Impact of metastatic lymph node burden on survival in patients with mHSPC from the 'docetaxel comparison' of the STAMPEDE trial

Abstract

Background: Increasing metastatic burden is associated with worsening prognosis. However, none of the current burden definitions consider metastatic lymph node volume, number and distribution. In this exploratory analysis of cross-sectional baseline staging scans from the STAMPEDE "docetaxel comparison” we evaluate metastatic lymph node burden as a prognostic factor. Methods: 629 patients with metastatic disease randomised between 2005 and 2013 to Arm A (androgen deprivation therapy (ADT)) or Arm C (ADT + docetaxel) with available baseline scans were analysed. Lymph node analysis was done using the UK Royal College of Radiologists diagnostic criteria with central review of CT/MRI scans performed jointly by a radiologist and urologist. Annotation of lymph node number and size was completed for both regional and non-regional sites. Overall survival (OS) and failure-free survival (FFS) were used as endpoints. Hazard ratios were obtained separately for each treatment group using multivariable Cox regression analysis adjusted for age (<70 or 70), WHO PS (0 or 1-2), nodal status (N0, N1 or NX), NSAID or aspirin use (uses either or no), Gleason score ( 7, 8-10 or unknown), bone metastases counts (<5 or 5) and concomitant metastatic site (only metastatic lymph nodes, bone (+/-NRLN) or any visceral (+/-bone)). Results: 178/629 (29%) patients had nodal metastases with a median maximum diameter of 2.1 (range 1.0 to 8.1) cm and median minimum diameter of 1.2 (range 0.9 to 3.9) cm. 87/629 (14%) patients had 5 or more nodes. Patients with 5 metastatic nodes had worse OS compared to patients with <5 nodes in both the ADT group (HR¼1.61, 95%CI 1.12e2.31, p¼0.013; 5yr KM estimated OS 27% for 5 NRLN vs 40% for <5NRLN) and ADT + docetaxel group (HR¼1.79, 95%CI 1.10e2.92, p¼0.024; 5yr OS 35% vs 53%). FFS was also worse for patients with 5 nodes in the ADT group (HR¼1.51, 95%CI 1.07e2.14, p¼0.024) and the ADT + docetaxel group (HR¼1.78, 95%CI 1.12e2.81, p¼0.018). Conclusions: Increased metastatic burden of 5 or more nodal metastases is an independent prognostic factor for poorer outcomes in patients with mHSPC treated with ADT or ADT + docetaxel and should be considered for inclusion along with bone metastases counts in future metastatic burden definitions.