Importance of non-regional lymph nodes in assigning risk in primary metastatic prostate cancer

Abstract

Objective: To determine the prognostic relevance of non-regional lymph node (NRLN) metastases presenting synchronously with bone metastases in metastatic prostate cancer (mPCa) for guiding treatment decisions based on oligometastatic definitions.

Patients and methods: Patients diagnosed with mPCa between 2004 and 2013 were identified from the Surveillance, Epidemiology and End Results database and were grouped by metastatic sites into only NRLN, only bone, bone + NRLN and other sites ± bone/NRLN metastases. Multivariate Cox and competing risk regression analyses were performed to compare the risks of all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) associated with bone + NRLN metastases before and after propensity-score matching to patients with only bone metastases. This was complemented with landmark and supplementary analyses.

Results: Of 17 167 patients with mPCa identified, 63.1% presented with only bone metastases, while bone and NRLN metastases co-occurred in 8.9% of the cohort. On multivariate analyses, after adjusting for potential confounders (clinical and sociodemographic), patients with bone + NRLN metastases had a significantly higher risk of ACM (hazard ratio [HR] 1.161, 95% confidence interval [CI] 1.084-1.243; P < 0.001) and PCSM (subdistribution HR 1.149, 95% CI 1.067-1.237; P < 0.001) compared with patients with only bone metastases. Landmark analyses limited to survivors of ≥6 and ≥12 months again showed a significantly increased risk of ACM for patients presenting with bone + NRLN metastases compared with patients with only bone metastases. In a subsequent 1:1 propensity-score-matched cohort of patients with bone + NRLN metastases and only bone metastases, the bone + NRLN group had higher multivariate-adjusted hazard rates for ACM (HR 1.202, 95% CI 1.102-1.311; P < 0.001) and PCSM (subdistribution HR 1.146, 95% CI 1.044-1.259; P = 0.004).

Conclusions: Patients with concomitant NRLN and bone metastases have a higher risk of death, NRLN and bone metastases therefore representing a high-risk feature, when compared with patients with bone metastases alone. The current therapeutic stratification of 'low-' vs 'high-volume' disease does not account for this phenomenon, and patients requiring aggressive combination therapy may not receive maximum therapeutic benefit as a consequence.

Keywords: Surveillance, Epidemiology and End Results; lymph node; metastasis; prostate cancer; staging.