Background Metastatic castration-sensitive prostate cancer (mCSPC) is a heterogeneous disease with variable clinical outcomes despite advances in androgen receptor signaling inhibitor (ARSI)-based therapy. We aimed to develop and externally validate a prognostic model for predicting progression to castration-resistant prostate cancer (CRPC) in patients with mCSPC. Methods This multicenter retrospective study included patients with mCSPC treated with ARSI doublet therapy. The development cohort comprised 388 patients, whereas the external validation cohort included 451 patients. Prognostic factors for CRPC-free survival (CRPC-FS) were identified using Cox proportional hazards regression models. A point-based risk score (JIKEI-YAYOI score) was derived from regression coefficients. Model performance was evaluated through assessment of discrimination, calibration, and external validation. Results In the development cohort, the median CRPC-FS was 21 months. Grade Group, extent of disease score, hemoglobin, and lactate dehydrogenase were independently associated with CRPC progression and were incorporated into the model. The model demonstrated good discrimination (apparent C-index, 0.715; optimism-corrected C-index, 0.720). The JIKEI-YAYOI score ranged from 0 to 8, corresponding to a 3-year CRPC risk of 10.6%-93.2%. Patients were stratified into low-risk (<= 2), intermediate-risk (3-4), and high-risk (>= 5) groups, with significantly different CRPC-FS and overall survival (both p < 0.001). External validation confirmed good discrimination, calibration, and risk stratification. Conclusions The JIKEI-YAYOI score is a simple, clinically applicable tool for predicting progression to CRPC in patients with mCSPC. Using routinely available clinical variables, it enables individualized risk assessment and may support clinical decision-making regarding surveillance and treatment strategies.
Objectives Perioperative treatment with enfortumab vedotin (EV) plus pembrolizumab has demonstrated a high pathological complete response (pCR) rate in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). However, whether this therapeutic benefit reflects true pharmacologic synergy or can be explained by independent drug action (IDA) remains uncertain.Methods We analyzed data from EV-103 cohort H (EV monotherapy), the cisplatin-ineligible subset of PURE-01 (pembrolizumab monotherapy), and KEYNOTE-905/EV-303 (EV plus pembrolizumab). An IDA model incorporating a Gaussian copula was applied to estimate the predicted pCR rate of the combination therapy. The primary analysis assumed weak positive dependence between drug responses (correlation coefficient rho = 0.24). Sensitivity analyses evaluated the observed-minus-IDA-predicted pCR difference across a continuous range of dependence assumptions (rho = 0.00-0.99).Results The predicted pCR rate for EV plus pembrolizumab was 53.5%, consisting of 21.4% EV-only responders, 17.1% pembrolizumab-only responders, and 15.0% dual responders. The observed pCR rate in the KEYNOTE-905/EV-303 trial was 57.1%, corresponding to an absolute difference of 3.6 percentage points compared with the model prediction. In sensitivity analyses, the posterior median observed-minus-predicted difference increased with stronger positive dependence, but the 95% credible intervals were wide and included zero across a broad range of dependence assumptions.Conclusions Although modest pharmacologic synergy cannot be excluded given the uncertainty in the available data, substantial population-level pharmacologic synergy is not required to explain the high pCR observed with the combination.
Objectives Lower urinary tract symptoms (LUTS) are common in men and have been linked to mental health, but their relationship with depressive symptoms across the adult age range, including young men, remains unclear. We examined the association between LUTS and depressive symptoms in Japanese men. Methods Using an internet research panel, 4000 never-smoking Japanese men were surveyed. LUTS were assessed with the Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), International Prostate Symptom Score (IPSS), and Quality of Life (QOL) index, and depressive symptoms with the Quick Inventory of Depressive Symptomatology, Japanese version (QIDS-J). Scores were compared across QIDS-J severity groups, and multivariable regression was used to adjust for age and household income. Results Of 2568 respondents (mean age 46.6 years), more severe depressive symptoms were associated with younger age (p < 0.001). ICIQ-SF and IPSS increased with QIDS-J severity (both p < 0.001) and remained independently associated after adjustment for age and income (IPSS adjusted beta 0.32; ICIQ-SF 0.13; both p < 0.001), whereas OABSS was not associated (p = 0.193). The same pattern was observed in men aged 20-40 years. Conclusions Greater depressive symptom severity was independently associated with higher IPSS and ICIQ-SF scores, but not with OABSS, OAB, or UUI among Japanese male never-smokers.
ABSTRACT Objectives To evaluate whether a separate preoperative prostate biopsy can be deferred using magnetic resonance imaging (MRI) and prostate‐specific antigen density (PSAD) in candidates for holmium laser enucleation of the prostate (HoLEP). Methods We retrospectively analyzed 625 patients who underwent HoLEP. In the high prostate‐specific antigen (PSA) cohort (≥ 4.0 ng/mL, n = 455), the diagnostic performance of PSAD was evaluated. In patients without a prior biopsy within 1 year who underwent preoperative MRI ( n = 126), candidates for biopsy deferral (MRI‐negative and PSAD < 0.20 ng/mL/mL, n = 95) were assessed. Clinically significant prostate cancer (csPCa) detection rates and histologically validated negative predictive values (NPVs) were determined using simultaneous peripheral zone (PZ) biopsy. Results Multivariable analysis identified PSAD ≥ 0.20 ng/mL/mL as an independent predictor of csPCa (odds ratio: 3.80, 95% confidence interval [CI]: 1.35–10.64, p = 0.011). In patients without a prior biopsy within 1 year ( n = 343), PSAD < 0.20 ng/mL/mL achieved a specificity of 85.9% and a biopsy deferral rate of 84.8%. Among 126 MRI‐evaluated patients, the combined criteria (MRI‐negative and PSAD < 0.20 ng/mL/mL) yielded a sensitivity of 83.3%, specificity of 78.3%, an NPV of 98.9% (94/95), and a biopsy deferral rate of 75.4% (95/126). The histologically validated NPV obtained via simultaneous PZ biopsy ( n = 77) was 98.7% (76/77). Conclusions Combining negative MRI and PSAD < 0.20 ng/mL/mL demonstrated a high NPV for csPCa and may allow the deferral of separate preoperative biopsies in selected patients with large‐volume benign prostatic hyperplasia (BPH).
