Real-world retrospective study of prostate-specific antigen and safety assessment with darolutamide plus androgen deprivation therapy for metastasis hormone-sensitive prostate cancer.

Background: ARASENS has demonstrated the efficacy and safety for darolutamide (DARO) with androgen deprivation therapy (ADT) plus docetaxel in metastasis hormone-sensitive prostate cancer (mHSPC). There is a lack of reports for DARO with ADT in mHSPC though the regimen is used in clinical from time to time. Moreover, recent studies have supported the importance of early and rapid prostate-specific antigen (PSA) reduction, which correlates with reduced disease progression and improved survival in patients with mHSPC. This study aims to evaluate PSA reduction as a primary endpoint for DARO with ADT in the treatment of mHSPC and to evaluate the real-world short-term PSA control of DARO with ADT from two leading medical centers in China. Methods: We retrospectively reviewed the clinical records of patients with mHSPC receiving ADT and DARO (600 mg, b.i.d.). The collection of data spanned from March 1, 2022, to July 31, 2023. The main observation indicators were PSA level and drug-related adverse events (AE) after medication. PSA levels were closely monitored prior to treatment initiation and at 2-week intervals, as well as at 1, 3, and 6 months after the initiation of treatment. We also conducted an analysis to determine the proportion of patients achieving a PSA reduction of 50% or more (PSA50) and 90% or more (PSA90) as well as the percentage of patients with a notable decrease in PSA level to 0.2 ng/mL and PSA nadir of ≤0.02 ng/mL. Results: Fifty-one patients were included in the study, with a median age of 73 years. At diagnosis of HSPC, the majority of patients had a Gleason score ≥8 (n=40, 78.40%) and a median baseline PSA level of 88 ng/mL. Approximately 45.1% (n=23) of patients had a Charlson Comorbidity Index over 1 and were receiving one or more nontumor-related treatments. The median follow-up time was 9.3 months (range, 1.16-15.8 months). The median reductions in PSA levels compared to baseline were 84.37%, 91.48%, 94.67% and 99.81% at 2 weeks, 1 month, 3 months and 6 months after administration of DARO with ADT, respectively. The median time to PSA50, PSA90, significant PSA reduction (PSA <0.2 ng/mL), and PSA nadir (PSA <0.02 ng/mL) was 0.97, 1.27, 1.98, and 2.08 months, respectively. AE mainly included fatigue (two patients) and arm pain (one patient), all of which were grade I or II AE. No grade III or AE were observed. Conclusions: For treating prostate cancer, DARO with ADT has good early efficacy, demonstrating prompt and substantial control of PSA levels, with a favorable safety profile.

A Systemic Review and Meta-analysis of Transabdominal Intravesical Prostatic Protrusion Assessment in Determining Bladder Outlet Obstruction and Unsuccessful Trial Without Catheter.

CONTEXT: Urodynamic study (UDS) provides the most objective assessment of bladder outlet obstruction (BOO) but is impractical to be recommended routinely in outpatient services. Intravesical prostatic protrusion (IPP) had been described to obstruct urinary flow by creating an anatomical ball-valve effect, but there remains a lack of pooled evidence that can objectively correlate with BOO in benign prostatic hyperplasia. OBJECTIVE: To update the current evidence on the predictive role of IPP in determining BOO and unsuccessful trial without catheter (TWOC). EVIDENCE ACQUISITION: A comprehensive literature search was performed to identify studies that evaluated IPP in diagnosing UDS-determined BOO and TWOC. The search included the PubMed/MEDLINE, EMBASE, and Cochrane Library up to January 2021. An updated systemic review and meta-analysis was performed. EVIDENCE SYNTHESIS: A total of 18 studies with 4128 patients were examined. Eleven studies with 1478 patients examined the role of IPP in UDS-determined BOO. The pooled area under the curve (AUC) was 0.83 (95% confidence interval [CI]: 0.79-0.86), and at a cut-off of >10 mm, the sensitivity (Sn) and specificity (Sp) were 0.71 (95% CI: 0.61-0.78) and 0.77 (95% CI: 0.68-0.84), respectively. The probability-modifying plot revealed positive and negative likelihood ratios of 3.34 (95% CI: 2.56-4.36) and 0.35 (95% CI: 0.26-0.45), respectively. Seven studies with 2650 patients examined IPP in predicting unsuccessful TWOC, with a pooled AUC of 0.74 (95% CI: 0.70-0.84), with Sn of 0.51 (95% CI: 0.43-0.60) and Sp of 0.79 (95% CI: 0.73-0.84) at an IPP cut-off of >10 mm. Five studies compared prostate volume (PV) and IPP and revealed a lower AUC of PV at 0.71 (95% CI: 0.67-0.75), which was an inferior parameter in diagnosing BOO (p < 0.001). CONCLUSIONS: This systemic review provided evidence that IPP is a reliable clinical parameter that correlates strongly with underlying BOO and unsuccessful TWOC. PATIENT SUMMARY: In this review, we comprehensively reviewed all the literature to date on evaluating the clinical utility of intravesical prostatic protrusion (IPP). We have demonstrated that IPP correlates strongly with urodynamic study (UDS)-determined bladder outlet obstruction and failure of trial without catheter (TWOC). Outpatient IPP measurement is a quick, inexpensive, and reproducible clinical parameter that can determine the severity of benign prostatic hyperplasia. The clinical role of IPP in predicting failure of TWOC selects patients who are best treated with aggressive surgical approaches rather than conservative medical therapies. More importantly, IPP can facilitate the discriminatory use of invasive UDS, reserved for patients with a strong suspicion of concomitant detrusor abnormalities.

Comparative study of surgical orchidectomy and medical castration in treatment efficacy, adverse effects and cost based on a large prospective metastatic prostate cancer registry.

INTRODUCTION: Androgen deprivation therapy (ADT) remains the mainstay of treatment for metastatic prostate cancer (mPCa) but is associated with significant morbidities. Comparisons of medical castration (MC) and surgical orchidectomy (SO) have yielded varied results. We aimed to evaluate the oncological outcomes, adverse effect (AE) profiles and costs of MC and SO in patients with mPCa. METHODS AND MATERIALS: We reviewed 523 patients who presented with de novo mPCa from a prospectively maintained prostate cancer database over 15 years (2001-2015). All patients received ADT (either MC or SO) within 3 months of diagnosis. The data were analyzed with chi-square, binary and logistics regression models. RESULTS: One hundred and fifty one (28.9%) patients received SO while 372 (71.1%) patients had MC. The median age of presentation was 73 [67 -79] years old. The median prostate-specific antigen (PSA) was 280ng/ml [82.4-958]. Three hundred and thirty one patients (66.3%) had high volume bone metastasis and 57 patients (10.9%) had visceral metastasis. Clinical demographics and clinicopathological were similar across both groups. Similar oncological outcomes were observed in both groups. The proportion of PSA response (PSA <1ng/ml) was 65.6% for SO and 67.2% for MC (P = 0.212). Both therapies achieve >95% of effective androgen suppression (testosterone <50ng/dL). Time to castrate-resistance was similar (18 vs 16 months, P = 0.097), with comparative overall survival (42 vs. 38.5 months, P = 0.058) and prostate cancer mortality (80.1 vs. 75.9%, P = 0.328). Similarly, no difference was observed for the 4 AE profiles between SO and MC respectively; change in Haemoglobin (-0.75 vs. -1.0g/dL, P = 0.302), newly diagnosed Diabetes mellitus (4.6 vs. 2.9%, P = 0.281), control measured by HbA1c (0.2 vs. 0.25%, P = 0.769), coronary artery disease events (9.9 vs. 12.9%, P = 0.376) and skeletal-related fractures (9.3 vs. 7.3%, P = 0.476). After adjusting for varying governmental subsidies and inflation rates, the median cost of SO was $5275, compared to MC of $9185.80. CONCLUSION: Both SO and MC have similar oncological outcomes and AE profiles. However, SO remains a much more cost-effective form of ADT for the long-term treatment of mPCa patients.