Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study

Nicola Fossati, Daniele Robesti, Robert Jeffrey Karnes, Matteo Soligo, Stephen A. Boorjian, Alberto Bossi, Gabriele Coraggio, Nadia Di Muzio, Cesare Cozzarini, Barbara Noris Chiorda, Giorgio Gandaglia, Simone Scarcella, Detlef Bartkowiak, Dirk Böhmer, Shahrokh Shariat, Gregor Goldner, Antonino Battaglia, Steven Joniau, Karin Haustermans, Gert De MeerleerValérie Fonteyne, Piet Ost, Hein Van Poppel, Francesco Montorsi, Thomas Wiegel, Alberto Briganti

Research output: Contribution to journalArticle

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Abstract

Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1 ng/ml at 1 mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8 yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9 mo. At median follow-up of 93 mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p = 0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p = 0.001; 0 vs ≥2, p < 0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36 mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12 mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. Patient summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT. The oncological benefit of hormonal therapy (HT) duration among men receiving salvage radiation therapy for increasing prostate-specific antigen after radical prostatectomy depends on their clinical and pathological characteristics. Our data suggest a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.

Original languageEnglish (US)
JournalEuropean urology
DOIs
StatePublished - Jan 1 2019

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Salvage Therapy
Prostatectomy
Radiotherapy
Prostate-Specific Antigen
Therapeutics
Recurrence

Keywords

  • Biochemical tumor markers
  • Hormonal therapy
  • Neoplasm recurrence
  • Prostatic neoplasms
  • Radiotherapy
  • Salvage therapy

ASJC Scopus subject areas

  • Urology

Cite this

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy : Results from a Multi-Institutional Study. / Fossati, Nicola; Robesti, Daniele; Karnes, Robert Jeffrey; Soligo, Matteo; Boorjian, Stephen A.; Bossi, Alberto; Coraggio, Gabriele; Di Muzio, Nadia; Cozzarini, Cesare; Noris Chiorda, Barbara; Gandaglia, Giorgio; Scarcella, Simone; Bartkowiak, Detlef; Böhmer, Dirk; Shariat, Shahrokh; Goldner, Gregor; Battaglia, Antonino; Joniau, Steven; Haustermans, Karin; De Meerleer, Gert; Fonteyne, Valérie; Ost, Piet; Van Poppel, Hein; Montorsi, Francesco; Wiegel, Thomas; Briganti, Alberto.

In: European urology, 01.01.2019.

Research output: Contribution to journalArticle

Fossati, N, Robesti, D, Karnes, RJ, Soligo, M, Boorjian, SA, Bossi, A, Coraggio, G, Di Muzio, N, Cozzarini, C, Noris Chiorda, B, Gandaglia, G, Scarcella, S, Bartkowiak, D, Böhmer, D, Shariat, S, Goldner, G, Battaglia, A, Joniau, S, Haustermans, K, De Meerleer, G, Fonteyne, V, Ost, P, Van Poppel, H, Montorsi, F, Wiegel, T & Briganti, A 2019, 'Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study', European urology. https://doi.org/10.1016/j.eururo.2019.02.004
Fossati, Nicola ; Robesti, Daniele ; Karnes, Robert Jeffrey ; Soligo, Matteo ; Boorjian, Stephen A. ; Bossi, Alberto ; Coraggio, Gabriele ; Di Muzio, Nadia ; Cozzarini, Cesare ; Noris Chiorda, Barbara ; Gandaglia, Giorgio ; Scarcella, Simone ; Bartkowiak, Detlef ; Böhmer, Dirk ; Shariat, Shahrokh ; Goldner, Gregor ; Battaglia, Antonino ; Joniau, Steven ; Haustermans, Karin ; De Meerleer, Gert ; Fonteyne, Valérie ; Ost, Piet ; Van Poppel, Hein ; Montorsi, Francesco ; Wiegel, Thomas ; Briganti, Alberto. / Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy : Results from a Multi-Institutional Study. In: European urology. 2019.
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abstract = "Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1 ng/ml at 1 mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8 yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitations: Overall, 1125 men (89{\%}) received SRT for rising PSA and 139 (11{\%}) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29{\%}), with a median HT duration of 9 mo. At median follow-up of 93 mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92{\%}. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p = 0.022). A total of 531 (42{\%}) patients had none of the prespecified risk factors, while 507 (40{\%}) had one and 226 (18{\%}) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p = 0.001; 0 vs ≥2, p < 0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36 mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12 mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. Patient summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT. The oncological benefit of hormonal therapy (HT) duration among men receiving salvage radiation therapy for increasing prostate-specific antigen after radical prostatectomy depends on their clinical and pathological characteristics. Our data suggest a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.",
keywords = "Biochemical tumor markers, Hormonal therapy, Neoplasm recurrence, Prostatic neoplasms, Radiotherapy, Salvage therapy",
author = "Nicola Fossati and Daniele Robesti and Karnes, {Robert Jeffrey} and Matteo Soligo and Boorjian, {Stephen A.} and Alberto Bossi and Gabriele Coraggio and {Di Muzio}, Nadia and Cesare Cozzarini and {Noris Chiorda}, Barbara and Giorgio Gandaglia and Simone Scarcella and Detlef Bartkowiak and Dirk B{\"o}hmer and Shahrokh Shariat and Gregor Goldner and Antonino Battaglia and Steven Joniau and Karin Haustermans and {De Meerleer}, Gert and Val{\'e}rie Fonteyne and Piet Ost and {Van Poppel}, Hein and Francesco Montorsi and Thomas Wiegel and Alberto Briganti",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.eururo.2019.02.004",
language = "English (US)",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",

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TY - JOUR

T1 - Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy

T2 - Results from a Multi-Institutional Study

AU - Fossati, Nicola

AU - Robesti, Daniele

AU - Karnes, Robert Jeffrey

AU - Soligo, Matteo

AU - Boorjian, Stephen A.

AU - Bossi, Alberto

AU - Coraggio, Gabriele

AU - Di Muzio, Nadia

AU - Cozzarini, Cesare

AU - Noris Chiorda, Barbara

AU - Gandaglia, Giorgio

AU - Scarcella, Simone

AU - Bartkowiak, Detlef

AU - Böhmer, Dirk

AU - Shariat, Shahrokh

AU - Goldner, Gregor

AU - Battaglia, Antonino

AU - Joniau, Steven

AU - Haustermans, Karin

AU - De Meerleer, Gert

AU - Fonteyne, Valérie

AU - Ost, Piet

AU - Van Poppel, Hein

AU - Montorsi, Francesco

AU - Wiegel, Thomas

AU - Briganti, Alberto

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1 ng/ml at 1 mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8 yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9 mo. At median follow-up of 93 mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p = 0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p = 0.001; 0 vs ≥2, p < 0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36 mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12 mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. Patient summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT. The oncological benefit of hormonal therapy (HT) duration among men receiving salvage radiation therapy for increasing prostate-specific antigen after radical prostatectomy depends on their clinical and pathological characteristics. Our data suggest a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.

AB - Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1 ng/ml at 1 mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8 yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9 mo. At median follow-up of 93 mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p = 0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p = 0.001; 0 vs ≥2, p < 0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36 mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12 mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. Patient summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT. The oncological benefit of hormonal therapy (HT) duration among men receiving salvage radiation therapy for increasing prostate-specific antigen after radical prostatectomy depends on their clinical and pathological characteristics. Our data suggest a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.

KW - Biochemical tumor markers

KW - Hormonal therapy

KW - Neoplasm recurrence

KW - Prostatic neoplasms

KW - Radiotherapy

KW - Salvage therapy

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