Abstract 634P
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 (HR=1.61, 95%CI 1.12–2.31, p=0.013; 5yr KM estimated OS 27% for ≥5 NRLN vs 40% for <5NRLN) and ADT + docetaxel group (HR=1.79, 95%CI 1.10–2.92, p=0.024; 5yr OS 35% vs 53%). FFS was also worse for patients with ≥5 nodes in the ADT group (HR=1.51, 95%CI 1.07–2.14, p=0.024) and the ADT + docetaxel group (HR=1.78, 95%CI 1.12–2.81, p=0.018).
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.
Clinical trial identification
NCT00268476; ISRCTN78818544.
Editorial acknowledgement
Legal entity responsible for the study
University of Manchester and the Medical Research Council Clinical Trials Unit (MRC CTU), University College London.
Funding
Has not received any funding.
Disclosure
G. Attard: Advisory/Consultancy, Personal fees & non-financial support outside the submitted work: Sanofi Aventis; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Astellas; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Medivation; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Abbott Laboratories; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Essa Pharmaceuticals; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Bayer Healthcare Pharmaceuticals; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Janssen; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Roche/Ventana; Non-remunerated activity/ies, Personal fees & non-financial support outside the submitted work: Pfizer; Advisory/Consultancy, Personal fees: Novartis; Advisory/Consultancy, Personal fees: Millennium Pharmaceuticals; Advisory/Consultancy, Personal fees: Takeda; Advisory/Consultancy, Personal fees: Veridex; Advisory/Consultancy, Personal fees and share of royalty income from abiraterone : Institute of Cancer Research (ICR); Research grant/Funding (self), Grants outside of the submitted work: AstraZeneca; Research grant/Funding (self), Grants outside of the submitted work: Arno Therapeutics; Research grant/Funding (self), Grants outside of the submitted work: Innocrin Pharma; Research grant/Funding (self), Grants outside of the submitted work: Veridex. H. Douis: Research grant/Funding (self), Grant during the conduct of the study: Janssen. M.K. Parmar: Research grant/Funding (institution), Non-remunerated activity/ies: Astellas; Research grant/Funding (self), Non-remunerated activity/ies: Clovis Oncology; Research grant/Funding (self), Non-remunerated activity/ies: Novartis; Research grant/Funding (self), Non-remunerated activity/ies: Pfizer; Research grant/Funding (institution), Non-remunerated activity/ies: Sanofi. M.R. Sydes: Non-remunerated activity/ies, Grants and non-financial support outside the submitted work: Astellas; Non-remunerated activity/ies, Grants and non-financial support outside the submitted work: Clovis Oncology; Non-remunerated activity/ies, Grants and non-financial support outside the submitted work: Novartis; Non-remunerated activity/ies, Grants and non-financial support outside the submitted work: Pfizer; Non-remunerated activity/ies, Grants, personal fees and non-financial support outside the submitted work: Janssen; Advisory/Consultancy, Personal fees outside the submitted work: Eli Lilly. N.D. James: Leadership role, other: Sanofi; Leadership role, other: Novartis; Advisory/Consultancy, Non-remunerated activity/ies, grants, personal fees and non-financial support: Janssen. N.W. Clarke: Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: Sanofi Aventis; Advisory/Consultancy, Received fees for consultation and lectureships during this study and outside of submitted work : Janssen; Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: Astellas; Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: Pfizer; Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: AstraZeneca; Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: Bayer; Advisory/Consultancy, Received fees for consultation and lectureships outside the submitted work: Ferring Pharmaceuticals. All other authors have declared no conflicts of interest.