Better selection of patients (pts) for addition of docetaxel in mHSPC is required. Increased disease burden correlates with worse outcomes but nodal metastases have not been considered in metastatic volume definitions in mHSPC.
Overall survival (OS) was compared in subgroups of mHSPC pts (node +/- bone and bone-only), randomized 2:1 ADT +/- docetaxel or 1:1 ADT +/- AAP. 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 PS, NSAID/aspirin use, radiotherapy (RT), bone metastases and CHAARTED low or high volume.
1086 pts from ADT +/- docetaxel and 990 pts from ADT +/- AAP were studied. CT/MRI scans for 373 ADT +/- docetaxel and 602 ADT +/- AAP pts were also centralized and reviewed for nodal metastases. Significant OS benefit was demonstrated with ADT + AAP in both nodal +/- bone and bone-only metastases groups. Pts with bone-only metastases treated with ADT + docetaxel had a similar survival benefit. Notably, survival benefit was reduced for ADT + docetaxel in the nodal +/- bone metastases group. This difference was statistically significant by test for interaction (interaction HR 1.43, p=0.046). Higher nodal burden had significantly worse outcomes in both control arms and the research arm of ADT +/- AAP. Table: 1359MO
|ADT/docetaxel HR (95% CI), p||ADT/AAP HR (95% CI), p|
|Nodal +/-bone metastases||0.89 (0.74-1.07), 0.225||0.65 (0.53-0.78), <0.001|
|Bone only metastases||0.62 (0.46-0.84), 0.002||0.55 (0.41-0.74), <0.001|
|Prognostic evaluation of nodal burden|
|Control arm||1.67 (1.13-2.48), 0.011||1.45 (1.07-1.96), 0.016|
|Research arm||1.58 (0.94-2.67), 0.083||1.42 (1.02-1.98), 0.04|
Increased nodal burden is a negative prognostic biomarker and should be considered in prospective risk/volume definitions to aid risk stratification in selected patients. We also demonstrate for the first time a potential differential response between mHSPC pts with nodal +/-bone metastases versus bone-only metastases for ADT + docetaxel but not for ADT + AAP.
Clinical trial identification
Legal entity responsible for the study
The Christie NHS Foundation Trust and the Medical Research Council Clinical Trials Unit at University College London.
Surgical Research Fund at The Christie NHS Foundation Trust.
All authors have declared no conflicts of interest.