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

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), determine whether M1b/M1c is the most appropriate M-stage and evaluate the additional importance to the distinction in low/high volume disease.

All men diagnosed with synchronous mHSPC from 2010-2018 in the Netherlands were identified in the Netherlands Cancer Registry (NCR). Men were categorized 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 (>5.600 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 (HR).

Compared to men with NRLN and bone metastases (reference group), OS of men with only NRLN (HR:0.70, 95%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%CI:0.58-0.98), but not in the high volume subgroup (0.99, 95%CI:0.84-1.18). In contrast, 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).

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 TNM classification should be contemplated. Furthermore, definitions of metastatic burden need to be re-evaluated.

BJU international. 2021 Nov 06 [Epub ahead of print]

Berdine L Heesterman, Henk G van der Poel, Ivo G Schoots, Niven Mehra, Katja K H Aben

Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.