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.

Keywords: Adjuvant radiotherapy; Antineoplastic agents; Hormonal; Lymphatic metastasis; Mortality; Prognosis; Prostatectomy; Prostatic neoplasms.

Fig. 1. (A) Kaplan-Meier curve for overall survival and (B) cancer-specific survival stratified by treatment group

Black line is androgen deprivation therapy plus external beam radiation therapy, blue line is ADT, and red line is observation. Black line is androgen deprivation therapy plus external beam radiation therapy, blue line is androgen deprivation therapy, and red line is observation. ADT = androgen deprivation therapy; EBRT = external beam radiation therapy; RP = radical prostatectomy

Fig. 1. (A) Kaplan-Meier curve for overall survival and (B) cancer-specific survival stratified by treatment group

Black line is androgen deprivation therapy plus external beam radiation therapy, blue line is ADT, and red line is observation. Black line is androgen deprivation therapy plus external beam radiation therapy, blue line is androgen deprivation therapy, and red line is observation. ADT = androgen deprivation therapy; EBRT = external beam radiation therapy; RP = radical prostatectomy

Fig. 2. Observed versus the predicted risk of death among patients receiving ADT+EBRT

Black line is the difference in risk of all-cause mortality after radical prostatectomy by treatment among men with lymph node metastasis with and without adjuvant androgen deprivation therapy plus external beam radiation therapy. The grey dashed lines are the 95% confidence intervals. Positive differences suggest a survival benefit for patients receiving androgen deprivation therapy + external beam radiation therapy. A dotted grey line has been added at zero, for reference. ADT = androgen deprivation therapy; EBRT = external beam radiation therapy; RT = radiation therapy.