Association of dynamic changes in serological markers with survival in de novo metastatic hormone-sensitive prostate cancer.
Authors: Roy Soumyajit , Le Amy Trinh , Spratt Daniel Eidelberg , Sun Yilun , Morgan Scott C. , Marwaha Gaurav , Kishan Amar Upadhyaya , Wallis Christopher J.D. , Saad Fred , Malone Shawn 
Published: June 2023

5069 Background: Prognostic association of serological markers of systemic inflammatory response have been demonstrated in metastatic castrate resistant prostate cancer. However, it remains unknown whether dynamic changes in these markers over time are prognostic earlier in the disease process, namely in metastatic hormone sensitive prostate cancer (mHSPC). We performed a secondary analysis of LATITUDE trial to determine if dynamic changes in hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) are predictive of prostate cancer-specific survival (PCSS), and overall survival (OS). Methods: We used a joint model approach to determine the association of the dynamic change in the marker levels with PCSS, and OS. For the time-to-event submodel, a multivariable Cox regression model was constructed with treatment arm, skeletal lesion number, liver or lung metastasis, ECOG performance status, and age. For the longitudinal submodel, a linear mixed-effects model was built with an interaction term for treatment arm and time of evaluation in addition to treatment arm, time of evaluation, and baseline value of the serological markers. The two submodels were linked through a shared random effect. Results: Overall 1172 patients were eligible - 580 from the abiraterone plus ADT arm and 592 from the ADT alone group. Median follow-up for surviving patients was 52 months (IQR 47-57). Median number of post-baseline assessments was 16 (IQR 10-28). On univariate joint models, every 10 g/L dynamic increase in Hb was associated with superior PCSS (HR 0.71 [0.67-0.75]) and OS (HR 0.74 [0.68-0.79]) while every 5 points dynamic increase in LMR was associated with a superior PCSS (HR 0.38 [0.26-0.53]) and OS (HR 0.41 [0.29-0.56]). In contrast, dynamic increase in NLR was associated with inferior PCSS (HR 1.29 [1.22-1.36]) and OS (HR 1.29 [1.23-1.36]) while every 10-point dynamic increase in PLR was associated with a small but significant deterioration in PCSS (HR 1.05 [1.04-1.06]) and OS (HR 1.05 [1.04-1.06]), respectively. On multivariate joint modeling, dynamic increase in Hb was also associated with superior PCSS (HR per 10g/L increase 0.74 [0.69-0.79]) and OS (HR per 10g/L rise 0.75 [0.71-0.80]). When dynamic changes in Hb, LMR, NLR, and PLR were included in the same multivariate model with dynamic change in PSA, dynamic increase in Hb continued to show association with significantly superior PCSS (HR per 10g/L rise 0.80 [0.75-0.86]), and OS (HR per 10g/L rise 0.81 [0.75-0.86]), respectively. Conclusions: Our findings suggest that dynamic increase in hemoglobin can predict for superior PCSS, and OS in men with de novo mHSPC treated with ADT with or without abiraterone. These findings need additional validation before implementing routine use of hemoglobin as a prognostic biomarker in de novo mHSPC.