Testosterone bounce predicts favorable prognoses for prostate cancer patients treated with degarelix.

BACKGROUND: To clarify the clinical roles of changes in testosterone (T) levels with a cut-off level of 20 ng/dL as predictive factors for prostate cancer patients treated with degarelix acetate. METHODS: A total of 120 prostate cancer patients who received hormone therapies with gonadotropin-releasing hormone antagonist degarelix acetate were retrospectively analyzed. The predictive values of nadir T levels, max T levels, T bounce, and other clinical factors were evaluated for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). T bounce was defined as satisfying both nadir serum T levels of <20 ng/dL and max serum T levels of ≥20 ng/dL during hormone therapies. RESULTS: In 120 prostate cancer patients, 16 (13%) patients did not achieve nadir T < 20 ng/dL, and 76 (63%) patients had max T ≥ 20 ng/dL. The median times to nadir T and max T are 108 and 312 days, respectively. T bounce was shown in 60 (50%) patients and is associated with favorable prognoses both for OS (p = 0.0019) and CSS (p = 0.0013) but not for PFS (p = 0.92). While in the subgroup analyses of the patients with the progression of the first-line hormone therapies, T bounce predicts favorable OS (p = 0.0015) and CSS (p = 0.0013) after biochemical recurrence. CONCLUSIONS: The present study revealed that T bounce with cut-off levels of 20 ng/dL is a promising biomarker that predicts OS and CSS for prostate cancer patients treated with degarelix acetate.

The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups.

BACKGROUND: Enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in ARCHES (NCT02677896). While health-related quality of life (HRQoL) was generally maintained in the intent-to-treat population, we further analyzed patient-reported outcomes (PROs) in defined subgroups. METHODS: ARCHES was a randomized, double-blind, placebo-controlled, phase 3 study. Patients with mHSPC received enzalutamide (160 mg/day) plus ADT (n = 574) or placebo plus ADT (n = 576). Questionnaires, including the Functional Assessment of Cancer Therapy-Prostate, Brief Pain Inventory-Short Form, and EuroQol 5-Dimension, 5-Level (EQ-5D-5L), were completed at baseline, Week 13, and every 12 weeks until disease progression. PRO endpoints were time to first confirmed clinically meaningful deterioration (TTFCD) in HRQoL or pain. Subgroups included prognostic risk, pain/HRQoL, prior docetaxel, and local therapy (radical prostatectomy [RP] and/or radiotherapy [RT]). RESULTS: There were several between-treatment differences in TTFCD for pain and functioning/HRQoL PROs. Enzalutamide plus ADT delayed TTFCD for worst pain in the prior RT group (not reached vs. 14.06 months; hazard ratio [HR]: 0.56 [95% confidence interval: 0.34-0.94]) and pain interference in low-baseline-HRQoL group (19.32 vs. 11.20 months; HR: 0.64 [0.44-0.94]) versus placebo plus ADT. In prior/no prior RP, prior RT, prior local therapy, no prior docetaxel, mild baseline pain, and low-risk subgroups, TTFCD was delayed for the EQ-5D-5L visual analog scale. CONCLUSION: Enzalutamide plus ADT provides clinical benefits in defined patient subgroups versus ADT alone, while maintaining lack of pain and high HRQoL, with delayed deterioration in several HRQoL measures.

Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses.

PURPOSE: Enzalutamide plus androgen deprivation therapy has previously been shown to improve clinical outcomes in men with metastatic hormone-sensitive prostate cancer (ARCHES; NCT02677896). Here, we assessed if and how the pattern of metastatic spread impacts efficacy of enzalutamide plus androgen deprivation therapy in men enrolled in ARCHES. MATERIALS AND METHODS: Men with metastatic hormone-sensitive prostate cancer were randomized 1:1 to enzalutamide (160 mg/day) plus androgen deprivation therapy or placebo plus androgen deprivation therapy, stratified by disease volume and prior docetaxel treatment. The primary end point was radiographic progression-free survival. Secondary end points included time to prostate specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event and castration resistance. Post hoc analyses were performed by pattern of metastatic spread based on study entry imaging. RESULTS: Of the overall population with metastases identified at enrollment (1,146), the largest patient subgroups were those with bone metastases only (513) and those with bone plus lymph node metastases (351); there were fewer men with lymph node metastases only (154) and men with visceral±bone or lymph node metastases (128). Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression vs placebo plus androgen deprivation therapy in men with bone metastases only (HR 0.33) and bone plus lymph node metastases (HR 0.31). Similar improvements in secondary end points were also observed in these subgroups. CONCLUSIONS: These findings indicate that treatment with enzalutamide plus androgen deprivation therapy provides improvements in men with bone and/or lymph node metastases but may be less effective in men with visceral patterns of spread.

Enzalutamide with androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer: A subgroup analysis of the phase III ARCHES study.

OBJECTIVE: To evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone-sensitive prostate cancer. METHODS: A post-hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone-sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end-point was radiographic progression-free survival. Secondary end-points included time to prostate-specific antigen progression and overall survival. RESULTS: Of 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end-points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3-4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population. CONCLUSIONS: Enzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone-sensitive prostate cancer, consistent with the overall population.

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: the OCUU-CRPC study.

BACKGROUND: Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared. METHODS: Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate. This trial is registered with ClinicalTrials.gov (NCT02346578) and the University hospital Medical Information Network (UMIN000016301). RESULTS: Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p < 0.001) and 6-month (73.1% vs. 31.4%; p < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05-0.47; p < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15-0.54; p < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively. CONCLUSIONS: As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: study protocol for a multicenter randomized phase II trial (the OCUU-CRPC study).

BACKGROUND: Enzalutamide is an oral androgen receptor targeted agent that has been shown to improve survival in PREVAIL trials and has been approved for patients with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). Meanwhile, flutamide is a non-steroidal oral anti-androgen that was commonly used before the approval of bicalutamide. The objective of the OCUU-CRPC study is to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative anti-androgen therapy (AAT) after combined androgen blockade (CAB) therapy that included bicalutamide in patients with CRPC. METHODS: A total of 100 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day, 4 × 40 mg capsules once daily) and flutamide (375 mg/day; 3 × 125 mg tablets thrice daily) groups. The primary endpoint for the drug efficacy is the response rate of prostate-specific antigen (PSA) (i.e., the ratio of patients whose PSA declined by ≥50% from baseline) at 3 months. Meanwhile, the secondary endpoints are PSA progression rate at 3 and 6 months, PSA response rate at 6 months, change in quality of life, PSA progression-free survival, and safety. The patient registration started in January 2015 and will end in March 2018, and the follow-up period is 6 months after the last patient registration. The main result will be reported in March 2019. DISCUSSION: In the OCUU-CRPC study, we compare the efficacy and safety of enzalutamide or alternative AAT with flutamide in participants with CRPC who were previously treated with a CAB therapy with bicalutamide. The expected results of this study will be that enzalutamide is superior to flutamide in terms of PSA response. A longer time to disease progression with enzalutamide over flutamide may translate to better overall survival. However, flutamide may be more accessible for patients owing to its lower cost than enzalutamide. TRIAL REGISTRATION: The OCUU-CRPC study was prospectively registered at clinicaltrials.gov ( NCT02346578 , January 2015) and University Hospital Medical Information Network ( UMIN000016301 , January 2015).

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: a retrospective study.

BACKGROUND: Alternative anti-androgen therapy (AAT) with flutamide after combined androgen blockade (CAB) therapy with bicalutamide for metastatic prostate cancer is common. However, no studies have compared enzalutamide without AAT with enzalutamide after AAT with flutamide as treatment for castration-resistant prostate cancer (CRPC). We aimed to compare the efficacies of flutamide and enzalutamide for CRPC. METHODS: In our hospital, 55 patients were diagnosed with CRPC after CAB therapy and administered flutamide or enzalutamide between May 2014 and December 2017. Patients with flutamide failure were administered enzalutamide. We evaluated the (1) prostate-specific antigen (PSA) best response with initial therapy, (2) PSA progression-free survival with initial therapy (PSA-PFS), (3) PSA best response with enzalutamide therapy, (4) PSA-PFS of enzalutamide therapy, and (5) overall survival (OS). RESULTS: As first-line therapy, patients were administered enzalutamide (n = 29) or flutamide (n = 26). In the flutamide group, 18 patients showed disease progression and were administered enzalutamide. PSA best response was statistically higher in the enzalutamide group. PSA-PFS was significantly longer in the enzalutamide group [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.19-0.92, p = 0.024]. However, there was no significant difference in PSA best response with enzalutamide therapy and PSA-PFS between the first- and second-line enzalutamide therapies (HR 0.80, 95% CI 0.33-1.94, p = 0.62). There was no significant difference in OS between enzalutamide and flutamide groups (HR 1.85, 95% CI 0.53-6.42, p = 0.33). CONCLUSIONS: AAT with subsequent flutamide after CAB therapy with bicalutamide may be suitable for some CRPC patients.

Chronological changes in epidemiological characteristics of lower urinary tract urolithiasis in Japan.

OBJECTIVES: To determine changes and trends in the annual incidence and epidemiological aspects of lower urinary tract stones in Japan. METHODS: Data about patients who had been diagnosed by urologists in 2015 with first and recurrent lower urinary tract stones were collected from 301 hospitals approved by the Japanese Board of Urology. The estimated annual incidence according to sex, age and stone composition was compared with previous nationwide surveys between 1965 and 2005. RESULTS: The incidence of lower urinary tract stones in Japan has steadily increased from 4.7 per 100 000 in 1965 to 12.0 per 100 000 in 2015. However, the age standardized annual incidence of lower urinary tract stones has remained relatively stable over the same period at 5.5 per 100 000 and 6.0 per 100 000 in 1965 and 2015, respectively. The increase in incidence was most evident among individuals aged ≥80 years. The incidence of calcium oxalate stones has steadily increased among males and females, whereas that of infection-related stones has significantly decreased from 26.2% to 14.3% among men over the past 50 years. CONCLUSIONS: Nationwide surveys suggest a steady increase in the incidence of lower urinary tract stones over a 50-year period in Japan. This trend might reflect changes in the aging population and improved Japanese medical standards.

Comparison of efficacy and toxicity of second-line combination chemotherapy regimens in patients with advanced urothelial carcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicities of second-line chemotherapy regimens with docetaxel and gemcitabine (GD), or paclitaxel and gemcitabine (GP) for advanced or metastatic urothelial carcinoma (UC) that did not respond to first-line platinum-based chemotherapy. METHODS: From 2002 to 2017, 78 patients with metastatic UCs that progressed after platinum-based chemotherapy were treated with either GD (n = 41) or GP (n = 37). We compared these two different regimens by analyzing their efficacy and toxicities in a retrospective manner. RESULTS: Of the 78 patients enrolled in this study, it was possible to determine treatment efficacy in 70; the proportion of patients with objective response and disease control were 8.6 (9/70) and 54.3% (38/70), respectively. The median progression-free survival and overall survival in the total population (GP and GD) were 3.5 (95% CI 0.6-53.3) and 9.6 months (95% CI 1.2-53.3), respectively. There was no significant difference between the two regimens (GD or GP) regarding survival outcomes. Treatment-related adverse events were mostly manageable, but one patient died as a result of febrile neutropenia. The presence of liver metastasis and anemia (Hb < 10.0 g/dl) was prognostic factors for worse survival. CONCLUSIONS: Combination chemotherapy with either GP or GD was a favorable and well-tolerated second-line treatment regimen for patients with advanced or metastatic UC following the failure of a platinum-based regimen. Further study using a large prospective cohort is needed to identify patients who will benefit from second-line combination therapy.

Near infrared fluorescence imaging system for laparoscopic partial nephrectomy.

INTRODUCTION: Recently, the use of indocyanine green (ICG) with near infrared fluorescence (NIRF) imaging has emerged as an alternative technique for the real-time delineation of resection margins during partial nephrectomy (PN). We aimed to assess the feasibility of using NIRF imaging with ICG during laparoscopic partial nephrectomy (LPN) to delineate the margin between normal renal parenchyma and renal cortical tumors. MATERIALS AND METHODS: A retrospective comparison of real-time tumor margin identification and operative outcomes was conducted for 83 patients who underwent LPN with NIRF imaging (IMAGE1 system) and 74 patients who did not. RESULTS: Tumor margins were identified in 82% of cases in the NIRF group, with a rate of 79% for the clear cell renal carcinoma cases only. Volume of blood loss was higher for the NIRF than normal imaging group (p = 0.015), while the warm ischemia time was significantly shorter (p < 0.01) for the NIRF group. There was no significant difference in the pre to postoperative change in estimated glomerular filtration rate (p = 0.38) or rate of severe complications (Clavien grade ≥ 3; p = 0.88). The rate of positive surgical margins was comparable between the groups (3%; p = 0.91). CONCLUSIONS: NIRF imaging with ICG during LPN was safe and feasible, although the surgical outcomes with NIRF alone was not significantly superior to the ones with conventional methods.

Outcomes of indwelling metallic stents for malignant extrinsic ureteral obstruction.

OBJECTIVES: To report the treatment outcomes of patients with extrinsic ureteral obstruction treated with metallic stents and to identify the factors predicting stent failure. METHODS: A total of 52 patients with extrinsic ureteral obstruction as a result of malignancy (66 ureters) were treated with metallic stents (Resonance® ) and included in the study. The median observation period was 118 days. RESULTS: The median survival time of these patients was 210 days, and the stent patency rate was 86.0% at 6 months and 60.0% at 1 year. Eight (15.4%) patients underwent nephrostomy as a result of stent failure. The occlusion rate of bilateral ureteral obstructed cases was significantly higher than that of unilateral cases. There was no correlation between the preoperative serum creatinine level, causes of ureteral occlusions (compression by tumor, lymph node metastasis, peritoneal dissemination), obstructed site (upper, middle, lower ureter) and stent failure. CONCLUSIONS: Metallic stents are excellent in maintaining patency compared with the conventional stents. Therefore, they can be used as first-line treatment of malignant ureteral obstructions.

Chronological changes in the epidemiological characteristics of upper urinary tract urolithiasis in Japan.

OBJECTIVES: To assess epidemiological and chronological trends of upper urinary tract stones in Japan in 2015. METHODS: Patients with a first episode of upper urinary tract stones in 2015 were enrolled in this nationwide survey. The study included all hospitals approved by the Japanese Board of Urology, therefore covering most of the hospitals where urologists practice in Japan. The annual incidence and composition of urolithiasis were evaluated by age and sex. These results were compared with the previous results of the nationwide surveys from 1965 to 2005 to analyze temporal trends. RESULTS: The estimated annual incidence of a first-episode upper urinary tract stone in 2015 was 137.9 (191.9 in men and 86.9 in women) per 100 000. The estimated age-standardized first-episode upper urinary tract stone incidence in 2015 was 107.8 (150.6 in men and 63.3 in women) per 100 000, which did not represent a significant increase since 2005. An equivalent incidence was observed in patients aged >50 years, whereas a reduced incidence was observed in patients aged <50 years in both sexes. The proportion of patients who received percutaneous nephrolithotomy and/or ureteroscopy increased by approximately fivefold in the past 10 years. CONCLUSIONS: The steady increase in the annual incidence of upper urinary tract stones since 1955 leveled off in 2015. The current results show novel trends in the incidence and treatment modalities in the nationwide surveys of urolithiasis in Japan.

Prolonging survival in metastatic renal cell carcinoma patients treated with targeted anticancer agents: a single-center experience of treatment strategy modifications.

INTRODUCTION: We investigated therapeutic outcomes in consecutive patients with metastatic renal cell carcinoma treated with targeted anticancer agents from 2008 to 2014 in order to determine the efficacy of adverse event management for such agents and the best sequence in which to use them. MATERIALS AND METHODS: We analyzed 132 consecutive patients who had taken targeted anticancer agents for metastatic renal cell carcinoma. Of these, 101 patients received therapy between 2008 and 2011 (pioneer group) and 31 patients received therapy between 2011 and 2014 (contemporary group). Patients of the contemporary group were provided with aggressive adverse event management and education on such management, were treated according to a standard therapeutic strategy, and were able to receive axitinib as a second-line drug. We analyzed the incidence of hand-foot syndrome. Furthermore, we compared relative dose intensity between patients in the pioneer and contemporary groups who took sunitinib as first-line therapy. We also compared overall survival between the two groups to determine whether adverse event management improved prognosis. RESULTS: The incidence of hand-foot syndrome was significantly reduced by aggressive adverse event management. Relative dose intensity was significantly higher in the contemporary group than in the pioneer group. Median survival time was significantly longer in the contemporary group than in the pioneer group. CONCLUSION: Our results suggest that aggressive management of adverse events associated with targeted drugs, the use of sunitinib as a first-line therapy, and the availability of axitinib as a second-line therapy all contribute to prolonged survival for metastatic renal cell carcinoma patients.

[Bone and Calcium Research Update 2015. Clinical update of urolithiasis--ESWL (extracorporeal shock wave lithotripsy)].

ESWL (extracorporeal shock wave lithotripsy) is widely used for upper urinary stones and successfully treats most patients with uncomplicated kidney stones. ESWL is still of high strategic importance despite ureteroscopy and PNL occupy an essential place in the treatment of urinary stones by technologic advancements. However ESWL is just one of treatment tool and the best procedure should be selected for the patients. Moreover urolithiasis is one of lifestyle-related diseases and should be treated as systemic illness in the daily medical practice.

Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumour antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides.

OBJECTIVE: To analyse and then generalize the mechanism by which partial or complete response is achieved among a limited number of patients with metastatic renal cell carcinoma (RCC) treated with interferon or interleukin-2. MATERIALS AND METHODS: An expression library of RCC (clear-cell carcinoma) was screened using the sera of patients with metastatic RCC who benefited from partial or complete response to cytokine therapy, the postulation being that those remarkable responders obtained specific cellular immunity against RCC with the antibodies to react with the cancer antigen. Peripheral blood mononuclear-cells (PBMCs) from healthy volunteers were stimulated with the antigen-derived peptides to induce specific cytotoxic T lymphocytes (CTLs). Specific activities of CTLs were measured by 5¹Cr-releasing assay. RESULTS: Among 15 positive clones isolated, two novel genes, galectin 9 and PINCH, were expressed at much higher levels in cancerous lesions than in normal tissues in all the patients with clear-cell carcinoma who were examined. Both HLA-A*2402-restricted and HLA-A*0201-restricted CTLs were induced by each antigen-derived peptide to exhibit specific and highly cytotoxic activities towards RCC cells. Specific CTLs were induced abundantly, as shown by flow cytometry analysis of the CTLs labelled with fluorescein isothiocyanate anti-CD107a and APC anti-CD8. The clonal expansion of the CTLs was shown by the clonality of T-cell receptor Vß repertoires. CONCLUSION: A novel approach based on clinical observations yielded promising tumour antigens as immunotherapy targets of RCC.

Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged <75 and ≥75 Years: ARCHES Post Hoc Analysis.

BACKGROUND: In ARCHES, treatment intensification of androgen deprivation therapy (ADT) with enzalutamide versus placebo improved clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Understanding the benefits and tolerability of enzalutamide for men aged ≥75 yr may inform disease management. OBJECTIVE: To determine whether age is associated with clinical outcomes in mHSPC. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of the multinational, double-blind, randomized, placebo-controlled, phase 3 ARCHES trial in 1150 men with mHSPC (median follow-up [mo]: <75 yr, 44.6; ≥75 yr, 44.3) was performed. INTERVENTION: Randomization 1:1 to enzalutamide (160 mg/d) plus ADT or placebo plus ADT; stratification by disease volume and prior docetaxel use. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), radiographic progression-free survival (rPFS), safety, and other secondary endpoints were compared between age groups (<75 and ≥75 yr) and treatment arms (Cox proportional hazard models). RESULTS AND LIMITATIONS: Men aged <75 versus ≥75 yr had longer OS (enzalutamide plus ADT: hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.47-0.91; p = 0.02; placebo plus ADT: HR 0.81; 95% CI 0.60-1.09; p = 0.13) and rPFS (enzalutamide plus ADT: HR 0.78; 95% CI 0.58-1.04; p = 0.12; placebo plus ADT: HR 0.98; 95% CI 0.74-1.30; p = 0.007). Enzalutamide improved OS (<75 yr: HR 0.61; 95% CI 0.47-0.79; ≥75 yr: HR 0.76; 95% CI 0.54-1.09) and secondary efficacy endpoints without evidence of statistical heterogeneity, and was generally well tolerated in both age groups, with minimal quality-of-life impact. Older versus younger patients experienced more frequent dose interruptions (20.2% vs 10.9%) and treatment-emergent adverse events (95.2% vs 89.1%). Post hoc examination and small sample size preclude definitive conclusions. CONCLUSIONS: Enzalutamide plus ADT improved efficacy outcomes and was generally well tolerated despite shorter treatment exposure in older patients, indicating enzalutamide's utility in patients with mHSPC aged <75 and ≥75 yr. PATIENT SUMMARY: Enzalutamide is a drug approved to treat men with prostate cancer. In this report, we compared patients aged <75 and ≥75 yr treated with enzalutamide plus androgen deprivation therapy to determine whether age affected how long they lived without the cancer spreading to other parts of their body. We found that, although younger patients had more favorable survival outcomes, enzalutamide was associated with longer survival and reduced disease spread in both age groups.

The Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES.

BACKGROUND: Few phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk of undertreatment. OBJECTIVE: To evaluate outcomes for patients with oligometastatic and polymetastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of data for 927 patients with nonvisceral metastatic HSPC in the ARCHES trial (NCT02677896). INTERVENTION: Patients were randomized 1:1 to enzalutamide (160 mg/d orally) plus ADT or placebo plus ADT with HSPC categorized as oligometastatic (1-5 metastases) or polymetastatic (≥6 metastases). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The treatment effect on radiographic progression-free survival (rPFS), overall survival (OS), and secondary efficacy endpoints was evaluated in terms of the number of metastases. Safety was assessed. Cox proportional hazards models were used to generate hazard ratios (HRs). The Brookmeyer and Crowley method was used to generate 95% confidence intervals (CIs) for Kaplan-Meier median values. RESULTS AND LIMITATIONS: Enzalutamide plus ADT improved rPFS (HR 0.27, 95% CI 0.16-0.46; p < 0.001), OS (HR 0.59, 95% CI 0.40-0.87; p < 0.005), and secondary endpoints in patients with oligometastatic or polymetastatic disease (rPFS: HR 0.33, 95% CI 0.23-0.46; p < 0.001; OS: HR 0.55, 95% CI 0.41-0.74; p < 0.001). Safety profiles were generally similar across subgroups. Limitations include the small numbers of patients with fewer than three metastases. CONCLUSIONS: This post hoc analysis demonstrated the utility of enzalutamide, irrespective of metastatic burden or type of oligometastatic disease, and suggests that earlier treatment intensification with systemic potent androgen receptor inhibition is advantageous. PATIENT SUMMARY: This study considered two treatment options for metastatic hormone-sensitive prostate cancer in patients with one to five metastases or six or more metastases. Treatment with enzalutamide plus ADT improved survival and other outcomes over ADT alone, whether patients had few or many metastases.

Descriptive study on burden and communication of fatigue among castration-resistant prostate cancer patients in Japan.

OBJECTIVE: Prostate cancer is a common malignancy and patients may progress to castration-resistant prostate cancer (CRPC). Among patients with CRPC, fatigue is a common symptom associated with current treatments. The aim of this real-world study was to describe patient-reported fatigue in Japanese patients treated with androgen receptor-axis-targeted therapies for CRPC. METHODS: Data of this observational study were collected in a quantitative phase for the description of patient-reported fatigue, and a qualitative phase for elicitation of fatigue perception and barriers to reporting fatigue. RESULTS: In the quantitative phase (N = 22), fatigue was investigated in two formats: symptoms report and Brief Fatigue Inventory (BFI). In the report of the symptoms, 12 patients reported tiredness, and four moderate-to-severe tiredness during treatment. In the BFI, all patients reported fatigue; eight reported moderate-to-severe fatigue. The most affected BFI domain was mood: five patients reporting moderate-to-severe impact. In interviews (qualitative phase; N = 8), diverse patient experience on fatigue was observed, including apathetic feelings, affected speed and distance during the walk, negative impact on profession, housework, or driving, reduced outgoing activity, and difficulty in enjoying time with grandchildren or travel. Five out of eight patients communicated fatigue to their physicians but received diverse reactions. CONCLUSION: Patient interviews highlighted the impact of fatigue on patients' lives and difficulties in communicating fatigue to physicians. Fatigue frequency after medication may need to be monitored and its burden is considered to provide treatment that meets the needs, wishes, and circumstances of each patient. Further research is needed to elucidate how fatigue affects patients' lives, and underscore patient-physician communication difficulties.

Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.