Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

Difference in symptom manifestation between postmenopausal and premenopausal women in acute uncomplicated cystitis: A multi-institutional pilot study.

Objectives: We aimed to prospectively compare lower urinary tract symptoms in premenopausal and postmenopausal women with acute uncomplicated cystitis before and after antibiotic therapy. Materials and methods: This study included adult women with acute uncomplicated cystitis who visited 4 institutions between 2019 and 2020. After registration, we administered oral antibiotics and prospectively documented the changes in lower urinary tract symptoms from the first visit to a follow-up visit at 1 week using the Core Lower Urinary Tract Symptoms Score (CLSS) questionnaire. Results: After treatment, pyuria disappeared in 60 of the 66 patients (14 premenopausal and 46 postmenopausal). The CLSS total score (range) changed from 13 (3-29) to 4 (0-18) with a significant improvement in all CLSS items. At baseline, nocturia, urgency, and urgency incontinence were more prominent in postmenopausal women than in premenopausal women. In contrast, baseline urethral pain and quality of life index were more severe in premenopausal women than in postmenopausal women. After treatment, the CLSS total score was still higher in postmenopausal women, as reflected by the relatively higher scores for nocturia and urgency, irrespective of the comparable scores for urethral pain and the quality of life index in the 2 groups. Conclusions: Our results suggest that if storage symptoms persist, they should be carefully interpreted according to menopausal status.

[A Case of Detrusor Hyperactivity with Impaired Contractility (DHIC) after Transverse Myelitis].

A 44-year-old man was carried to the hospital in an ambulance because of dyspnea, paralysis and dysuria after signs of the flu. Acute encephalomyelitis was diagnosed by examination of magnetic resonance imaging. Antimicrobial treatment and respirator management was carried out with indwelling of urethral catheter for urinary retention. After improvement of encephalitis, the urethral catheter was removed. However, he still needed medical care because of persistent lower urinary tract symptoms. He complained of urge incontinence and urination frequency. Decrease of functional bladder capacity was noticed in a frequency volume chart. After consulting with our neurologist, acute transverse myelitis was diagnosed from imaging and neurological findings. Pressure flow study (PFS)demonstrated detrusor overactive during the filling phase and insufficient contractility during the voiding phase. We reached the diagnosis of detrusor hyperactivity with impaired contractility (DHIC). We did not introduce clean intermittent catheterization but used the mirabegron instead. Although storage symptoms did not improve on the mirabegron monotherapy, the symptoms improved by solifenacin added. There is a possibility that combination therapy with mirabegron and solifenacin is effective for DHIC.

Ureteral calculi secondary to a gradually migrated acupuncture needle.

We herein presented a case of calculi secondary to a migrated acupuncture needle. A 74-year-old woman with a history of acupuncture therapy for lumbago was referred to our hospital for treatment of ureteral and renal pelvic calculi. Abdominal multi-detector computed tomography scans showed ipsilateral hydronephrosis and two calculi secondary to a migrated acupuncture needle. First, a percutaneous nephrolithotomy was performed to extract two calculi and fine needle fragments from the pelvis. Subsequently, residual needle fragments and calculi in the ureter were then removed by flexible transurethral lithotripsy using a holmium laser. In the present case, the formation of the calculi was caused by a migrated acupuncture needle. Calculi and needle fragments were removed safely endoscopically because the whole calculi and needle fragments were located in the ureteral lumen.

[A Case of Sarcomatoid Squamous Cell Carcinoma of the Penis].

A 74-year-old man presented to our hospital with the swelling of penis in May 2016. Physical examination revealed a goose egg-sized lump at the tip of the penis under foreskin. After dorsal skin incision we confirmed the 7 cm tumor on the inner preputial skin and then resected the tumor with circumcision. Histopathological examination revealed sarcomatoid squamous cell carcinoma of the penis. Computed tomography (CT) revealed swelling of bilateral inguinal lymph nodes, and we performed partial penectomy with bilateral superficial inguinal lymph node dissection in July 2016. Because of the positive surgical margin 2 cm away from the tumor we performed a total penectomy 2 weeks after the previous operation. Histopathological examination revealed no residual tumor and negative inguinal lymph nodes. In about 3 months postoperatively, he presented with a complaint of dyspnea and a CT scan showed right, pleural effusion and multiple lung metastases. He died of cancer 4 months postoperatively.

CLINICAL FEATURES OF 15 PATIENTS UNDER SURVEILLANCE FOR RENAL MASSES.

(Objective) We investigated the clinical features of patients under surveillance for localized renal masses. (Methods) This study was a retrospective analysis of 15 patients who were diagnosed as having clinically localized renal cell carcinoma and were placed under surveillance and 68 patients who underwent immediate radical operation for renal masses. (Results) The age at diagnosis in the surveillance group was significantly higher than in the immediate operation group (median, 81 vs. 65 years, respectively, P<0.01). The Charlson Comorbidity Index in the surveillance group was significantly higher than in the immediate operation group (median, 5 vs. 2, respectively, P<0.01) and 10 patients (67%) had complications, which was one of the reasons for surveillance. The median initial tumor size in the surveillance group was 2.5 cm (1.5-10.1). There was no significant difference in the tumor size between the two groups. During a median follow-up of 19 months (6-55) the median tumor growth rate was 0.29 cm per year (-0.19-0.65) in the surveillance group. Of the 15 patients with computed tomography follow-up, four underwent surgical resection of the renal masses after surveillance. The histological diagnosis was clear cell renal cell carcinoma in all four. During follow-up, two patients died of other causes and one patient had bone metastasis but there was no death related to the renal masses in the surveillance group. (Conclusions) The appropriateness of the surveillance should be considered when we initiate surveillance for patients with renal masses because metastasis was detected in one patient in this study. On the other hand, surveillance may be an acceptable management method for elderly or severely comorbid patients because there were two deaths from other causes in the surveillance group.

[A Case of Sarcomatoid Carcinoma of the Penis].

A 75-year-old man visited our hospital complaining of a foul smelling, painful swelling of the glans of the penis. Physical examination showed a true phimosis and a huge solid mass on the glans under the foreskin. After postectomy and penile tumor biopsy, we performed partial penectomy. Histologically, the tumor was composed of atypical spindle cells arranged in an epithelioid pattern and stained positive for both epithelial and mesenchymal markers. Therefore we diagnosed the tumor as sarcomatoid carcinoma of the penis. One month after surgery, advanced gastric cancer was discovered. Thereafter, cancer rapidly spread throughout the whole body, and he died six months postoperatively.