Impact of frailty on cancer-related fatigue and quality of life in outpatients with prostate cancer: a cross-sectional study of patient-reported outcomes.

OBJECTIVE: To investigate the prevalence of frailty and its effects on cancer-related fatigue and quality of life among patients with prostate cancer. METHODS: In this cross-sectional study, questionnaires were administered to 254 outpatients who visited the Department of Urology at Kagawa University Hospital for prostate cancer; finally, 108 outpatients were analyzed. Frailty, cancer-related fatigue and quality of life were assessed using the G8 screening tool, Japanese version of the Brief Fatigue Inventory and Japanese version of the Short Form 8 Health Survey, respectively. We defined frailty based on a score ≤14 points and divided the patients into frailty and no-frailty groups. We also compared the severity of cancer-related fatigue and quality of life between groups. RESULTS: The prevalence of frailty among 108 outpatients was 63%. Older age correlated with frailty severity (P = 0.0007) but not cancer-related fatigue severity (P = 0.2391). The proportion of patients on treatment or with metastasis was not significantly different between groups. The frailty group had higher cancer-related fatigue severity (P = 0.004) and decreased levels of general activity, mood, walking ability, normal work and enjoyment of life, especially on the Brief Fatigue Inventory subscale. The frailty group had lower physical and mental quality of life than the no-frailty group or general population. CONCLUSIONS: The frailty rate for these patients increased with age, exceeding 60% regardless of the treatment status, and was associated with worsened cancer-related fatigue severity and reduced quality of life. Our study highlights the importance of assessing frailty when selecting treatment, especially in older patients.

Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Impact of the coronavirus disease pandemic on robot-assisted radical prostatectomy and urologists' treatment behaviors: A single tertiary center retrospective study.

OBJECTIVES: To assess whether the coronavirus disease (COVID-19) pandemic affected the outcomes of robot-assisted radical prostatectomy (RARP) and urologists' treatment behaviors. METHODS: We retrospectively examined the medical records of 208 patients who had undergone RARP between August 2017 and December 2022. We compared the rate of preoperative androgen deprivation therapy (ADT), waiting period for RARP, patients' baseline characteristics and quality of life (QOL), proportion of adverse pathology on the RARP specimen, rate of Gleason grade group upgrading from biopsy to the RARP specimen, and prostate-specific antigen (PSA) recurrence-free survival between the pre-pandemic and pandemic groups. RESULTS: The rate of preoperative ADT was significantly higher during than before the COVID-19 pandemic (13.7% vs. 1.9%; p = 0.002). The baseline physical and mental QOL scores did not differ significantly between the groups. The proportion of D'Amico low-risk patients was significantly lower (13.6% vs. 1.2%, p = 0.005) and waiting period for RARP was significantly shorter (median 3.5 months vs. 4.0 months, p = 0.016) in the pandemic group than in the pre-pandemic group. There was no significant difference in the proportion of adverse pathology between the groups (p = 0.104); however, the upgrading rate was significantly higher in the pre-pandemic group (p = 0.002). There was no significant difference in PSA recurrence-free survival between the groups (log-rank, p = 0.752). CONCLUSIONS: The COVID-19 pandemic did not adversely affect the oncologic outcomes of RARP and QOL before RARP. However, it caused urologists to increase the use of preoperative ADT and to reserve RARP for higher-risk cases.

Active surveillance in younger patients with prostate cancer: clinical characteristics including longitudinal patient-reported outcomes.

OBJECTIVE: this study aimed to evaluate the active surveillance continuation period, treatment intervention rate and health-related quality of life in younger patients. METHODS: we prospectively conducted a health-related quality of life survey of patients enrolled in the Prostate Cancer Research International: Active Surveillance-JAPAN study at Kagawa University between January 2010 and December 2020. Health-related quality of life was assessed by mail using a validated Japanese version of the Short-Form 8 Health Survey and Expanded Prostate Cancer Index at active surveillance enrolment and annually thereafter until discontinuation of active surveillance. We divided the patients into two groups, younger (aged <65 years) and older (aged ≥65 years), and compared the two groups. RESULTS: of the 84 patients, 22 were in the younger group. The active surveillance continuation period was shorter in the younger group than in the older group. The 3-year treatment intervention rate was higher in the younger group than in the older group. The majority of the reasons for definitive treatment were related to the protocol, which was similar in both groups (80 versus 76%). The sexual summary scores at active surveillance enrolment were higher in the younger group than in the older group. During active surveillance, the younger group and the older group showed no deterioration in all health-related quality of life scores compared with the scores at the enrolment of active surveillance. CONCLUSIONS: patient-reported health-related quality of life survey indicated that the health-related quality of life of younger Japanese patients was maintained over time during active surveillance, similar to that of older patients.

A national questionnaire survey of Japanese urologists on active surveillance for low- and intermediate-risk prostate cancer.

OBJECTIVE: To conduct a national questionnaire survey of Japanese urologists on active surveillance (AS) for low- and intermediate-risk prostate cancer (PCa). METHODS: A questionnaire was sent to 922 Japanese Urological Association Teaching Base Hospitals. The items included were years of experience as a urologist, sex, workplace, treatment equipment owned, specialty area of daily practice, specialty area of urological cancer, and six hypothetical cases of AS. The cases were categorized by the following Gleason scores: 3 + 3 low risk of PCa, 3 + 4 intermediate risk, and 4 + 3 intermediate risk, with or without comorbidities for each case. Comorbidities were defined as cardiovascular diseases or illnesses warranting anticoagulant therapy. RESULTS: Altogether, 1962 questionnaires were analyzed. Responses were almost equally distributed among all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Percentages of proposed AS for low risk/no comorbidity, low risk/with comorbidity, intermediate-risk 3 + 4/no comorbidity, intermediate risk 3 + 4/with comorbidity, intermediate risk 4 + 3/no comorbidity, and intermediate risk 4 + 3/with comorbidity were 90.5%, 90%, 39.5%, 48.7%, 15%, and 22%, respectively. Analysis of the correspondents' backgrounds showed that the more the urologists' years of experience, the less they were to advise AS of low-risk patients. In the presence of comorbidities, urologists across all age groups tended to propose AS, even in the same Gleason grade group. Cancer center urologists recommended AS more often than their counterparts at general and university hospitals. CONCLUSIONS: Approximately 40% of urologists proposed AS for intermediate-risk cases, confirming that AS for intermediate-risk patients is being considered in Japan.

A national questionnaire survey of Japanese urologists on treatment perspectives for elderly prostate cancer patients.

OBJECTIVE: This study conducted a national questionnaire survey of Japanese urologists from a treatment perspective for older patients with prostate cancer. METHODS: A questionnaire was distributed to 922 teaching hospitals of the Japanese Urological Association. Questionnaire items included years of urologist experience, gender, workplace, treatment equipment owned, daily specialty practice area, urological cancer specialty, treatment reference items for older adults, upper age limit for radical treatment, medication, and two hypothetical cases of Gleason grade group 2 prostate cancer with or without oligometastasis. RESULTS: In total, 1732 questionnaires were analyzed, with responses evenly distributed across all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Performance status was the most frequently mentioned treatment-related item, followed by comorbidities and cognitive function. In addition, geriatric assessment was used by only 13.3% of respondents. No upper age limit was found for total prostatectomy, brachytherapy, and external beam radiation. Anti-androgens, androgen receptor-axis-targeted agents, chemotherapy, poly ADP ribose polymerase inhibitors, and immune-checkpoint inhibitors were selected by 6.8%, 35.6%, 47.3%, 89%, 62.8%, 24.7%, 41.9%, and 41.7% of the respondents, respectively. Response rates for administration of hormone therapy for hypothetical cases of Gleason grade group 2 prostate cancer with or without oligometastases were 96.8% and 61.2%, respectively. CONCLUSIONS: Less than 15% of urologists used geriatric assessments. Several responded that they would set age limits for highly invasive radical and systemic therapies.

A phosphodiesterase 5 inhibitor, tadalafil, suppresses stromal predominance and inflammation in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation is thought to be a major causative factor for the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), which has been used for the treatment of BPH-LUTS in daily practice, is known to act at several urinary organs. In this study, focused on the prostate, we examined the effect of tadalafil on the pathological changes and inflammatory factors in a rat nonbacterial prostatitis (NBP) model. METHODS: Forty ten-month-old male Wistar rats were divided into nonbacterial prostatitis (NBP), NBP with tadalafil treatment (NBP-tadalafil), control, and control treated with tadalafil (control-tadalafil) groups (n = 10 per group). The NBP and NBP-tadalafil groups were castrated and then received daily subcutaneous 17ß-estradiol for 30 days. The control-tadalafil and NBP-tadalafil groups were administered daily oral tadalafil for 30 days. All rats were then sacrificed and pathological changes and inflammatory factors were assessed in the prostatic tissues. RESULTS: In the NBP group, the stroma-to-epithelium (S/E) ratio in the ventral prostate was significantly higher than in the control group (P < 0.001). In the NBP-tadalafil group, the S/E ratio was significantly lower than in the NBP group (P < 0.001). The macrophage levels and the extent of T-cell infiltration in the NBP-tadalafil group were significantly lower than in the NBP group (P < 0.005; P < 0.001, respectively). Compared with the NBP group, tissue concentrations of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-8, and interleukin-1ß, were significantly downregulated in the NBP-tadalafil group (P < 0.01; P < 0.05; P < 0.005, respectively). CONCLUSIONS: Tadalafil suppressed stromal predominance and showed anti-inflammatory effects in a rat NBP model in association with downregulation of inflammatory cytokines.

Usefulness of fluorescent ureteral catheter during laparoscopic residual ureterectomy.

Introduction: There have been reports of surgery for residual ureteral tumors, most of them involved open surgeries. Herein, we report a case of retroperitoneal scopic left ureteral resection and partial cystectomy, performed by placing a fluorescent ureteral catheter in the residual ureter. Case presentation: A 79-year-old man was admitted to our hospital with a chief complaint of gross hematuria. He had undergone transperitoneal left radical nephrectomy due to angiomyolipoma 20 years ago. Computed tomography and Magnetic resonance imaging revealed a solid tumor in the left residual ureter. Retroperitoneal scopic residual ureterectomy has been performed. During the operation, a fluorescent ureteral catheter proved to be very helpful in detecting the ureter. Conclusion: A fluorescent ureteral catheter is considered to be a useful tool in laparoscopic surgery, especially in cases where identification of the ureter is expected to be difficult, such as the residual ureter in this case.

Successful laparoscopic retroperitoneal tumor resection using mixed reality and guiding marker techniques.

Introduction: Small tumors may be difficult to identify visually and require preoperative effort to locate. Recent advancements in mixed reality technology have improved surgical accuracy in various departments. Here, we present the application of mixed reality-assisted surgery and a guiding marker in the case of small retroperitoneal metastasis of uterine cancer. Case presentation: A 67-year-old female with a history of uterine cancer had a retroperitoneal metastasis in the lateroconal fascia near the right diaphragm, measuring 2 cm and infiltrating the peritoneum. We performed precise surgical planning using the preoperative mixed reality software "Holoeyes" on a head-mounted display called HoloLens2. Novel techniques, including ultrasonography-guided placement of a guiding marker and strategic port-site placement facilitated by HoloLens2, ensured accurate tumor identification and laparoscopic resection with minimal blood loss and no intraoperative complications. Conclusion: The use of mixed reality-assisted surgery and a guiding marker effectively enhanced the precision of retroperitoneal tumor resection.

Oral 5-aminolevulinic acid administration before transurethral resection of bladder tumor induces perioperative nausea and vomiting.

BACKGROUND: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting. METHODS: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting. RESULTS: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01). CONCLUSIONS: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application.

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort.

BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.

Ureteroiliac artery fistula caused by full-length metallic ureteral stenting in a malignant ureteral obstruction: a case report.

BACKGROUND: The metallic stent is a new device for relieving the urinary tract in patients with malignant ureteral obstruction with short life expectancy and has been used frequently worldwide for its efficacy and safety. A ureteroarterial fistula with indwelling ureteral stent is rare but highly fatal, and there are several reports of ureteroarterial fistula treated by conventional polymer stents, although there are no reports on metallic stents. To our knowledge, this paper describes the first case of a ureteroiliac artery fistula caused by a full-length metallic ureteral stent in malignant ureteral obstruction. CASE PRESENTATION: Our patient was a 57-year-old Asian woman with a history of locally advanced cervical cancer who underwent abdominal total hysterectomy and chemoradiotherapy. She was diagnosed with right hydronephrosis and hydroureter secondary to upper ureteral obstruction because of retroperitoneal lymph node metastasis. A urinary tract obstruction after placement of 12 months of polymer stent followed by 18 months of metallic stent was relieved, consequently resulting in intermittent gross hematuria with bladder tamponade and anemia. Contrast-enhanced computed tomography could not reveal a ureteroarterial fistula; however, retrograde pyelography emphasized the existence of a ureteroiliac artery fistula. The patient underwent successful endovascular heparin-bonded stent graft placement, and her gross hematuria disappeared thereafter. CONCLUSION: The metallic stent is a useful device for patients with malignant ureteral obstruction with a short life expectancy, although it may impose a higher pressure on the extraureteral tissue than conventional polymer stents due to its properties and may cause a ureteroarterial fistula. The narrowing of the external iliac artery diameter visualized by computed tomography may be helpful for predicting ureteroarterial fistulas.