ESMO 2022: Differential Treatment Response with Nodal Metastases in mHSPC and Evaluation of Nodal Burden as a Prognostic Biomarker -Ancillary Studies of the Docetaxel and Abiraterone Acetate and Prednisolone Phase III Trials from STAMPEDE

(UroToday.com) The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Áine Haran discussing ancillary studies of the docetaxel and abiraterone acetate and prednisolone phase III trials from STAMPEDE, specifically differential treatment response with nodal metastases in mHSPC and evaluation of nodal burden as a prognostic biomarker. Better selection of patients for addition of docetaxel in mHSPC is required. Previous work has suggested that increased disease burden correlates with worse outcomes, but nodal metastases have not been considered in metastatic volume definitions in mHSPC.



In this analysis, overall survival (OS) was compared in subgroups of mHSPC patients (node +/- bone and bone-only), randomized 2:1 ADT +/- docetaxel or 1:1 ADT +/- abiraterone acetate and prednisolone. Nodal burden was dichotomized into low (<5 nodes) and high (≥5 nodes) burden. Cox models were stratified by time period and adjusted for N stage, age (<70, ≥70), WHO performance status, NSAID/aspirin use, radiotherapy, bone metastases, and CHAARTED low or high volume.

1,086 patients from ADT +/- docetaxel and 990 patients from ADT +/- abiraterone acetate and prednisolone were studied. CT/MRI scans for 373 ADT +/- docetaxel and 602 ADT +/- abiraterone acetate and prednisolone patients were also centralized and reviewed for nodal metastases:

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Baseline characteristics between those with nodal disease and bone-only disease showed a higher PSA among patients with lymph node disease:

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Significant OS benefit was demonstrated with ADT + abiraterone acetate and prednisolone in both nodal +/- bone (HR 0.65, 95% CI 0.53-0.78) and bone-only metastases groups (HR 0.55, 95% CI 0.41-0.74). The interaction HR was 1.21, 95% CI 0.86-1.72 (p = 0.278):

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Patients with bone-only metastases treated with ADT + docetaxel had a similar survival benefit (HR 0.62, 95% CI 0.46-0.84). Notably, survival benefit was reduced for ADT + docetaxel in the nodal +/- bone metastases group (HR 0.89, 95% CI 0.74-1.07). This difference was statistically significant by test for interaction (HR 1.43, p = 0.046). Higher nodal burden had significantly worse outcomes in both control arms and the intervention arm of ADT +/- abiraterone acetate and prednisolone.

Dr. Haran concluded this presentation by discussing differential treatment response with nodal metastases in mHSPC and evaluation of nodal burden as a prognostic biomarker with the following take-home messages:

  • Increased nodal burden is a negative prognostic biomarker and should be considered in prospective risk/volume definitions to aid risk stratification in selected patients
  • This study also demonstrates for the first time a potential differential response between mHSPC patients with nodal +/-bone metastases versus bone-only metastases for ADT + docetaxel but not for ADT + abiraterone acetate and prednisolone

Presented by: Áine M. Haran, Genito-urinary Cancer Research Group, The University of Manchester, Manchester, UK

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.