Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies

Karim A. Touijer, Robert Jeffrey Karnes, Niccolo Passoni, Daniel D. Sjoberg, Melissa Assel, Nicola Fossati, Giorgio Gandaglia, James A. Eastham, Peter T. Scardino, Andrew Vickers, Cesare Cozzarini, Francesco Montorsi, Alberto Briganti

Research output: Contribution to journalArticle

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Abstract

Background: Optimal management of patients with lymph node metastasis (LNM) after radical prostatectomy (RP) remains undefined. Objective: We evaluated the association between three different management strategies and survival in prostate cancer with LNM after RP. Design, setting, and participants: We analyzed data of 1338 patients with LNM after RP from three tertiary care centers. Three hundred and eighty-seven patients (28%) were observed, 676 (49%) received lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23%) received adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty-eight men were followed for more than 10 yr. Outcome measurements and statistical analysis: Primary outcome measure was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier methods were used to visualize OS for the three treatment groups. Cox proportional hazards regression was utilized to compare OS and CSS among the three groups. Results and limitations: ADT + EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66, p <. 0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p <. 0.0001). Higher-risk patients benefited more from ADT + EBRT than lower-risk patients. Ten-year mortality risk difference between ADT + EBRT, observation, or ADT alone ranged from 5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT + EBRT was also associated with better CSS than observation or ADT alone (p <. 0.0001), ADT had better CSS compared to observation (HR: 0.64, 95% CI: 0.43-0.95, p = 0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95% CI: 1.45-6.40, p = 0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95% CI: 0.65-1.25, p = 0.5). While selection bias might remain, its effect would operate in the opposite direction to our findings. Conclusions: In men with LNM after RP, ADT + EBRT improved survival over either observation or adjuvant ADT alone. This survival benefit increases with higher-risk disease. Patient summary: Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. However, we found that adjuvant androgen deprivation therapy with external beam radiation therapy improved survival in these patients. Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. Adjuvant androgen deprivation therapy with external beam radiation therapy confers a long-term overall survival advantage than either observation or androgen deprivation therapy alone.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2017

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Prostatectomy
Androgens
Prostatic Neoplasms
Lymph Nodes
Survival
Radiotherapy
Observation
Therapeutics
Neoplasm Metastasis
Confidence Intervals
Mortality
Neoplasms
Selection Bias
Tertiary Care Centers

Keywords

  • Adjuvant radiotherapy
  • Antineoplastic agents
  • Hormonal
  • Lymphatic metastasis
  • Mortality
  • Prognosis
  • Prostatectomy
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Urology

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Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy : A Comparative Analysis of Different Postoperative Management Strategies. / Touijer, Karim A.; Karnes, Robert Jeffrey; Passoni, Niccolo; Sjoberg, Daniel D.; Assel, Melissa; Fossati, Nicola; Gandaglia, Giorgio; Eastham, James A.; Scardino, Peter T.; Vickers, Andrew; Cozzarini, Cesare; Montorsi, Francesco; Briganti, Alberto.

In: European Urology, 2017.

Research output: Contribution to journalArticle

Touijer, KA, Karnes, RJ, Passoni, N, Sjoberg, DD, Assel, M, Fossati, N, Gandaglia, G, Eastham, JA, Scardino, PT, Vickers, A, Cozzarini, C, Montorsi, F & Briganti, A 2017, 'Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies', European Urology. https://doi.org/10.1016/j.eururo.2017.09.027
Touijer, Karim A. ; Karnes, Robert Jeffrey ; Passoni, Niccolo ; Sjoberg, Daniel D. ; Assel, Melissa ; Fossati, Nicola ; Gandaglia, Giorgio ; Eastham, James A. ; Scardino, Peter T. ; Vickers, Andrew ; Cozzarini, Cesare ; Montorsi, Francesco ; Briganti, Alberto. / Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy : A Comparative Analysis of Different Postoperative Management Strategies. In: European Urology. 2017.
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title = "Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies",
abstract = "Background: Optimal management of patients with lymph node metastasis (LNM) after radical prostatectomy (RP) remains undefined. Objective: We evaluated the association between three different management strategies and survival in prostate cancer with LNM after RP. Design, setting, and participants: We analyzed data of 1338 patients with LNM after RP from three tertiary care centers. Three hundred and eighty-seven patients (28{\%}) were observed, 676 (49{\%}) received lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23{\%}) received adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty-eight men were followed for more than 10 yr. Outcome measurements and statistical analysis: Primary outcome measure was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier methods were used to visualize OS for the three treatment groups. Cox proportional hazards regression was utilized to compare OS and CSS among the three groups. Results and limitations: ADT + EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95{\%} confidence interval [CI]: 0.32-0.66, p <. 0.0001) or observation (HR: 0.41, 95{\%} CI: 0.27-0.64, p <. 0.0001). Higher-risk patients benefited more from ADT + EBRT than lower-risk patients. Ten-year mortality risk difference between ADT + EBRT, observation, or ADT alone ranged from 5{\%} in low-risk patients to 40{\%} in high-risk patients. Adjuvant ADT + EBRT was also associated with better CSS than observation or ADT alone (p <. 0.0001), ADT had better CSS compared to observation (HR: 0.64, 95{\%} CI: 0.43-0.95, p = 0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95{\%} CI: 1.45-6.40, p = 0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95{\%} CI: 0.65-1.25, p = 0.5). While selection bias might remain, its effect would operate in the opposite direction to our findings. Conclusions: In men with LNM after RP, ADT + EBRT improved survival over either observation or adjuvant ADT alone. This survival benefit increases with higher-risk disease. Patient summary: Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. However, we found that adjuvant androgen deprivation therapy with external beam radiation therapy improved survival in these patients. Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. Adjuvant androgen deprivation therapy with external beam radiation therapy confers a long-term overall survival advantage than either observation or androgen deprivation therapy alone.",
keywords = "Adjuvant radiotherapy, Antineoplastic agents, Hormonal, Lymphatic metastasis, Mortality, Prognosis, Prostatectomy, Prostatic neoplasms",
author = "Touijer, {Karim A.} and Karnes, {Robert Jeffrey} and Niccolo Passoni and Sjoberg, {Daniel D.} and Melissa Assel and Nicola Fossati and Giorgio Gandaglia and Eastham, {James A.} and Scardino, {Peter T.} and Andrew Vickers and Cesare Cozzarini and Francesco Montorsi and Alberto Briganti",
year = "2017",
doi = "10.1016/j.eururo.2017.09.027",
language = "English (US)",
journal = "European Urology",
issn = "0302-2838",
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}

TY - JOUR

T1 - Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy

T2 - A Comparative Analysis of Different Postoperative Management Strategies

AU - Touijer, Karim A.

AU - Karnes, Robert Jeffrey

AU - Passoni, Niccolo

AU - Sjoberg, Daniel D.

AU - Assel, Melissa

AU - Fossati, Nicola

AU - Gandaglia, Giorgio

AU - Eastham, James A.

AU - Scardino, Peter T.

AU - Vickers, Andrew

AU - Cozzarini, Cesare

AU - Montorsi, Francesco

AU - Briganti, Alberto

PY - 2017

Y1 - 2017

N2 - Background: Optimal management of patients with lymph node metastasis (LNM) after radical prostatectomy (RP) remains undefined. Objective: We evaluated the association between three different management strategies and survival in prostate cancer with LNM after RP. Design, setting, and participants: We analyzed data of 1338 patients with LNM after RP from three tertiary care centers. Three hundred and eighty-seven patients (28%) were observed, 676 (49%) received lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23%) received adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty-eight men were followed for more than 10 yr. Outcome measurements and statistical analysis: Primary outcome measure was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier methods were used to visualize OS for the three treatment groups. Cox proportional hazards regression was utilized to compare OS and CSS among the three groups. Results and limitations: ADT + EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66, p <. 0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p <. 0.0001). Higher-risk patients benefited more from ADT + EBRT than lower-risk patients. Ten-year mortality risk difference between ADT + EBRT, observation, or ADT alone ranged from 5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT + EBRT was also associated with better CSS than observation or ADT alone (p <. 0.0001), ADT had better CSS compared to observation (HR: 0.64, 95% CI: 0.43-0.95, p = 0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95% CI: 1.45-6.40, p = 0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95% CI: 0.65-1.25, p = 0.5). While selection bias might remain, its effect would operate in the opposite direction to our findings. Conclusions: In men with LNM after RP, ADT + EBRT improved survival over either observation or adjuvant ADT alone. This survival benefit increases with higher-risk disease. Patient summary: Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. However, we found that adjuvant androgen deprivation therapy with external beam radiation therapy improved survival in these patients. Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. Adjuvant androgen deprivation therapy with external beam radiation therapy confers a long-term overall survival advantage than either observation or androgen deprivation therapy alone.

AB - Background: Optimal management of patients with lymph node metastasis (LNM) after radical prostatectomy (RP) remains undefined. Objective: We evaluated the association between three different management strategies and survival in prostate cancer with LNM after RP. Design, setting, and participants: We analyzed data of 1338 patients with LNM after RP from three tertiary care centers. Three hundred and eighty-seven patients (28%) were observed, 676 (49%) received lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23%) received adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty-eight men were followed for more than 10 yr. Outcome measurements and statistical analysis: Primary outcome measure was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier methods were used to visualize OS for the three treatment groups. Cox proportional hazards regression was utilized to compare OS and CSS among the three groups. Results and limitations: ADT + EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66, p <. 0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p <. 0.0001). Higher-risk patients benefited more from ADT + EBRT than lower-risk patients. Ten-year mortality risk difference between ADT + EBRT, observation, or ADT alone ranged from 5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT + EBRT was also associated with better CSS than observation or ADT alone (p <. 0.0001), ADT had better CSS compared to observation (HR: 0.64, 95% CI: 0.43-0.95, p = 0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95% CI: 1.45-6.40, p = 0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95% CI: 0.65-1.25, p = 0.5). While selection bias might remain, its effect would operate in the opposite direction to our findings. Conclusions: In men with LNM after RP, ADT + EBRT improved survival over either observation or adjuvant ADT alone. This survival benefit increases with higher-risk disease. Patient summary: Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. However, we found that adjuvant androgen deprivation therapy with external beam radiation therapy improved survival in these patients. Lymph node metastasis following radical prostatectomy is associated with poor survival outcomes. Adjuvant androgen deprivation therapy with external beam radiation therapy confers a long-term overall survival advantage than either observation or androgen deprivation therapy alone.

KW - Adjuvant radiotherapy

KW - Antineoplastic agents

KW - Hormonal

KW - Lymphatic metastasis

KW - Mortality

KW - Prognosis

KW - Prostatectomy

KW - Prostatic neoplasms

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U2 - 10.1016/j.eururo.2017.09.027

DO - 10.1016/j.eururo.2017.09.027

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