Nihon Hinyokika Gakkai zasshi. The japanese journal of urology最新文献

(Purpose) We performed a clinical retrospective study on the evaluation of pembrolizumab treatment results for advanced urothelial cancer in our hospital. (Materials and Methods) Twenty-seven patients diagnosed with advanced or metastatic urothelial carcinoma who received pembrolizumab between April 2018 and December 2021 were included. We retrospectively reviewed medical records to examine treatment outcomes, immune-related adverse event (irAE), and prognostic factors. (Results) The median age of patients was 76 years, and the median number of pembrolizumab doses was 6. The median overall survival was 8.8 months, and the best treatment response according to RECIST version 1.1 was complete response 1, partial response 7, stable disease 5, and progression disease 14. Pre-pembrolizumab risk factors related to overall survival include the presence of liver metastasis, LDH ≥200 IU/L, and TSH <4 μIU/mL in univariate analysis. Grade 3 irAE was type 1 diabetes in only 1 case, and grade 2 were hypothyroidism in 4 cases, type 1 diabetes in 1 case, interstitial pneumonia in 1 case, and skin disorder in 1 case. Nine patients had a TSH of 4 μIU/mL or higher at the start of pembrolizumab, and four of them had hypothyroidism requiring oral levothyroxine, and none of the patients in the low TSH group required hormone replacement (p =0.013). (Conclusion) High TSH level before pembrolizumab administration for advanced urothelial cancer was associated with hypothyroidism, suggesting the possibility of improved prognosis.

(Purpose) Enfortumab vedotin has been available as a third-line treatment for advanced urothelial carcinoma in Japan since December 2021. While the treatment is expected to improve the outcome of advanced urothelial carcinoma, concerns regarding adverse events do exist. We report here our initial experience of the use of enfortumab vedotin as a third-line therapy in patients with advanced urothelial carcinoma. (Patients and Methods) We retrospectively evaluated the efficacy and adverse events of enfortumab vedotin treatment, as a third line therapy, in patients who had failed platinum-containing chemotherapy and immune checkpoint inhibitor therapy in our institution from January 2022 to January 2023. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and duration of response (DOR). Safety was evaluated for treatment-related adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. (Results) In this study, sixteen patients were investigated. The median age was 70 years (45-93 years); all patients had previously received platinum-containing chemotherapy with cisplatin or carboplatin, eleven having been treated with pembrolizumab, and 5 with avelumab, as sequential immune checkpoint inhibitors. As for efficacy, the median observation period was 9.27 months (4.03-16.6 months). The treatment response rate included 2 complete response (CR) (12.5%), 5 partial response (PR) (31.3%), and 5 stable disease (SD), out of 16 patients. The ORR and DCR were 43.8% and 75.0%, respectively. The median PFS was 7.77 months (3.67-not reached). The median time to response was 1.87 months (0.47-2.80 months) and the median DOR was 7.93 months (0.73-13.1 months). Eight patients (50%) discontinued treatment due to disease progression. As for safety, the incidence of treatment-related adverse events (TRAE) was 93.8%, and that of Grade 3 or higher TRAE was 56.3%. Four out of 16 patients (25%) underwent dose reduction due to TRAE. Among all grades, skin reactions were the most common in 12 patients (75%), followed by dysgeusia, alopecia, neutropenia, and anorexia. Neutropenia (including febrile neutropenia) was the most common Grade 3 or higher TRAE in five patients (31.3%), followed by skin reactions, anorexia, and anemia. Two of the patients, who observed skin reactions, developed severe rash and Stevens-Johnson syndrome, which eventually led to treatment discontinuation. The median time from enfortumab vedotin administration to onset of skin reaction was 9 days (5-18 days), with most cases occurring in the first cycle. (Conclusions) Enfortumab vedotin is an effective treatment option in real clinical practice. However, adverse events, including skin reactions, should be carefully monitored.

We report the case of a 41-year-old man who presented with gross hematuria and a bladder tumor on ultrasonography. Magnetic resonance imaging indicated a possible muscle-invasive bladder cancer or urachal carcinoma. Following transurethral resection of the bladder tumor, histopathological findings revealed an adenocarcinoma similar to colorectal cancer. The patient was diagnosed with an urachal carcinoma in the urinary bladder dome. Since multiple lung metastases were observed on computed tomography, and his serum carcinoembryonic antigen level was 116 ng/dL, his final diagnosis was a stage IVb urachal carcinoma. He received 11 courses of mFOLOX6, and underwent a laparoscopy-assisted partial cystectomy and pelvic lymph node dissection. Pathological examination confirmed negative surgical margins, but remained tumor cells were confirmed. The patient continued mFOLFOX6 treatment for 12 months postoperatively, with no disease progression observed.

A 35-year-old man visited a local doctor for continuing analysis of his infertility. Semen analysis revealed azoospermia while an ultrasonography detected a right testicular tumor with a diameter of 10 mm. A blood test was negative for tumor markers. Magnetic resonance imaging showed a 1-cm tumor in the right testis and atrophy of the left testis. A testicular tumor arising from a functional unilateral testis was discovered during infertility treatment for which the patient was referred to our hospital for fertility preservation. Right and left testicular volumes were 18 mL and 3 mL, respectively, and his serum testosterone level was 2.96 ng/mL. Noting the atrophy of the contralateral testicle, we proceeded with a rapid pathology diagnosis by partial testicular resection. If no evidence of tumor malignancy was found, the surgery would have been concluded with no further dissection. Since the patient was undergoing fertility treatment, the decision was made to take sperm from the extracted testicle to preserve his fertility, followed by orchiectomy. Because a seminoma was suspected through the rapid pathological diagnosis, the man eventually underwent higher orchiectomy and testicular sperm extraction. The final diagnosis was seminoma, followed by successful retrieval of a sufficient level of sperm. Post operative serum testosterone level was found to be 0.32 ng/mL, after which testosterone replacement therapy was introduced. Through rapid diagnosis of pathology, successful management and outcome were achieved in the case of testicular cancer combined with infertility.

A 70-years-old man with metastatic hormone-sensitive prostate cancer received the apalutamide, an oral androgen receptor signaling inhibitor. On day10 after drug initiation, fever and skin rash appeared on his whole-body surface. He stopped taking the drug on day18 and skin symptoms temporarily improved about 7 days after discontinuation. However, on day 38, symptoms recurred, and the patient was admitted to the hospital as an emergency due to suspicion of Stevens-Johnson syndrome. Steroid pulse therapy was administered, and gradual improvement of the skin lesions was observed. With the widespread use of apalutamide in daily clinical settings, severe drug eruptions such as the present case may potentially increase, and further additive experiences are awaited.

The patient was a male in his 60s who underwent a retroperitoneoscopic right nephrectomy for a diagnosis of right renal cell carcinoma (cT3aN0M0). During surgery, the patient was positioned in the left lateral recumbent, jackknife position. A blood test of the day after surgery showed an abnormally high CK level of 23,038 U/L. However, because his only symptom was mild pain in the left lower back, the patient was placed under follow-up observation. Two days postoperatively, the patient had worsening left lumbago, swelling, stiffness, and paresthesias in the left lumbar region. A simple CT scan showed internal hypo-absorption and increased volume of the left erector spinae muscle. With a diagnosis of left erector spinae compartment syndrome, the patient underwent an emergency decompressive fasciotomy by an orthopedic surgeon. The patient's postoperative course was uneventful with no sequelae, and he was discharged on postoperative day 22.In this case, the increased pressure on the lumbar region due to the cushion inserted into the lumbar flexion to reinforce the jackknife position was thought to have contributed significantly to the development of erector spinae compartment syndrome.Although erector spinae compartment syndrome is very rare after lateral recumbency surgery, taking thorough precautions is necessary, including the decompression of as much pressure as possible in the preoperative position and appropriate intraoperative blood pressure control, and to deal with it promptly, including fasciotomy in case of postoperative low back pain that coincides with the surface of the operating table.

A 14-year-old boy developed hydronephrosis and worsening renal function due to fibroepithelial polyps of the bladder and left ureter at the age of 12 years. The endoscopic treatment of ureteral polyps was attempted by his previous doctor; however urethral stricture and ureteral stricture developed and was untreatable. Therefore, he was referred to our hospital for further reconstructive treatment. He underwent Palminteri urethroplasty with penile skin graft for urethral stricture at the age of 13 years, followed by ureteroplasty at the age of 14 years. The stenotic ureter was minimally resected, with only complete obstruction and residual polyps, and augmented onlay ureteroplasty with a buccal mucosa graft was performed. Nephrostomy was removed 13 days after surgery, followed by the ureteral stent 4 months after surgery. Retrograde pyelography and ureteroscopy were performed 1 year and 2 years postoperatively, and neither recurrent strictures nor polyps were observed. The patient is doing well 3 years postoperatively.

(Objective) This study aimed at evaluating the efficacy and safety of upfront docetaxel (DTX) treatment and androgen deprivation therapy (ADT) in male patients with high-volume metastatic castration-sensitive prostate cancer (HV-mCSPC). (Methods) This retrospective study was conducted using the medical records of 30 patients treated for HV-mCSPC by using upfront DTX treatment along with ADT at Atsugi City Hospital between December 2015 and December 2022. The patient characteristics, demographics, oncological outcomes, adverse events, and sequential therapy were evaluated. (Results) Thirty patients were included in the final analysis. The median patient age and prostate-specific antigen at diagnosis were 73 years (range, 53-83 years) and 250 mg/ml (range, 0.54-3,817 ng/ml), respectively. The completion rate of six cycles of upfront DTX treatment was 86.7%. The median progression-free survival was 24 months; the median overall survival was not reached, and the 5-year survival rate was 71.5%. Alopecia was the most frequent non-hematological adverse event (60%) followed by fatigue (53.3%). Overall, adverse events of grade 3 or higher occurred in 46.7% of the patients, with neutropenia being the most frequent. The incidence of neutropenia of grade 3 or higher was significantly lower in the group receiving primary prophylaxis with long-acting granulocyte colony-stimulating factor (7.7% vs. 75%, P = 0.009). Abiraterone was the most frequently administered sequential treatment in 12 patients (60%). (Conclusion) In the triplet combination treatment era, upfront DTX treatment and ADT for patients with HV-mCSPC was safe as primary prophylaxis for severe neutropenia and effective as an upfront treatment. However, it should be selected if its effectiveness is superior to triplet treatment considering adverse events, cost-effectiveness, and quality of life.

(Objective) The study aimed to retrospectively evaluate the therapeutic effects of adjuvant chemotherapy (AC) in patients following radical cystectomy (RC) in locally advanced bladder cancer. (Methods) A single-center-derived database registered 227 patients diagnosed with muscle-invasive bladder cancer and treated with RC and pelvic lymphadenectomy between March 2003 and December 2021. Of these, patients diagnosed with non-organ-confined diseases were classified as either pT3-T4 or pN-positive without distant metastasis. Platinum-based AC was administered for the following categories: two courses for patients with pT3-T4 and pN-negative and three courses for those with pTany and pN-positive. The primary endpoint was the disease-free survival (DFS) and overall survival (OS) between the patients receiving and not receiving AC. (Results) Among all patients, 90 were diagnosed with non-organ-confined disease: 43 (47.8%) were treated with AC and the remaining 47 (52.2%) were left untreated. The methotrexate, vinblastine, doxorubicin, and cisplatin regimen; the gemcitabine and cisplatin regimen; and the gemcitabine and carboplatin regimen were administered to 14 (32.6%), 25 (58.1%), and 4 (9.3%) patients, respectively. With a median follow-up period of 26 months, the groups that received and did not receive AC had 2-year DFS rates of 36.3% and 25.9% (median DFS time: 15 vs. 8 months, p=0.026) and 2-year OS rates of 64.3% and 41.4% (median OS time: 38 vs. 18 months, p=0.064), respectively. In patients with pT3-T4 and pN-negative, no significant difference in the median DFS and OS between the AC and non-AC groups was observed. However, in patients with pTany and pN-positive, the DFS (median: 14 vs. 4.5 months, p=0.002) and OS (38 vs. 11.5 months, p=0.009) were longer in the AC than those in the non-AC group, respectively. The multivariate Cox regression analysis revealed that AC administration was an independent predictor for DFS (hazard ratio: 0.44, 95% confidence interval: 0.24-0.79, p=0.006). (Conclusion) Platinum-based AC following RC significantly improved DFS in pN-positive patients with locally advanced bladder cancer.

(Objective) We report the effectiveness of combination therapy with vibegron in pediatric patients with neurogenic bladder inadequately responding to anticholinergic agents. (Subjects and methods) This retrospective study involved 13 pediatric patients with neurogenic bladder treated with anticholinergics at our department from November 2019 to January 2021 who had an inadequate response and received combination therapy with vibegron. Changes in the volume of urinary incontinence before and after the use of vibegron reported during interviews from the 13 patients were compared. In addition, bladder capacity at the end of examination, bladder capacity at the end of examination/expected bladder capacity (EBC), and bladder compliance were compared using the Wilcoxon signed rank test in 9 patients for whom urodynamics (UDS) or video urodynamics (VUDS) was performed before and after introduction of vibegron. (Results) The 13 patients comprised 8 boys and 5 girls. The median age was 13 years (range, 5-18 years). Underlying diseases included 9 cases of spina bifida, 1 case of Hinman syndrome, 1 case of cervical vertebra injury, 1 case of idiopathic cervical epidural hematoma combined with spina bifida, and 1 case of spinal cord infarction. Eight of the 13 patients experienced decrease in urinary incontinence after the introduction of vibegron. All 9 patients who underwent UDS or VUDS before and after introduction of vibegron displayed significant differences in bladder capacity at the end of the examination, bladder capacity at the end of the examination/EBC, and bladder compliance, indicating improvement. (Conclusion) Combination therapy with vibegron is effective for pediatric patients with neurogenic bladder who have inadequately responded to anticholinergic agents.