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.

Primary Renal Angiosarcoma: Rare Tumour with Lethal Outcomes.

Introduction: Renal haemangioma is a benign tumour, and due to its characteristics, it must be distinguished from malignant diseases. We present a clinical case of primary renal angiosarcoma initially mistaken for haemangioma due to their similarity. Case report: A 58-year-old man was admitted to the hospital with suspicion of pulmonary embolism. The patient complained of pain on the left side. An ultrasound and CT scan of the abdomen showed a tumour mass ~20.5 × 17.2 × 15.4 cm in size in the projection of the left kidney. On CT images, there were data for clear cell renal clear cell carcinoma (ccRCC). A left nephrectomy was performed. However, histological examination revealed renal haemangioma. Three months later, the patient presented to the hospital with abdominal and lumbar pain. A CT scan showed multiple small hypoechoic foci up to 2 cm in size in the liver, lungs, and intra-abdominally, with the most data for carcinosis. Histological re-verification of the left kidney showed a renal vascular tumour with pronounced signs of infarction and necrosis with the majority of the evidence supporting angiosarcoma. Despite treatment, the patient's outcome was fatal. Conclusions: Based on the clinical presentation, radiological images and histological examination data, the tumour was initially misdiagnosed as kidney haemangioma. Due to the rarity of this tumour, there are no established treatment protocols or clinical guidelines for managing primary kidney angiosarcoma.

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.).

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.

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.).

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.

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.

Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial.

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a potential precursor of prostate cancer (PCa), and patients with HGPIN are at high risk for PCa development. Objective of our study was to evaluate the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated HGPIN on biopsy. METHODS: This prospective, randomized, phase III, open-label 3-year trial assessed dutasteride versus active surveillance in patients with HGPIN. Patients were randomized to dutasteride 0.5 mg daily or active surveillance. Per-protocol prostate biopsies were performed at 6, 12, 24, and 36 months until cancer detection or study end. The primary end point was cancer-free survival (CFS). An intention-to-treat analysis was done for patients who underwent at least one per-protocol biopsy. An efficacy analysis was done for patients who completed the study. CFS was evaluated using Kaplan-Meier and log-rank analysis. RESULTS: In total, 220 men were randomized (dutasteride, n = 107; surveillance, n = 113). PCa was detected in 47.6: 49.1 % in the surveillance group and 45.9 % in the treatment group (p = 0.66). The detected PCa differentiation by Gleason score (GS) was GS 6 in 76.9 %, GS 7 in 19.8 %, and GS ≥ 8 in 3.3 %, with no difference between groups. The 3-year PCa-free survival was 43.6 % in the surveillance and 49.6 % in the dutasteride group (log rank p = 0.57). Limitations include a relatively high non-adherence rate, open-label design, and baseline sextant biopsy scheme. CONCLUSIONS: Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN.

Factors influencing renal graft survival: 7-Year experience of a single center.

BACKGROUND AND OBJECTIVE: The demand for kidney transplants exceeds the existing supply. This leads to a recently growing interest of research in the area of factors that could prolong graft long-term outcomes and survival. In Lithuania, approximately 90% of kidney transplantations are from deceased donors. Donor organs are received and shared only inside the country territory in Lithuania; therefore, donor data is accurate and precise. This study was performed to present particularities of kidney transplantation data in Lithuania and to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. The aim of this study was to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. MATERIALS AND METHODS: We analyzed the influence of deceased donor and recipient factors and histological findings on the graft function in 186 renal transplant patients. Graft survival was estimated within the first year after transplantation. RESULTS: The donors and recipients were older in worse eGFR group 1 year after transplantation. Dissimilarity of degree of glomerulosclerosis (GS), interstitial fibrosis (IF) and arteriolar hyalinosis (AH) were significant in inferior and superior renal function groups (GS >20% 11.4 vs. 0%, P=0.017; IF 9.3 vs. 0%, P=0.034; AH 69 vs. 26.2%, P<0.001). Nine independent variables were significantly associated with a worse renal transplant function 1 year posttransplantation: AH (OR=6.287, P<0.001), an episode of urinary tract infection (OR=2.769, P=0.020), acute graft rejection (OR=3.605, P=0.037), expanded criteria (OR=4.987, P=0.001), female gender donors (OR=3.00, P=0.014), cerebrovascular disease caused donor brain death (OR=5.00, P=0.001), donor's age (OR=1.07, P<0.001), and recipient's age (OR=1.047, P=0.022). Worse renal graft survival 1 year posttransplantation was associated with a delayed graft function and a higher level of glomerulosclerosis in time-zero biopsy. CONCLUSIONS: Donor factors, such as age, female gender, brain death of cerebrovascular cause and expanded criteria donor status had a significant negative impact on the renal graft function 1 year after transplantation. Recipients' age, urinary tract infection and acute graft rejection episodes after transplantation were associated with a worse kidney function 1 year after transplantation. Lower 1-year graft survival was related to a delayed graft function (DGF) and a higher degree of glomerulosclerosis.

Short ischemia induces rat kidney mitochondria dysfunction.

Renal artery clamping itself induces renal ischemia which subsequently causes renal cell injury and can lead to renal failure. The duration of warm ischemia that would be safe for postoperative kidney function during partial nephrectomy remains under investigations. Mitochondria play an important role in pathophysiology of ischemia-reperfusion induced kidney injury, however relation between ischemia time and mitochondrial dysfunction are not fully elucidated. Thus, the effects of renal ischemia (20 min, 40 min and 60 min) on mitochondrial functions were investigated by using in vitro rat ischemia model. Thus, electronmicroscopy showed that at short (20 min) ischemia mitochondria start to swell and the damage increases with the duration of ischemia. In accordance with this, a significant decrease in mitochondrial oxidative phosphorylation capacity was observed already after 20 min of ischemia with both, complex I dependent substrate glutamate/malate (52%) and complex II dependent substrate succinate (44%) which further decreased with the prolonged time of ischemia. The diminished state 3 respiration rate was associated with the decrease in mitochondrial Complex I activity and the release of cytochrome c. Mitochondrial Ca(2+) uptake was diminished by 37-49% after 20-60 min of ischemia and caspase-3 activation increased by 1.15-2.32-fold as compared to control. LDH activity changed closely with increasing time of renal ischemia. In conclusion, even short time (20 min) of warm ischemia in vitro leads to renal mitochondrial injury which increases progressively with the duration of ischemia.

Does illness perception explain quality of life of patients with prostate cancer?

BACKGROUND: It is licely that illness perceptions can explain variations in quality of life of patients with prostate cancer across different treatment methods and stages. Therefore, the aim of this study was to determine if illness perception can explain variations in quality of life of patients with prostate cancer. MATERIAL AND METHODS: The cross-sectional national-level study was carried out. Quality of life was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Visual Analogue Scale. Illness perceptions were measured by the revised Illness Perception Questionnaire. RESULTS: The response rate was 77.1% (N=501). The variation in global quality of life was explained (32.0%) by levels of emotional representation (ß=-0.126; P=0.023) and consequences (ß=-0.209; P<0.01); physical functioning (27.0%), by consequences (ß=-0.203; P<0.01) and chemotherapy (ß=-2.911; P=0.007); role functioning (37.0%), by emotional representations (ß=-0.198; P<0.01), timeline cyclical (ß=-0.209; P=0.014), and stage of the disease (ß=-0.779; P=0.007); emotional functioning (43.0%), by emotional representations (ß=-0.361; P<0.01) and education level (ß=-0.566; P=0.025); cognitive functioning (34.0%), by educational level (ß=0.714; P=0.005), emotional representations (ß=-0.118; P=0.019), illness coherence (ß=-0.167; P=0.030), consequences (ß=-0.187; P=0.001), and hormonal therapy (ß=-0.778; P=0.049); and social functioning (39.0%), by consequences (ß=-0.320; P<0.01) and combined treatment (ß=-1.492; P=0.016). CONCLUSIONS: Illness perceptions may be important while investigating quality of life in patients with prostate cancer. It may underlie quality-of-life differences in this group of patients and could inform decision makers about the importance of the provision of psychosocial services to patients with prostate cancer.

Comparison of long-term results after nephron-sparing surgery and radical nephrectomy in treating 4- to 7-cm renal cell carcinoma.

OBJECTIVE: The aim of our study was to compare long-term oncological outcomes following nephron-sparing surgery (NSS) and radical nephrectomy (RN) for renal cell carcinoma (RCC) 4 to 7 cm in diameter. MATERIAL AND METHODS: The study included patients who underwent RN or NSS for RCC 4 to 7 cm in diameter between 1998 and 2009. The studied groups were compared with respect to the patients' age, sex, physical status according to the American Society of Anesthesiologists Physical classification, histological type, stage, tumor size, grade, duration of the operation, and complications. Survival was established using the Kaplan-Meier method. The risk factors for survival were analyzed using a multivariate Cox regression model. RESULTS: During the study, 351 patients underwent surgery: 317 patients (90.3%) underwent RN, and 34 (9.7%), NSS. The compared groups differed with respect to tumor size (P=0.001) and stage (P=0.006). The overall estimated 12-year survival was 53.7% after RN and 55.2% after NSS (log-rank test P=0.437). The 12-year cancer-specific survival in the RN and NSS groups was 69.6% and 80.6%, respectively (log-rank test P=0.198). Pathological stage and patients' age were the major factors affecting both overall and cancer-specific survival. The type of surgery (NSS or RN) had no effect on survival. CONCLUSIONS: Our study showed that nephron-sparing surgery is a safe technique compared with radical nephrectomy that ensures good oncological control in the treatment of renal cell carcinoma measuring 4 to 7 cm and may be proposed as the treatment of choice for renal tumors not only up to 4 cm, but also 4 to 7 cm in size.

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.

Factors affecting health-related quality of life in prostate cancer patients.

OBJECTIVE: Prostate cancer is the most common cancer among men in Lithuania. Quality of life (QoL) assessment plays a key role in the evaluation and treatment of cancer patients. The aim of this study was to evaluate factors affecting the QoL of patients with prostate cancer in Lithuania. MATERIAL AND METHODS: A cross-sectional national-level study was performed. QoL was investigated with the EORTC QLQ-C30 questionnaire. Statistical analysis included descriptive statistics, interrelationship analysis between characteristics and multivariate logistic regression to estimate predictors and odds ratios (ORs) for each of the independent variables in the model. RESULTS: The response rate was 74.8% (N = 486). One-quarter of respondents with prostate cancer indicated high QoL scores. Higher QoL scores were given for prostate cancer patients with lower education level [OR = 3.092, 95% confidence interval (CI) 1.007-9.491, p = 0.049], having lower monthly expenses for treatment (OR = 3.653, CI 1.318-10.128, p = 0.013), disease stage II (by patient conveyance) (OR = 10.053, CI 1.015-99.534, p = 0.048), disease stage I (by medical record) (OR = 2.19E + 08, CI 218514200.17-218514200.17, p < 0.001) and in those with undisclosed disease stage (OR = 9.220, CI 1.251-67.965, p = 0.029). CONCLUSIONS: Significant predictors for higher QoL scores were education level, own monthly expenses for treatment and disease stage. Patients with undisclosed disease stage more often had higher QoL scores.

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.

Survival of patients with testicular cancer in Lithuania during 1999-2002.

UNLABELLED: The aim of this study was to evaluate the survival of patients with testicular cancer in Lithuania during 1998-2002 and factors that influenced the survival. MATERIAL AND METHODS: The survival rates of testicular cancer patients were evaluated using the data of the Lithuanian Cancer Registry for 1998-2002. The survival was evaluated using the Kaplan-Meier method and log-rank test in order to compare the survival rates. The observed survival rates were calculated. RESULTS: The 5-year observed survival rate in Lithuania was 71.2% (95% CI, 64.4%-77.5%). The survival of testicular cancer patients depended on age at the time of diagnosis, histology of tumor, stage and extent of disease. CONCLUSIONS: The survival of patients with testicular cancer in Lithuania was substantially lower than in other European countries. The better survival was associated with younger age and lesser extent of metastases.

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.

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.