Which Patients with Clinically Node-positive Prostate Cancer Should Be Considered for Radical Prostatectomy as Part of Multimodal Treatment? The Impact of Nodal Burden on Long-term Outcomes

Abstract

Background: A role for local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies has been proposed. However, no data are available to identify men who would benefit from RP in this setting.

Objective: To identify predictors of clinical recurrence (CR) in surgically managed PCa patients with clinical lymphadenopathies.

Design, setting, and participants: We identified 162 patients with lymphadenopathies treated with RP and lymph node dissection at three referral centers.

Outcome measures and statistical analyses: CR was defined as the onset of metastases detected by conventional imaging. Kaplan-Maier analyses assessed time to CR after stratifying patients according to the site of lymphadenopathies and nodal burden. Regression tree analysis stratified patients into risk groups on the basis of their preoperative characteristics.

Results and limitations: Overall, 80% of patients had lymphadenopathies in the pelvis alone and 20% in the retroperitoneum±pelvis. The median size of positive nodes was 13mm. A total of 84 patients (52%) received neoadjuvant androgen deprivation therapy and 127 (78%) had pathological lymph node invasion. The median follow-up for survivors was 64 mo. The 8-yr CR-free and CSM-free survival rates were 59% and 80%, respectively. Biopsy grade group and preoperative nodal burden should identify patients more likely to experience CR. While <10% of men with biopsy grade group 1-3 and two or fewer clinical lymphadenopathies developed CR, up to 60% of patients with biopsy grade group 4-5 and retroperitoneal node involvement ultimately experienced CR at 8 yr after RP. The discrimination of the regression tree was 76% according to the area under the receiver operating characteristic curve. Our study is limited by potential unmeasured confounders and the relatively small sample size.

Conclusions: Surgery in a multimodal setting might play a role in PCa patients with biopsy grade group 1-3 and/or enlarged nodes in the pelvis. Conversely, grade group 4-5 PCa and lymphadenopathies in the retroperitoneum are associated with worse oncologic outcomes.

Patient summary: Approximately half of prostate cancer patients with clinical lymphadenopathies treated with radical prostatectomy are free from metastases at 8-yr follow-up. Radical prostatectomy with or without systemic therapies might play a role in selected patients with biopsy grade group 1-3 disease and/or enlarged nodes in the pelvis. Conversely, a higher grade group and the presence of lymphadenopathies in the retroperitoneum should identify candidates for systemic therapies upfront.

Keywords: Lymph node dissection; Nodal metastases; Node-positive disease; Prostate cancer; Radical prostatectomy.