(UroToday.com) The 2022 ASCO annual meeting featured a session on prostate cancer, including a presentation by Dr. Lucky Lara discussing data from the SWOG S1216 trial of ADT +/- orteronel assessing bone biomarkers and overall survival in men with advanced HSPC. Skeletal metastasis is common in men with advanced prostate cancer and is a frequent source of morbidity, and the homeostatic balance between bone formation and resorption is disrupted in these men. This disruption is clinically assessable with bone metabolism in the serum. Circulating bone biomarkers are strongly prognostic for OS in castration-resistant prostate cancer (CRPC). Dr. Lara and colleagues prospectively evaluated bone biomarkers in men with HSPC in S1216, a trial that established new OS benchmarks. They sought to identify patient subsets with differential OS outcomes as defined by bone biomarkers.
Markers of bone resorption [CTx; PYD] and formation [CICP; BAP] were assessed. Patients were randomly divided into training (1/3; n = 316) and validation (2/3; n = 633) sets. In the training set, recursive partitioning of OS was used to identify the ideal dichotomous cutpoint for each bone biomarkers and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazard models were used to assess impact of bone biomarkers on OS, adjusted for patient and tumor characteristics. Adjusted odds ratios for 3-year OS based on bone biomarkers and baseline clinical factors were developed using logistic regression to estimate receiver operating characteristic (ROC) curves.
Among 1,279 men, 949 had baseline bone biomarkers. The median age was 68 years, the median PSA was 28 ng/dL, 60% of patients had Gleason > 7 disease, and 97% of men had Zubrod PS 0/1. Values of bone biomarkers at the median and at cutpoints maximized for OS were identified. For 3 of the bone biomarkers, the cutpoint was at the 85th percentile, and for PYD it was at the median. Recursive partitioning algorithms applied to the training set identified 4 groups with differential OS based on a dichotomous split of CTx in combination with additional CICP splits within each group. Hazard ratios (HR) for OS based on elevated bone biomarkers are as follows:
ROC analysis showed that only BAP & PYD had significantly higher AUC (0.73; 0.74) compared to AUC of baseline clinical factors (0.71) (p = 0.02 and 0.03 respectively). There was no evidence of bone biomarkers x treatment interaction (all p >= 0.2). The Kaplan Meier curves for bone marker combination in the validation set is as follows:
Dr. Lara concluded this presentation discussing data from the cc assessing bone biomarkers and overall survival in men with advanced HSPC with the following concluding points:
- In men initiating ADT for HSPC, elevated bone biomarkers are strongly prognostic for worse OS
- Bone biomarkers levels alone and in combination with patient/tumor characteristics identify unique subsets of men with high probability of being alive at 3 years from ADT initiation
- These results validate the clinical value of bone biomarkers in the HSPC state, extending bone biomarkers utility beyond CRPC
Presented by: Primo "Lucky" N. Lara, MD, University of California, Sacramento, CA,
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 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.