External validation of the Rotterdam prostate cancer risk calculator within a high-risk Dutch clinical cohort.

PURPOSE: This study aims to externally validate the Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 and RPCRC-MRI within a Dutch clinical cohort. METHODS: Men subjected to prostate biopsies, between 2018 and 2021, due to a clinical suspicion of prostate cancer (PCa) were retrospectively included. The performance of the RPCRC-3/4 and RPCRC-MRI was analyzed in terms of discrimination, calibration and net benefit. In addition, the need for recalibration and adjustment of risk thresholds for referral was investigated. Clinically significant (cs) PCa was defined as Gleason score ≥ 3 + 4. RESULTS: A total of 1575 men were included in the analysis. PCa was diagnosed in 63.2% (996/1575) of men and csPCa in 41.7% (656/1575) of men. Use of the RPCRC-3/4 could have prevented 37.3% (587/1575) of all MRIs within this cohort, thereby missing 18.3% (120/656) of csPCa diagnoses. After recalibration and adjustment of risk thresholds to 20% for PCa and 10% for csPCa, use of the recalibrated RPCRC-3/4 could have prevented 15.1% (238/1575) of all MRIs, resulting in 5.3% (35/656) of csPCa diagnoses being missed. The performance of the RPCRC-MRI was good; use of this risk calculator could have prevented 10.7% (169/1575) of all biopsies, resulting in 1.2% (8/656) of csPCa diagnoses being missed. CONCLUSION: The RPCRC-3/4 underestimates the probability of having csPCa within this Dutch clinical cohort, resulting in significant numbers of csPCa diagnoses being missed. For optimal performance of a risk calculator in a specific cohort, evaluation of its performance within the population under study is essential.

3D-Reconstructed Contact Surface Area and Tumour Volume on Magnetic Resonance Imaging Improve the Prediction of Extraprostatic Extension of Prostate Cancer.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p < 0.001). Multivariable logistic regression analysis showed that the radiological tumour stage (p = 0.001), tumour volume (p < 0.001), prostate CSA (p < 0.001), and tumour CSA (p ≤ 0.001) were independent predictors of pathological EPE. A 3D reconstruction of tumour locations in the prostate improves prediction of extraprostatic extension. Tumours with a higher 3D-reconstructed volume, a higher surface area of tumour in contact with the prostate capsule, and higher surface area of prostate capsule in contact with the tumour are at increased risk of side-specific extraprostatic extension.

Intraoperative Strategies to Reduce Catheter-Related Bladder Discomfort in the Early Postoperative Period after Robot-Assisted Radical Prostatectomy.

PURPOSE: Catheter-related bladder discomfort occurs in up to 63% of patients following robot-assisted radical prostatectomy. The optimal intraoperative anesthesia regime to prevent patients from catheter-related bladder discomfort is unknown. MATERIALS AND METHODS: A prospective cohort analysis was conducted. Patients with biopsy-proven prostate cancer selected for robot-assisted radical prostatectomy were included between January 2017 and April 2020 from a high volume prostate cancer center. Eight different treatment regimens were compared, ie a combination of general anesthesia and a transversus abdominis plane block with either an additional dose of clonidine or an additional dose of ketamine, or perivesical infiltrations (with 20 ml ropivacaine), or periurethral infiltrations (with ropivacaine); or a dorsal penile nerve block (with 20 ml ropivacaine). Multiple logistic regression and linear mixed models were used to analyze differences in catheter-related bladder discomfort and pain (0-10) at the postoperative recovery unit between the treatment protocols. RESULTS: Of the 391 patients included, those with a combination transversus abdominis plane block, perivesical and periurethral block with ropivacaine had the lowest incidence of catheter-related bladder discomfort, clinically relevant and statistically significantly lower compared to our baseline protocol (transversus abdominis plane block only), ie 36% vs 70%, p=0.001. Overall, patients who were treated with periurethral and/or perivesical infiltrations reported a statistically significantly lower incidence of catheter-related bladder discomfort compared to patients who did not receive this local infiltration (46.5% vs 60.7%, p=0.001). CONCLUSIONS: Perivesical and periurethral injections with ropivacaine have the potential to reduce the incidence of early postoperative catheter-related bladder discomfort by up to 49%. Further randomized studies are necessary to determine the optimal treatment regime to prevent early postoperative catheter-related bladder discomfort.

Feasibility of Image-guided Navigation with Electromagnetic Tracking During Robot-assisted Sentinel Node Biopsy: A Prospective Study.

BACKGROUND AND OBJECTIVE: Image-guided surgical navigation (IGSN) can enhance surgical precision and safety. The expansion of minimally invasive surgery has increased the demand for integration of these navigation systems into robot-assisted surgery. Our objective was to evaluate the integration of electromagnetic tracking with IGSN in robot-assisted sentinel lymph node biopsy (SLNB). METHODS: We conducted a prospective feasibility study to test the use of IGSN in SLNB. In total, 25 patients scheduled for SLNB at The Netherlands Cancer Institute were included (March 2022 to March 2023). SLNB using IGSN was performed using a standardised technique with a da Vinci robot (Intuitive Surgical, Sunnyvale, CA, USA) in four-arm configuration. Feasibility was determined as the percentage of sentinel nodes (SNs) successfully identified via IGSN. Successful SN resection was defined as SNs correctly localised via navigation and validated ex vivo with a gamma probe. Surgeon feedback on the robot-assisted IGSN workflow was evaluated using the System Usability Scale (SUS). KEY FINDINGS AND LIMITATIONS: In accordance with the protocol, the first five patients were used for workflow optimisation, and the subsequent 20 patients were included in the analysis. IGSN led to successful identification of 91% (50/55) of the SNs. There were no complications associated with navigation. The surgeon feedback (SUS) was 60.9, with lowest scores reported for the user interface and workflow integration. CONCLUSIONS: IGSN during robot-assisted surgery was feasible and safe. The technique allowed identification and removal of predefined small pelvic lymph nodes. PATIENT SUMMARY: We carried out a study on the feasibility of imaging-guided navigation in robot-assisted prostate surgery. Our results show that this technique is feasible, safe, and effective.

The appropriateness of PSMA PET/CT in newly diagnosed unfavorable intermediate-risk prostate cancer patients-towards a tumor volume-based risk stratification.

BACKGROUND/OBJECTIVES: This study reassesses the diagnostic value of PSMA PET/CT in unfavorable intermediate-risk prostate cancer (PCa) and validates the Prostate Cancer Network the Netherlands (PCNN) subclassification. SUBJECTS/METHODS: Men subjected to PSMA PET/CT were analyzed, evaluating the incidence of metastatic disease and its correlation with PCNN subgroups. RESULTS: Metastatic disease was identified in 12.4% of patients. Higher PCNN subgroups correlated with increased metastatic potential; odds were significantly lower in low metastatic potential cases (OR: 0.19, 95% CI 0.06-0.62; p = 0.01). CONCLUSIONS: Our findings reaffirm PSMA PET/CT's diagnostic value in unfavorable intermediate-risk PCa and validate the PCNN subclassification, reducing scan burden by 48.1%.

The Probability of Metastases Within Different Prostate-specific Antigen Ranges Using Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer.

Background and objectives: The association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. Methods: In total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitations: The median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels <10 ng/ml and 87.5% in men with PSA levels >100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implications: This is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summary: The prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1.

Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p < 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p < 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA.

A Systematic Review on the Impact of Quality Assurance Programs on Outcomes after Radical Prostatectomy.

BACKGROUND AND OBJECTIVE: The implementation of quality assurance programs (QAPs) within urological practice has gained prominence; yet, their impact on outcomes after radical prostatectomy (RP) remains uncertain. This paper aims to systematically review the current literature regarding the implementation of QAPs and their impact on outcomes after robot-assisted RP, laparoscopic RP, and open prostatectomy, collectively referred to as RP. METHODS: A systematic Embase, Medline (OvidSP), and Scopus search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) process, on January 12, 2024. Studies were identified and included if these covered implementation of QAPs and their impact on outcomes after RP. QAPs were defined as any intervention seeking quality improvement through critically reviewing, analyzing, and discussing outcomes. Included studies were assessed critically using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool, with results summarized narratively. KEY FINDINGS AND LIMITATIONS: Ten included studies revealed two methodological strategies: periodic performance feedback and surgical video assessments. Despite conceptual variability, QAPs improved outcomes consistently (ie, surgical margins, urine continence, erectile function, and hospital readmissions). Of the two strategies, video assessments better identified suboptimal surgical practice and technical errors. Although the extent of quality improvements did not appear to correlate with the frequency of QAPs, there was an apparent correlation with whether or not outcomes were evaluated collectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Current findings suggest that QAPs have a positive impact on outcomes after RP. Caution in interpretation due to limited data is advised. More extensive research is required to explore how conceptual differences impact the extent of quality improvements. PATIENT SUMMARY: In this paper, we review the available scientific literature regarding the implementation of quality assurance programs and their impact on outcomes after radical prostatectomy. The included studies offered substantial support for the implementation of quality assurance programs as an incentive to improve the quality of care continuously.

A Comparison of Globally Applied Prognostic Risk Groups and the Prevalence of Metastatic Disease on Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer.

BACKGROUND: Various risk classification systems (RCSs) are used globally to stratify newly diagnosed patients with prostate cancer (PCa) into prognostic groups. OBJECTIVE: To compare the predictive value of different prognostic subgroups (low-, intermediate-, and high-risk disease) within the RCSs for detecting metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for primary staging, and to assess whether further subdivision of subgroups would be beneficial. DESIGN, SETTING, AND PARTICIPANTS: Patients with newly diagnosed PCa, in whom PSMA-PET/CT was performed between 2017 and 2022, were studied retrospectively. Patients were stratified into risk groups based on four RCSs: European Association of Urology, National Comprehensive Cancer Network (NCCN), Cambridge Prognostic Group (CPG), and Cancer of the Prostate Risk Assessment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The prevalence of metastatic disease on PSMA-PET/CT was compared among the subgroups within the four RCSs. RESULTS AND LIMITATIONS: In total, 2630 men with newly diagnosed PCa were studied. Any metastatic disease was observed in 35% (931/2630) of patients. Among patients classified as having intermediate- and high-risk disease, the prevalence of metastases ranged from approximately 12% to 46%. Two RCSs further subdivided these groups. According to the NCCN, metastatic disease was observed in 5.8%, 13%, 22%, and 62% for favorable intermediate-, unfavorable intermediate-, high-, and very-high-risk PCa, respectively. Regarding the CPG, these values were 6.9%, 13%, 21%, and 60% for the corresponding risk groups. CONCLUSIONS: This study underlines the importance of nuanced risk stratification, recommending the further subdivision of intermediate- and high-risk disease given the notable variation in the prevalence of metastatic disease. PSMA-PET/CT for primary staging should be reserved for patients with unfavorable intermediate- or higher-risk disease. PATIENT SUMMARY: The use of various risk classification systems in patients with prostate cancer helps identify those at a higher risk of having metastatic disease on prostate-specific membrane antigen positron emission tomography/computed tomography for primary staging.

Hypertension secondary to a periprostatic paraganglioma: case report and review of the literature.

BACKGROUND: Around 10 per cent of catecholamine-secreting tumours can be found outside the adrenal medulla (paraganglioma). We report a case of a functional sporadic paraganglioma that was localized lateral to the prostate without causing lower urinary tract symptoms. CASE PRESENTATION: A 76-year old male with an extensive history of cardiovascular disease suffered from hypertension and an unexplained hypochromic microcytic anaemia for years before the coincidental discovery of a 2.5 × 3.5 cm periprostatic mass upon abdominal contrast-enhanced CT scanning. Transrectal biopsies revealed a paraganglioma. The urinary levels of the catecholamine metabolites were found increased. The paraganglioma showed uptake of iodine-123-metaiodobenzylguanidine by SPECT scanning, indicating a solitary lesion. Successful preperitoneal endoscopic resection of the tumour was performed, which resulted in a decrease in blood pressure and a normalization of the urinary catecholamine metabolites. None of the to date known genetic mutations that have been shown to relate to the existence of paragangliomas were identified in the current case. CONCLUSION: An intra- or periprostatic localization of a paraganglioma is very rare. We reviewed the literature and found 6 other cases. Three of the described cases presented with lower urinary tract symptoms. In these three patients, the tumour had a size of 4 cm or larger and in 67 per cent of these cases the paragangliomas were situated within the prostate. The periprostatic region might be considered as a possible location for paragangliomas, especially in the presence of lower urinary tract symptoms even though they were absent in the current case.

Development and clinical applicability of MRI-based 3D prostate models in the planning of nerve-sparing robot-assisted radical prostatectomy.

The interpretation of conventional MRI may be limited by the two-dimensional presentation of the images. To develop patient-specific MRI prostate-based virtual and three-dimensional (3D)-printed models. To assess the association between 3D imaging and the pathological outcome of RARP specimen. To assess the clinical applicability of 3D models to guide nerve-sparing robot-assisted radical prostatectomy (RARP). We created virtual 3D and 3D-printed 3D models of 20 prostate cancer patients retrospectively. A comparison was made between conventional MRI and 3D-reconstructed images. The concordance between tumour lesion location in 3D models and pathology reporting of RARP specimens was assessed. Seven urologists assessed the side-specific extent of nerve-sparing based on (1) conventional MR images, (2) virtual 3D models, and (3) 3D-printed models. Clinically relevant changes in nerve-sparing and the absolute agreement between observers was analyzed using the Chi-square test and intra-class correlation coefficient (ICC). The index lesion was correctly visualized in 19/20 (95%) 3D models and the expected location of extraprostatic extension was correctly visualized in all 3D models. Clinically relevant changes in the planned extent of nerve-sparing between MRI and virtual 3D models and MRI and 3D-printed models were found in 25% and 26%. The ICC of the planned extent of nerve-sparing between urologists was 0.40 (95% CI 0.28-0.55) for conventional MRI, 0.52 (95% CI 0.39-0.66) for virtual 3D models and 0.58 (95% CI 0.45-0.71) for 3D-printed models. 3D models of the MRI prostate to guide RARP could aid urologists in the planning of nerve-sparing surgery as shown by a higher inter-observer agreement.

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study.

Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). Objective: To assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design setting and participants: This was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. Intervention: Patients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysis: The primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitations: At 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. Conclusions: Daily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summary: For patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.

Surgical and Functional Outcomes of Bladder Neck Incision for Primary Vesico-Urethral Anastomosis Stricture after Robot-assisted Radical Prostatectomy are Influenced by the Presence of Pre- or Postoperative Radiotherapy.

OBJECTIVE: To report the intermediate- to long-term outcomes of bladder neck incision (BNI) for vesico-urethral anastomosis stricture (VUAS) after robot-assisted radical prostatectomy (RARP) and the influence of pre- or post-RARP radiotherapy on these outcomes. METHODS: A retrospective cohort study was performed with patients who underwent BNI for VUAS after RARP in a high-volume prostatectomy centre between 2006 and July 2021. Data was collected from patient charts. The cohort was divided into 4 groups: VUAS after (1) RARP-only, (2) RARP, but before salvage radiotherapy (SRT) (VUAS pre-SRT), (3) RARP and after SRT (VUAS post-SRT), and (4) primary radiotherapy and salvage RARP (SRARP). The VUAS recurrence rates, the ability to perform functional transurethral micturition and the post-BNI urinary continence rates were reported. RESULTS: BNI was performed in 90 patients. The median time between first BNI and last follow-up was 32 months (interquartile range 10-58, range 0-171). The majority of VUAS occurred within 6 months after (S)RARP. In those who underwent BNI, recurrent VUAS was reported in 12%, 57%, 29%, and 50% of patients after RARP-only, VUAS pre-SRT, VUAS post-SRT, and SRARP, respectively. Ultimately, transurethral micturition was possible in 94%, 93%, 71%, and 80%, respectively. Severe urinary-incontinence rates (>1 pads/d) were 6%, 16%, 10%, and 29% for RARP-only, VUAS pre-SRT, VUAS post-SRT, and SRARP patients, respectively. CONCLUSION: Primary radiotherapy before RARP and SRT after RARP significantly influenced the success rates of BNI. Those who underwent BNI after SRARP had worse outcomes than patients who underwent RARP only.

The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study.

OBJECTIVE: • To assess the effects of combined therapy with dutasteride and tamsulosin on voiding and storage symptoms compared with those of dutasteride or tamsulosin alone, using 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS: • Men (n = 4844) aged ≥ 50 years with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), a prostate volume of ≥ 30 mL, and a serum prostate-specific antigen level of 1.5-10 ng/mL. • CombAT was a multicentre, double-blind, parallel-group study. • Oral dutasteride (0.5 mg) or tamsulosin (0.4 mg) alone or in combination was taken daily for 4 years. • Mean changes from baseline in storage and voiding symptoms at 4 years were assessed using subscales of the International Prostate Symptom Score. RESULTS: • At 4 years, the mean reduction in the storage subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference -0.43) and tamsulosin (adjusted mean difference -0.96) monotherapy groups (P < 0.001). • Also at 4 years, the mean reduction in the voiding subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference -0.51) and tamsulosin (adjusted mean difference -1.60) monotherapy groups (P < 0.001). • The improvement in the storage subscore with combined therapy was significantly better (P < 0.001) than dutasteride and tamsulosin from 3 months and 12 months, respectively. Similarly, the improvement in the voiding subscore with combined therapy was significantly better than dutasteride (P < 0.001) and tamsulosin (P ≤ 0.006) from 3 months and 6 months, respectively. • Improvements in the storage and voiding symptom subscores with combined therapy were achieved irrespective of prostate volume, although in men with the highest baseline prostate volumes (≥ 58 mL), combined therapy was not better than dutasteride. CONCLUSIONS: • In men with a prostate volume of ≥ 30 mL, combined therapy with dutasteride plus tamsulosin provided better long-term (up to 4 years) control of both storage and voiding LUTS compared with tamsulosin monotherapy. • Combined therapy was better than dutasteride monotherapy in men with prostate volumes of ≥ 30 to < 58 mL, but not in men with a prostate volume of ≥ 58 mL.

Estetrol Cotreatment of Androgen Deprivation Therapy in Infiltrating or Metastatic, Castration-sensitive Prostate Cancer: A Randomized, Double-blind, Phase II Trial (PCombi).

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. OBJECTIVE: To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. DESIGN SETTING AND PARTICIPANTS: A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). INTERVENTION: Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. RESULTS AND LIMITATIONS: Of 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 (p < 0.0001). Total and free T decreased earlier (p < 0.05), and free T was suppressed further (p < 0.05). PSA suppression was more profound and earlier (p < 0.005). FSH levels were suppressed by 98% versus 57% (p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%). CONCLUSIONS: HDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the study reported here. PATIENT SUMMARY: Cotreatment of androgen deprivation therapy with high-dose estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.

Health-related Quality of Life and Pain in a Real-world Castration-resistant Prostate Cancer Population: Results From the PRO-CAPRI Study in the Netherlands.

BACKGROUND: The purpose of this study was to determine generic, cancer-specific, and prostate cancer-specific health-related quality of life (HRQoL), pain and changes over time in patients with metastatic castration-resistant prostate cancer (mCRPC) in daily practice. PATIENTS AND METHODS: PRO-CAPRI is an observational, prospective study in 10 hospitals in the Netherlands. Patients with mCRPC completed the EQ-5D, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Brief Pain Inventory-Short Form (BPI-SF) every 3 months and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Cancer Module (EORTC QLQ-PR25) every 6 months for a maximum of 2 years. Subgroups were identified based on chemotherapy pretreatment. Outcomes were generic, cancer-specific, and prostate cancer-specific HRQoL and self-reported pain. Descriptive statistics were performed including changes over time and minimal important differences (MID) between subgroups. RESULTS: In total, 151 included patients answered 873 questionnaires. The median follow-up from the start of the study was 19.5 months, and 84% were treated with at least 1 life-prolonging agent. Overall, patients were in good clinical condition (Eatern Cooperative Oncology Group performance status 0-1 in 78%) with normal baseline hemoglobin, lactate dehydrogenase, and alkaline phosphatase. At inclusion, generic HRQoL was high with a mean EQ visual analog score of 73.2 out of 100. The lowest scores were reported on role and physical functioning (mean scores of 69 and 76 of 100, respectively), and fatigue, pain, and insomnia were the most impaired domains. These domains deteriorated in > 50% of patients. CONCLUSION: Although most patients were treated with new treatments during follow-up, mCRPC has a negative impact on HRQoL with deterioration in all domains over time, especially role and physical functioning. These domains need specific attention during follow-up to maintain HRQoL as long as possible by timely start of adequate supportive care management.