Development and validation of a novel risk model in newly diagnosed de novo bone metastatic prostate cancer (M1b): a retrospective study

Abstract

Background Previous studies suggested that bone metastasis has a significant effect on the time of progression to metastatic castration-resistant prostate cancer (CRPC) for newly diagnosed de novo bone metastatic hormone-sensitive prostate cancer (mHSPC). Nevertheless, the effect of different bone metastasis sites was not fully evaluated. This study aimed to develop and validate a novel bone metastatic risk model. Methods We enrolled 122 patients who were newly diagnosed with de novo bone metastatic prostate cancer following primary androgen deprivation based therapy at our institution from January 2008 to June 2021. The metastatic bone sites were classified into six sites: skull; cervical, thoracic, and lumbar vertebrae; chest (ribs and sternum); pelvis; upper limbs; and lower limbs. We calculated the bone metastatic score (BMS) for each site: 0 points were assigned for non-metastasis and 1 point was assigned for metastasis. The X-tile was adopted to acquire optimal cutoff points of BMS. We defined high-risk group (HRG) as BMS ≥ 3 and low-risk group (LRG) as BMS < 3. The new bone risk stratification was validated by calculating the area under the receiver operating characteristic curve (AUC). Subsequently, the relevant clinical prognostic variables were added to construct a predictive nomogram for predicting CRPC. Results The median patient age was 73 years. Most patients had Gleason score ≤8 (93 cases, 76.2%). The median follow-up duration was 11.5 months (range: 2–92 months). Eighty-six patients progressed to CRPC during the follow-up. The most common bone metastatic site was the pelvis (90.2%). The median BMS was 4. Seventy-six patients had HRG, while forty-six had LRG. The 1-, 2-, and 3-year AUCs for H/LRG were 0.620, 0.754, and 0.793, respectively. The HRG was associated with earlier time to CRPC. A nomogram based on four parameters (Gleason score, H/LRG, prostate-specific antigen [PSA] nadir, and time to PSA nadir) was developed to predict CRPC. Internal validation using bootstrapping demonstrated good accuracy for predicting the CRPC (C-index: 0.727). The calibration analysis demonstrated that the model performed well. Conclusion We established a novel H/LRG risk model for newly diagnosed de novo bone metastatic prostate cancer, which provided evidence to support clinical decision-making.