Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open-label, phase 2 trial.

BACKGROUND: Teverelix drug product (DP) is a novel injectable gonadotropin-releasing hormone antagonist. METHODS: An adaptive phase 2, open-label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6-weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.5 ng/mL at Day 28 with a target castration rate of 90%. Injection sites were inspected by the investigator at every visit and reactions (ISRs) were proactively recorded. RESULTS: The target castration rate was reached in Group 2 (97.5%) but not in Group 1 (62.5%). The castration rates were not maintained to Day 42 (Group 2: 82.5%; Group 1: 50.0%). Suppression of testosterone to castrate levels occurred rapidly (median time: 2 days for both groups). Suppression of testosterone, prostate-specific antigen, follicle-stimulating hormone, and luteinizing hormone was sustained throughout the treatment period, being more prominent with the higher dose. The adverse event (AE) profile was similar between groups. The most common AEs were injection-site induration (n = 40: 80.0%), injection-site erythema (n = 35: 70.0%), and hot flush (n = 21: 42.0%). Most ISRs were Grade 1. CONCLUSION: Overall, the teverelix DP doses were generally well-tolerated but did not adequately maintain castration levels.

Prostatic Artery Embolization as a Treatment Option for Symptomatic Benign Prostatic Hyperplasia: Results from the Prospective Follow-Up Study in Lithuania.

Background: The endovascular treatment of symptomatic benign prostate hypertrophy (BPH) by prostatic artery embolization (PAE) is one of the new treatments proposed. PAE is a minimally invasive alternative that has been shown to successfully treat lower urinary tract symptoms in BPH patients by causing infarction and necrosis of hyperplastic adenomatous tissue, which decompresses urethral impingement and improves obstructive symptoms. The aim of this study was to evaluate the effectiveness and efficacy of PAE in relieving symptoms in patients with symptomatic BPH. Materials and Methods: The material for the study was collected from 2019 to 2022. A total of 70 men with BPH and PAE were studied. Patients underwent an urological examination to measure the International Prostate Symptom Score (IPSS), Quality of Life score (QoL), International Index of Erectile Function short form (IIEF-5), uroflowmetry with Qmax, prostatic volume (PV), and post-void residual volume (PVR) measurements. Statistical analysis for dependent samples was applied. Measured parameters at 2 months and 6 months follow-up were compared to baseline. Results: At baseline, the age of the male (N = 70) subjects was 74 ± 9.6 years with a median of 73.8, but fluctuated from 53 to 90 years. The mean of PV was almost 111 mL and the Qmax was close to 7.7 mL/s. The average PVR was 107.6 mL. The IPSS score mean was 21.3 points and the QoL score was 4.53 points. The IIEF-5 questionnaire score was almost 1.8 points, which shows severe erectile dysfunction. The mean value of the PSA level was 5.8 ng/mL. After 2 and 6 months of PAE, all indicators and scores except erectile function significantly improved. Conclusions: The outcomes of our study show promising results for patients with benign prostatic hyperplasia after PAE. The main prostate-related parameters (PV, Qmax, PVR, IPSS) improved significantly 6 months after embolization.

Incidence, mortality and survival trends of penile cancer in Lithuania 1998-2017.

Background and objectives: The aim of this study was to analyse trends in penile cancer incidence, mortality, and relative survival in Lithuania during the period of 1998-2017. Materials and methods: The study was based on all cases of penile cancer reported to the Lithuanian Cancer Registry between 1998 and 2017. Age-specific rates standardized rates were calculated, using the direct method (World standard population). The Joinpoint regression model was used to provide estimated average annual percentage change (AAPC). One-year and five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of penile cancer varied between 0.72 and 1.64 per 100 000, with AAPC 0.9% (95% CI -0.8-2.7). The mortality rate of penile cancer in Lithuania during this period varied from 0.18 to 0.69 per 100 000, with AAPC of -2.6% (95% CI -5.3-0.3). Relative one-year survival of patients, diagnosed with penile cancer improved over the time from 75.84% in period 1998-2001 to 89.33% in period 2014-2017. Relative five-year survival rate of patients, diagnosed with penile cancer changed from 55.44% in period 1998-2001 to 72.90% in period 2014-2017. Conclusions: The incidence rates of penile cancer showed an increasing trend, while mortality rates were decreasing in Lithuania during 1998-2017. One-year and five-year relative survival increased, however, it does not reach the highest scores of Northern European countries.

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial.

BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. OBJECTIVE: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. DESIGN, SETTING, AND PARTICIPANTS: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. INTERVENTION: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. RESULTS AND LIMITATIONS: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26-0.55]; PSADT ≤6 mo, 0.41 [0.33-0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. CONCLUSIONS: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. PATIENT SUMMARY: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions.

Effect of Clinical Parameters on Risk of Death from Cancer after Radical Prostatectomy in Men with Localized and Locally Advanced Prostate Cancer.

Background: The study aimed to assess predictors and to identify patients at increased risk of prostate-cancer-specific mortality (CSM) after radical prostatectomy (RP). Methods: A total of 2421 men with localized and locally advanced PCa who underwent RP in 2001−2017 were included in the study. CSM predictors were assessed using multivariate competing risk analysis. Death from other causes was considered a competing event. Cumulative CSM and other-cause mortality (OCM) were calculated in various combinations of predictors. Results: During the median 8 years (interquartile range 4.4−11.7) follow-up, 56 (2.3%) of registered deaths were due to PCa. Cumulative 10 years CSM and OCM was 3.6% (95% CI 2.7−4.7) and 15.9% (95% CI 14.2−17.9), respectively. The strongest predictors of CSM were Grade Group 5 (GG5) (hazard ratio (HR) 19.9, p < 0.0001), lymph node invasion (HR 3.4, p = 0.001), stage pT3b-4 (HR 3.1, p = 0.009), and age (HR 1.1, p = 0.0007). In groups created regarding age, stage, and GG, cumulative 10 years CSM ranged from 0.4−84.9%, whereas OCM varied from 0−43.2%. Conclusions: CSM after RP is related to GGs, pathological stage, age, and combinations of these factors, whereas other-cause mortality is only associated with age. Created CSM and OCM plots can help clinicians identify patients with the most aggressive PCa who could benefit from more intensive or novel multimodal treatment strategies.

Liproca Depot: A New Antiandrogen Treatment for Active Surveillance Patients.

BACKGROUND: There is increasing interest in nonmorbid treatments for low- and intermediate-risk prostate cancer with fewer side effects than surgery or radiotherapy. OBJECTIVE: To investigate the tolerability, safety, and antitumor effects of the intraprostatic NanoZolid depot formulation Liproca Depot (LIDDS AB, Uppsala, Sweden) with antiandrogen 2-hydroxyflutamide (2-HOF) in men with low- or intermediate-risk localized prostate cancer managed with active surveillance. DESIGN, SETTING, AND PARTICIPANTS: This clinical phase 2b trial, LPC-004, involved 61 patients. The 2-HOF-containing formulation Liproca Depot was injected transrectally into the prostate under ultrasound guidance. A single dose of 35% or 45% of the prostate volume (study part 1) and a fixed dose of 16 or 20 ml (study part 2) of the formulation were evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary endpoints were tolerability and the reduction in serum prostate-specific antigen (PSA) 5 mo after injection. Antitumor effects were evaluated with magnetic resonance imaging (MRI) and prostate biopsies. Quality of life was assessed using a validated questionnaire (International Prostate Symptom Score). RESULTS AND LIMITATIONS: All doses were safe and well tolerated, without hormonal side effects. In part 2 of the study, the PSA reduction was greatest for the group receiving 16 ml, with an average decrease of 14%, and 95% of patients had a PSA reduction. Some 78% of patients showed a prostate volume decrease compared to baseline. Prostate MRI and biopsies confirmed stable or reduced lesion size. However, post treatment biopsies were performed at the discretion of the investigator, and not routinely. Most patients were amenable to a second injection. CONCLUSIONS: PSA and prostate volume decreased in most patients. Indications of efficacy were shown by post-treatment MRI and biopsies demonstrating stabilization or regression in the majority of cases. PATIENT SUMMARY: Liproca Depot is a safe, minimally invasive treatment that offers the potential for cancer control in patients with intermediate-risk prostate cancer. Further clinical evaluation is warranted.

Association of gene polymorphisms with women urinary incontinence.

Aim of study was set to investigate the association of women urinary incontinence (UI) with serotonin receptor HTR2A T102C and beta 3-adrenergic receptor ADRB3 Trp64Arg genes polymorphisms. The study included 110 women with Urge, Stress, and Mixed UI types and the control group - 105 continent women. Both groups have filled in the ICIQ-FLUTS questionnaire and their blood genotyping was performed. Urge UI subgroup was older and had higher body mass index (BMI) in comparison to other UI types and control group. More than half of all women had family history of UI in Stress UI and Mixed UI subgroups. The frequency of HTR2A T102C gene polymorphism's minor allele C and genotype CC was significantly more expressed in Urge UI subgroup, as compared with control group (C-77.3 vs 58.7%, p = 0.007 and CC-57.6 vs 31.1%, p = 0.015). The ADRB3 Trp64Arg gene polymorphism did not differ between groups. The regression analysis revealed CC genotype (OR = 3.06, 95% CI: 1.11-8.43; p = 0.030) and allele C (OR = 2.53, 95% CI: 1.16-5.53; p = 0.020) were risk factors for development of Urge UI. We conclude that HTR2A T102C gene polymorphism affected the development of Urge UI.

Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: An analysis of the phase III ARAMIS trial.

BACKGROUND: In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Herein, we present analyses of patient-reported health-related quality of life (HRQoL) outcomes. PATIENTS AND METHODS: This double-blind, placebo-controlled, phase III trial randomised patients with nmCRPC and prostate-specific antigen doubling time ≤10 months to darolutamide 600 mg (n = 955) twice daily or matched placebo (n = 554) while continuing ADT. The primary end-point was MFS; the secondary end-points included OS and time to pain progression. In this analysis, HRQoL was assessed by the time to deterioration using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25) subscales. RESULTS: Darolutamide significantly prolonged time to deterioration of FACT-P PCS versus placebo (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.70-0.91; P = 0.0005) at the primary analysis (cut-off date: 3rd September 2018). Time to deterioration of EORTC QLQ-PR25 outcomes showed statistically significant delays with darolutamide versus placebo for urinary (HR 0.64, 95% CI 0.54-0.76; P < 0.0001) and bowel (HR 0.78, 95% CI 0.66-0.92; P = 0.0027) symptoms. Time to worsening of hormonal treatment-related symptoms was similar between the two groups. CONCLUSION: In patients with nmCRPC who are generally asymptomatic, darolutamide maintained HRQoL by significantly delaying time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo.

Head-to-Head Comparison of Two Nomograms Predicting Probability of Lymph Node Invasion in Prostate Cancer and the Therapeutic Impact of Higher Nomogram Threshold.

Introduction: The aim of the study was to compare the performance of the 2012 Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph node dissection (PLND), to examine their performance and to analyse the therapeutic impact of using 7% nomogram cut-off. Materials and Methods: The study cohort consisted of 807 men with clinically localised prostate cancer (PCa) who underwent open RP with PLND between 2001 and 2019. The area under the curve (AUC) of the receiver operator characteristic analysis was used to quantify the accuracy of the 2012 Briganti and MSKCC nomograms to predict LNI. Calibration plots were used to visualise over or underestimation by the models and a decision curve analysis (DCA) was performed to evaluate the net benefit associated with the used nomograms. Results: A total of 97 of 807 patients had LNI (12%). The AUC of 2012 Briganti and MSKCC nomogram was 80.6 and 79.2, respectively. For the Briganti nomogram using the cut-off value of 7% would lead to reduce PLND in 47% (379/807), while missing 3.96% (15/379) cases with LNI. For the MSKCC nomogram using the cut-off value of 7% a PLND would be omitted in 44.5% (359/807), while missing 3.62% (13/359) of cases with LNI. Conclusions: Both analysed nomograms demonstrated high accuracy for prediction of LNI. Using a 7% nomogram cut-off would allow the avoidance up to 47% of PLNDs, while missing less than 4% of patients with LNI.

Impact of Grade Groups on Prostate Cancer-Specific and Other-Cause Mortality: Competing Risk Analysis from a Large Single Institution Series.

Objective: To assess the risk of cancer-specific mortality (CSM) and other-cause mortality (OCM) using post-operative International Society of Urological Pathology Grade Group (GG) model in patients after radical prostatectomy (RP). Patients and Methods: Overall 1921 consecutive men who underwent RP during 2001 to 2017 in a single tertiary center were included in the study. Multivariate competing risk regression analysis was used to identify significant predictors and quantify cumulative incidence of CSM and OCM. Time-depending area under the curve (AUC) depicted the performance of GG model on prediction of CSM. Results: Over a median follow-up of 7.9-year (IQR 4.4-11.7) after RP, 235 (12.2%) deaths were registered, and 52 (2.7%) of them were related to PCa. GG model showed high and stable performance (time-dependent AUC 0.88) on prediction of CSM. Cumulative 10-year CSM in GGs 1 to 5 was 0.9%, 2.3%, 7.6%, 14.7%, and 48.6%, respectively; 10-year OCM in GGs was 15.5%, 16.1%, 12.6%, 17.7% and 6.5%, respectively. The ratio between 10-year CSM/OCM in GGs 1 to 5 was 1:17, 1:7, 1:2, 1:1, and 7:1, respectively. Conclusions: Cancer-specific and other-cause mortality differed widely between GGs. Presented findings could aid in personalized clinical decision making for active treatment.

Extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome.

BACKGROUND: Prostatitis is the most commonly diagnosed disease in men younger than 50 years and accounts for about 8% of all urologists' consultations. OBJECTIVE: After evaluating clinical trials and demonstrating the efficacy of chronic non-bacterial prostatitis treatment, it remains of clinical importance to continue studies on the use of low-energy extracorporeal shock wave therapy (ESWT) in men. MATERIALS AND METHODS: From May 2017 to April 2018, 40 patients with chronic prostatitis (CP) type IIIB/chronic pelvic pain syndrome (CPPS) were enrolled in the study. The patients underwent ESWT once a week for 4 weeks. RESULTS: The mean age of the patients was 47.8 years. A statistically significant improvement in all the parameters, i.e., the International Prostate Symptom Score (IPSS), the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function (IIEF), was observed at week 4. The effect of the treatment was maintained during the entire 12-week period. The NIH-CPSI total score showed the best improvement at week 4, but a slight deterioration without a statistically significant change was noticed at week 12. The greatest improvement at week 4 was documented for the NIH-CPSI and IPSS (43% and 37%, respectively). At week 12, an improvement of 52% and 39% was recorded for VAS and IPSS, respectively. CONCLUSIONS: Our findings confirmed the effectiveness and safety of ESWT in resistant cases of CPPS in the short term. ESWT is cost-effective, which takes little time or requires a small amount of staff, and is easily conducted.

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide.

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).

External validation of Memorial Sloan Kettering Cancer Center nomogram and prediction of optimal candidate for lymph node dissection in clinically localized prostate cancer.

INTRODUCTION: The aim of our study was to evaluate the external validity of the online Memorial Sloan Kettering Cancer Center (MSKCC) nomogram as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph node dissection (PLND). MATERIAL AND METHODS: The study cohort consisted of 679 men with clinically localized prostate cancer (PCa) who underwent RP with PLND between 2005 and 2017. The area under curve (AUC) of the receiver operator characteristic analysis was used to quantify the accuracy of MSKCC nomogram to predict LNI. The specificity, sensitivity and negative predictive value were calculated to assess LNI probability cut-off. RESULTS: A total of 81 of 679 patients had LNI (11.9%). The AUC of MSKCC nomogram was 79%. Using the cut-off value of 7% (sensitivity 88.9%, specificity 45.2% and NPV 96.8%) a PLND could be omitted in 41% (279/679) of men. However, 3.2% (9/279) of men with LNI would be missed. MSKCC nomogram showed good calibration characteristics and high net benefit at decision curve analysis. CONCLUSIONS: MSKCC nomogram in patients with PCa undergoing PLND has 79% discriminated accuracy for prediction of LNI in our cohort. Using a 7% nomogram cut-off, roughly 40% of men would be spared PLND with minimal risk to miss LNI.

A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients.

OBJECTIVES: To determine the safety, efficacy and pharmacokinetic (PK) profile of a pre-mixed depot formulation of leuprolide mesylate subcutaneous injectable suspension (LMIS) 50 mg for up to 1 year of treatment for subjects with advanced prostate cancer. PATIENTS AND METHODS: In this open-label, multicenter study, prostate cancer patients with indication for androgen ablation therapy received two subcutaneous injection of LMIS 50 mg 6 months apart and were followed for an additional 6 months. Two efficacy primary end points were the percentage of subjects with a serum testosterone level ≤ 50 ng/dL by Day 28 as well as the percentage of subjects with similar testosterone suppression from Day 28 to Day 336. RESULTS: Of the 137 enrolled subjects, 15 (10.9%) subjects did not complete the study, including 5 subjects who terminated early due to an adverse event. By Day 28, 98.5% (95% confidence interval 94.8-99.8) of the subjects achieved a castrate testosterone level. At the end of the study, 97% and 95.9% of the subjects had serum testosterone level ≤ 50 ng/dL and ≤ 20 ng/dL, respectively. LMIS 50 mg significantly reduced serum prostate-specific antigen levels after its first injection and this PSA declination effect remained until the end of the study. No statistically significant change was observed in worsening bone pain or urinary symptom assessments during the study. Hot flush (48.9%) and hypertension (14.6%) were the two most common adverse events reported. CONCLUSIONS: LMIS 50 mg, administered at 6-month intervals, effectively suppressed serum testosterone level, and demonstrated a consistent safety profile.

Impact of the 2014 International Society of Urological Pathology Grading System on Concept of High-Risk Prostate Cancer: Comparison of Long-Term Oncological Outcomes in Patients Undergoing Radical Prostatectomy.

Objective: To investigate the relationship between the new International Society of Urological Pathology (ISUP) grading system, biochemical recurrence (BCR), clinical progression (CP) and cancer related death (CRD) after open radical prostatectomy (RP) and determine whether the 2014 ISUP grading system influences the concept of high-risk prostate cancer (HRPCa). Patients and Methods: A total of 1,754 men who underwent RP from 2005 to 2017 were identified from a database at a single tertiary institution. Histopathology reports were reassessed according to the 2014 ISUP grading system. All preoperative, pathological, and clinical follow-up data were obtained. Univariable and multivariable Cox regression, Kaplan-Meier and log-rank analyses were performed. Results: At a median (quartiles) follow-up of 83 (48-123) months, 446 men (25.4%) had BCR, 77 (4.4%) had CP and 39 (2.2%) died from cancer. Grade groups 1, 2, 3, 4, and 5 were detected in 404 (23%), 931 (53.1%), 200 (11.4%), 93 (5.3%), and 126 (7.2%), respectively. 10-year biochemical progression free survival difference between Grade group 3 and 4 was minor but significant (log-rank p = 0.045). There was no difference between Grade groups 3 and 4 comparing 10-year clinical progression free and 10-year cancer specific survival: p = 0.82 and p = 0.39, respectively. Group 5 had the worst survival rates in comparison with other groups (from p < 0.005 to p < 0.0001) in all survival analyses. Pathological stage (hazard ratio (HR) 2.6, p < 0.001), positive surgical margins (HR 2.2, p < 0.0001) and Grade group (HR 10.4, p < 0.0001) were independent predictors for BCR. Stage and Grade group were detected as independent predictors for CP-HR 6.0, p < 0.0001 and HR 35.6, p < 0.0001, respectively. Only Grade group 5 (HR 12.9, p = 0.001) and pT3b (HR 5.9, p = 0.001) independently predicted CRD. Conclusions: The new ISUP 2014 grading system is the most significant independent predictor for BCR, CP, and CRD. Grade group 3 and 4 had similar long-term disease progression survival rates and could potentially be stratified in the same risk group. High-risk cancer associated only with group 5.

Significance of Time Until PSA Recurrence After Radical Prostatectomy Without Neo- or Adjuvant Treatment to Clinical Progression and Cancer-Related Death in High-Risk Prostate Cancer Patients.

Objective: The aim of our study was to evaluate the impact of time until biochemical recurrence (BCR) after radical prostatectomy (RP) without neo- or adjuvant treatment on clinical progression (CP) and cancer-related death (CRD) in high-risk prostate cancer (HRPCa) patients. Materials and methods: A total of 433 men with clinically HRPCa treated between 2001 and 2017 were identified. HRPCa was defined as clinical stage ≥T2c and/or biopsy Gleason score (GS) ≥8 and/or preoperative prostate specific antigen (PSA) value ≥20 ng/ml. Exclusion criteria were neo- or adjuvant treatment and incomplete pathological or follow-up data. BCR was defined as two consecutive PSA values ≥0.2 ng/ml after RP. CP was identified as skeletal lesions, local or loco-regional recurrence. CRD was defined as death from PCa. All men were divided into two groups according to BCR. The chi-square and t-tests were used to compare baseline characteristics between groups. Biochemical progression free survival (BPFS), clinical progression free survival (CPFS), and cancer-specific survival (CSS) rates were estimated using Kaplan-Meier analysis. Patients with detected BCR were analyzed for prediction of CP and CRD with respect to time until BCR. The impact of baseline parameters on BCR, CP, and CRD was assessed by Cox regression analysis. Results: BCR, CP, and CRD rates were 47.8% (207/433), 11.3% (49/433), and 5.5% (24/433), respectively. Median (quartiles) time of follow-up after RP was 64 (40-110) months. Ten-year BPFS rate was 34.2%; CPFS, 81%; and CSS, 90.1%. Men with detected BCR were analyzed for prediction of CP and CRD with respect to time until BCR. The most informative cutoff for time from RP until CP and CRD was ≤ 1 year (p < 0.008). According to this cutoff, men were divided into two groups: BCR detected within 1 year and after a 1-year period. Ten-year CPFS was 49.8% in men with early BCR vs. 81.1% in men with late BCR; CSS was 70.9 vs. 92.8% (p = 0.001). Multivariable analysis confirmed that time until BCR within 1 year predicts CP (p = 0.005) and CRD (p = 0.03). Conclusions: Early BCR is associated with poorer oncological outcomes. The presented results may help both to improve follow-up strategy and opt for more aggressive multimodal treatment of HRPCa in men with very early BCR.

Age and aggressiveness of prostate cancer: analysis of clinical and pathological characteristics after radical prostatectomy for men with localized prostate cancer.

INTRODUCTION: The aim of this study was to describe age- related prostate cancer (PCa) characteristics in men after radical prostatectomy (RP). MATERIAL AND METHODS: There were 2,373 men who underwent RP for clinically localized PCa between 2002 and 2017 and had complete data that were included into the study. Among them, 315 (13.3%) men aged ≤55 years (GR-1), 1,098 (46.3%) men aged between 56 to 65 years (GR-2) and 960 (40.4%) men aged older than 65 years (GR-3) were identified. All preoperative and pathological parameters were compared between all three groups and between each group separately. High-risk prostate cancer (HRPCa) cases were analyzed separately. Regression analysis was used to evaluate the impact of age on cancer aggressiveness. RESULT: Clinical stage (cT), biopsy Gleason score and D'Amico risk groups were different comparing age-related study groups (all p <0.01), respectively. Preoperatively cT1 and Gleason 6 were in the highest rate for GR-1 in comparison with GR-3: 35.9 vs. 27.1%, p = 0.003 and 65.1% vs. 56.7%, p = 0.008, respectively. Analyzing pathological parameters, only Gleason 9-10 was different between GR-1 and GR-3-3.8 vs. 7.6%, p = 0.02. There were 921 (38.8%) HRPCa cases identified. Age was a significant predictor for HRPCa (p = 0.019) in the regression analysis. The oldest men (GR-3) had up to 1.5 fold increased risk for HRPCa detection in comparison with the youngest one (p = 0.008, HR1.44. 95% CI 1.098-1.87). CONCLUSIONS: Younger, ≤55-year-old men, are more likely to present with less aggressive clinical and pathological PCa features in comparison with the older ones. Increasing age has a significant influence on HRPCa detection after RP.

A Population-Based Analysis of Incidence, Mortality, and Survival in Testicular Cancer Patients in Lithuania.

Background and objectives: The aim of this study was to analyze trends in testicular cancer incidence, mortality, and survival in Lithuania during the period 1998-2013. Materials and Methods: The study was based on all cases of testicular cancer reported to the Lithuanian Cancer Registry between 1998 and 2013. Age group-specific rates and standardized rates were calculated using the direct method (European standard population). The Joinpoint regression model was used to provide the annual percentage change (APC). Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of testicular cancer increased from 1.97 to 3.45 per 100,000, with APC of 2.97% (95% CI 0.9 to 5.1). Incidence rate of seminomas changed from 0.71 to 1.54 per 100,000, with APC of 2.61% (95% CI -0.4 to 5.7), and the incidence rate of non-seminomas increased from 0.84 to 1.83 per 100,000, with APC of 4.16% (95% CI 1.6 to 6.8). The mortality rate of testicular cancer in Lithuania during this period declined from 0.78 to 0.51 per 100,000, with APC of -2.91% (95% CI -5.5 to -0.3). Relative five-year survival ratio for the period 2009-2013 was 89.39% (95% CI 82.2 to 94.4). In our study, the overall five-year relative survival increased slightly (10.1%) from 2004-2008 to 2009-2013 (from 79.3% to 89.4%). Conclusions: A moderate increase of testicular cancer incidence has been observed in Lithuania between the years 1998 and 2013, while the mortality rate decreased. The five-year relative survival increased according to different period estimates; however, the results could have been higher if a multidisciplinary approach to diagnostics and management in the concerned centers had been implemented in Lithuania as in other countries.

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer.

BACKGROUND: Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy. The primary end point was metastasis-free survival, with the presence of metastasis determined by independent central review of radiographic imaging every 16 weeks. RESULTS: In total, 1509 patients underwent randomization (955 to the darolutamide group and 554 to the placebo group). In the planned primary analysis, which was performed after 437 primary end-point events had occurred, the median metastasis-free survival was 40.4 months with darolutamide, as compared with 18.4 months with placebo (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P<0.001). Darolutamide was also associated with benefits with regard to all secondary end points, including overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event. The incidence of adverse events that occurred or worsened during the treatment period and had a frequency of 5% or more or were of grade 3 or higher was similar in the two groups; all such events except fatigue occurred in less than 10% of patients in either group. The percentage of patients who discontinued the assigned regimen because of adverse events was 8.9% in the darolutamide group and 8.7% in the placebo group. Darolutamide was not associated with a higher incidence of seizures, falls, fractures, cognitive disorder, or hypertension than placebo. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, metastasis-free survival was significantly longer with darolutamide than with placebo. The incidence of adverse events was similar for darolutamide and placebo. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).