Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy

TY - JOUR

T1 - Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy

AU - Bravi, Carlo A

AU - Droghetti, Matteo

AU - Fossati, Nicola

AU - Gandaglia, Giorgio

AU - Suardi, Nazareno

AU - Mazzone, Elio

AU - Cucchiara, Vito

AU - Scuderi, Simone

AU - Barletta, Francesco

AU - Schiavina, Riccardo

AU - Osmonov, Daniar

AU - Juenemann, Klaus-Peter

AU - Boeri, Luca

AU - Karnes, R Jeffrey

AU - Kretschmer, Alexander

AU - Buchner, Alexander

AU - Stief, Christian

AU - Hiester, Andreas

AU - Nini, Alessandro

AU - Albers, Peter

AU - Devos, Gaëtan

AU - Joniau, Steven

AU - Van Poppel, Hendrik

AU - Grubmüller, Bernhard

AU - Shariat, Shahrokh F

AU - Heidenreich, Axel

AU - Pfister, David

AU - Tilki, Derya

AU - Graefen, Markus

AU - Gill, Inderbir S

AU - Mottrie, Alexandre

AU - Karakiewicz, Pierre I

AU - Montorsi, Francesco

AU - Briganti, Alberto

N1 - Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2022/6

Y1 - 2022/6

N2 - BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

AB - BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

U2 - 10.1016/j.euo.2021.06.003

DO - 10.1016/j.euo.2021.06.003

M3 - SCORING: Journal article

C2 - 34176768

VL - 5

SP - 285

EP - 295

JO - EUR UROL ONCOL

JF - EUR UROL ONCOL

SN - 2588-9311

IS - 3

ER -