Background/Objectives: Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used. Results: Overall, 35% progressed to mCRPC biochemically vs. 23% radiographically vs. 42% biochemically + radiographically. The PSA nadir in mHSPC (1.4 vs. 0.4 vs. 0.8 ng/mL) and PSA level at mCRPC progression (15 vs. 2 vs. 21 ng/mL, both p ≤ 0.01) were significantly higher for biochemical vs. radiographic vs. both progressed patients. In PFS and OS analyses, no significant differences were observed among all three compared groups. In the comparison of the staging used for progression to mCRPC, 67% received conventional vs. 33% PSMA-PET/CT, with higher metastatic burden in mHSPC and osseous lesions in mCRPC for conventionally staged patients (both p < 0.01). In PFS (15.3 vs. 10.1 months, hazard ratio [HR]: 0.75) and OS analyses (52.6 vs. 34.3 months, HR: 0.61, both p < 0.05), PSMA-PET/CT harbored better prognosis; however, this did not hold after multivariable adjustment. Similar results were observed for further analyses in second- and third-line mCRPC or patients with a PSA level of ≥2 ng/mL. Conclusions: The cause of progression to mCRPC seems not to influence cancer-control outcomes, despite important baseline tumor characteristic differences. The PSMA-PET/CT staging modality might be associated with better PFS and OS outcomes, possibly due to its more sensitive detection of progression or new metastatic lesions.

Background: A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the reduced risk of severe urinary tract infections. However, its impact on the detection of clinically significant prostate cancer (csPCa) remains unclear. Materials and methods: We relied on a prospectively maintained tertiary care database to identify patients who underwent either TP or TR prostate biopsy between 01/2014 and 12/2023. Of those, only patients with suspicious magnetic resonance imaging (MRI) PIRADS lesions (Likert-scale: 3,4,5) received MRI-targeted and systematic biopsies. Detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥ 2) were compared between biopsy approach (TP vs. TR) according to index lesion. Subsequently, uni- and multivariable logistic regression models were applied to investigate the predictive status of the biopsy approach within each subcohort. Results: Of 2063 patients, 1118 (54%) underwent combined MRI-guided and systematic prostate biopsy and were included in the final cohort. Of those, 127 (11%) and 991 (89%) underwent TP vs. TR. CsPCa rates, regardless of differences in patients’ demographics and distribution of index PIRDAS lesions, did not differ statistically significantly and were 51 vs. 52%, respectively (p = 0.8). CsPCa detection rates for PIRDAS-3, PIRADS-4 and PIRADS-5 did not differ and were 24 vs. 23%, 48 vs. 51% and 72 vs. 76% for PIRADS-3, PIRADS-4 and PIRADS-5 subgroups for TP vs. TR, respectively (all p ≥ 0.9) Conclusions: The current results support the available data indicating that TP biopsy approach is comparable to transrectal biopsy approach regarding csPCa detection rates.

Hormonal agents administered for metastatic castration-resistant prostate cancer may lead to osteoporosis, skeletal events, reduced quality of life and even reduced overall survival. Bone-modifying agents may prevent from those events but their effect on cancer-control outcomes remain uncertain. Relying on our institutional tertiary-care database to explore the effect of bone-modifying agents (bisphosphonates such as zoledronic acid and denosumab) on OS and progression-free survival in metastatic castration-resistant prostate cancer patients with at least one bone metastasis in Kaplan-Meyer estimates and Cox regression models. Of 420 metastatic castration-resistant prostate cancer patients, 60% received bone-modifying agents, which were younger (68 vs. 69 years) with more systemic treatment lines for mCRPC (3 vs. 2) and higher proportion of initial DeNovo metastatic disease (72% vs. 62%, all P≤.04) than patients without bone-modifying agents. In progression-free survival analyses, no significant differences were observed between both groups. In overall survival analyses, significant median overall survival differences were observed in favor of patients with bone-modifying agents (58 vs. 45 months, hazard ratio [HR]: 0.66), even after multivariable adjustment (HR: 0.37, both P≤.01). In bone-modifying agent-stratified analyses, 57% received denosumab vs. 43% bisphosphonates, with a significant higher rate of Eastern Cooperative Oncology Group status ≥2 patients in the bisphosphonates group. In progression-free and overall survival analyses, no significant differences were observed between bisphosphonates vs. denosumab patients, with numeric better results in progression-free survival analysis for denosumab after adjusting for covariates. Cumulative rate of osteonecrosis of the jaw at any treatment time was 12% in both groups and significantly decreased over time. Real-world data suggest a relatively low administration rate of bone-modifying agents in osseous metastatic castration-resistant prostate cancer patients. However, real-world also suggest an overall survival benefit, when bone-modifying agents are used, even after controlling for possible confounding patient and tumor characteristics. The use of bone-modifying agents is associated with better cancer-control outcomes in metastatic castration-resistant prostate cancer patients. However, differences between the two types of anti-resorptive treatments, bisphosphonates and denosumab, were not seen. Importantly, rates of patients receiving bone-modifying agents are relatively low and clinicians should aim to improve those rates.