Prognostic importance of concomitant non-regional lymph node and bone metastases in men with newly diagnosed metastatic prostate cancer

Objectives: To evaluate the prognostic importance of concomitant non-regional lymph node (NRLN) and bone metastases in men with synchronous metastatic hormone-sensitive prostate cancer (mHSPC), and to determine whether M1b/M1c is the most appropriate M-stage and evaluate the additional importance to the distinction in low/high volume disease. Patients and Methods: All men diagnosed with synchronous mHSPC from 2010 to 2018 in the Netherlands were identified in the Netherlands Cancer Registry. Men were categorised as having NRLN (M1a), bone (M1b), NRLN and bone (M1c), or visceral metastases (M1c). For men diagnosed since October 2015 disease volume could be determined. Analyses were performed in this cohort (>5600 men) and repeated in the 2010–2018 cohort (>14 000 men). The primary outcome measure in this observational cohort study was overall survival (OS) and Cox regression was used to calculate hazard ratios (HRs). Results: Compared to men with NRLN and bone metastases (reference group), OS of men with only NRLN (HR 0.70, 95% confidence interval [CI] 0.55–0.88) was better. This was also true for men with only bone metastases in the low-volume subgroup (HR 0.75, 95% CI0.58–0.98), but not in the high-volume subgroup (HR 0.99, 95% CI 0.84–1.18). In contrast, the OS of men with visceral metastases was worse (HR 2.20, 95% CI 1.75–2.77 + 0.97/month, 95% CI 0.96–0.98). Conclusion: In men with low-volume synchronous mHSPC, presence of concomitant NRLN and bone metastases (currently classified as M1c), is a poor prognostic sign. However, survival of men with visceral metastases (M1c) is worse. Implying that classifying concomitant NRLN and bone metastases as M1c or M1b is not appropriate. Adding a fourth M1-category to the ninth edition of the Tumour-Node-Metastasis classification should be contemplated. Furthermore, definitions of metastatic burden need to be re-evaluated.