticle

Fossati, N, Karnes, RJ, Boorjian, SA, Moschini, M, Morlacco, A, Bossi, A, Seisen, T, Cozzarini, C, Fiorino, C, Chiorda, BN, Gandaglia, G, Dell'Oglio, P, Joniau, S, Tosco, L, Shariat, S, Goldner, G, Hinkelbein, W, Bartkowiak, D, Haustermans, K, Tombal, B, Montorsi, F, Van Poppel, H, Wiegel, T & Briganti, A 2016, 'Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series', European Urology. https://doi.org/10.1016/j.eururo.2016.07.028
Fossati, Nicola ; Karnes, Robert Jeffrey ; Boorjian, Stephen A. ; Moschini, Marco ; Morlacco, Alessandro ; Bossi, Alberto ; Seisen, Thomas ; Cozzarini, Cesare ; Fiorino, Claudio ; Chiorda, Barbara Noris ; Gandaglia, Giorgio ; Dell'Oglio, Paolo ; Joniau, Steven ; Tosco, Lorenzo ; Shariat, Shahrokh ; Goldner, Gregor ; Hinkelbein, Wolfgang ; Bartkowiak, Detlef ; Haustermans, Karin ; Tombal, Bertrand ; Montorsi, Francesco ; Van Poppel, Hein ; Wiegel, Thomas ; Briganti, Alberto. / Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy : Results from a Multi-institutional Series. In: European Urology. 2016.
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title = "Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series",
abstract = "Background: Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). Objective: To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Design, setting, and participants: Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5. ng/ml. Intervention: We compared aRT versus observation followed by esRT. Outcome measurements and statistical analysis: The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Results and limitations: Overall, 243 patients (48{\%}) underwent aRT, and 267 (52{\%}) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p = 0.2). MFS (92{\%} vs 91{\%}; . p = 0.9) and OS (89{\%} vs 92{\%}; . p = 0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; . p = 0.4) and overall mortality (HR: 1.39; . p = 0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p = 0.9 and . p = 0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. Conclusions: At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Patient summary: At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. In this retrospective study, early salvage radiation therapy (esRT) provided comparable metastasis-free and overall survival with adjuvant radiation therapy (aRT) at long-term follow-up. A management approach to patients with adverse pathology at radical prostatectomy with initial observation and then esRT if biochemical relapse is diagnosed may not compromise cancer control and may reduce the overtreatment associated with a strategy of administering aRT to all such patients.",
keywords = "Adjuvant, Prostatic neoplasms, Radiation therapy, Salvage therapy",
author = "Nicola Fossati and Karnes, {Robert Jeffrey} and Boorjian, {Stephen A.} and Marco Moschini and Alessandro Morlacco and Alberto Bossi and Thomas Seisen and Cesare Cozzarini and Claudio Fiorino and Chiorda, {Barbara Noris} and Giorgio Gandaglia and Paolo Dell'Oglio and Steven Joniau and Lorenzo Tosco and Shahrokh Shariat and Gregor Goldner and Wolfgang Hinkelbein and Detlef Bartkowiak and Karin Haustermans and Bertrand Tombal and Francesco Montorsi and {Van Poppel}, Hein and Thomas Wiegel and Alberto Briganti",
year = "2016",
doi = "10.1016/j.eururo.2016.07.028",
language = "English (US)",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",

}

TY - JOUR

T1 - Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy

T2 - Results from a Multi-institutional Series

AU - Fossati, Nicola

AU - Karnes, Robert Jeffrey

AU - Boorjian, Stephen A.

AU - Moschini, Marco

AU - Morlacco, Alessandro

AU - Bossi, Alberto

AU - Seisen, Thomas

AU - Cozzarini, Cesare

AU - Fiorino, Claudio

AU - Chiorda, Barbara Noris

AU - Gandaglia, Giorgio

AU - Dell'Oglio, Paolo

AU - Joniau, Steven

AU - Tosco, Lorenzo

AU - Shariat, Shahrokh

AU - Goldner, Gregor

AU - Hinkelbein, Wolfgang

AU - Bartkowiak, Detlef

AU - Haustermans, Karin

AU - Tombal, Bertrand

AU - Montorsi, Francesco

AU - Van Poppel, Hein

AU - Wiegel, Thomas

AU - Briganti, Alberto

PY - 2016

Y1 - 2016

N2 - Background: Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). Objective: To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Design, setting, and participants: Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5. ng/ml. Intervention: We compared aRT versus observation followed by esRT. Outcome measurements and statistical analysis: The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Results and limitations: Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p = 0.2). MFS (92% vs 91%; . p = 0.9) and OS (89% vs 92%; . p = 0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; . p = 0.4) and overall mortality (HR: 1.39; . p = 0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p = 0.9 and . p = 0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. Conclusions: At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Patient summary: At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. In this retrospective study, early salvage radiation therapy (esRT) provided comparable metastasis-free and overall survival with adjuvant radiation therapy (aRT) at long-term follow-up. A management approach to patients with adverse pathology at radical prostatectomy with initial observation and then esRT if biochemical relapse is diagnosed may not compromise cancer control and may reduce the overtreatment associated with a strategy of administering aRT to all such patients.

AB - Background: Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). Objective: To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Design, setting, and participants: Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5. ng/ml. Intervention: We compared aRT versus observation followed by esRT. Outcome measurements and statistical analysis: The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Results and limitations: Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p = 0.2). MFS (92% vs 91%; . p = 0.9) and OS (89% vs 92%; . p = 0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; . p = 0.4) and overall mortality (HR: 1.39; . p = 0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p = 0.9 and . p = 0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. Conclusions: At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Patient summary: At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. In this retrospective study, early salvage radiation therapy (esRT) provided comparable metastasis-free and overall survival with adjuvant radiation therapy (aRT) at long-term follow-up. A management approach to patients with adverse pathology at radical prostatectomy with initial observation and then esRT if biochemical relapse is diagnosed may not compromise cancer control and may reduce the overtreatment associated with a strategy of administering aRT to all such patients.

KW - Adjuvant

KW - Prostatic neoplasms

KW - Radiation therapy

KW - Salvage therapy

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SN - 0302-2838

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