Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study.

Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Efficacy and safety of pembrolizumab for older patients with chemoresistant urothelial carcinoma assessed using propensity score matching.

BACKGROUND: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC). METHODS: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared. RESULTS: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651). CONCLUSIONS: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.

[Multi-institute survey on actual conditions of urologic management for severe bladder dysfunction after hysterectomy].

We conducted a multi-institute survey on the conditions related to urologic management of severe voiding dysfunction after hysterectomy for uterine cancer with or without postoperative irradiation. Our first study population was a group of adult female patients currently managed by urologists, using clean intermittent catheterization (CIC). Of the 287 patients in this group, 99 (34%) had suffered from uterine cancer. Of these patients, 94 underwent hysterectomy for this disease; 44 and 30 were treated with or without postoperative radiation, respectively, while postoperative irradiation status was unknown for 20. Median follow-up after surgery was 21 (0.2-52) years and median interval from operation to the introduction of CIC was 4.0 (0-49) years. CIC tended to be introduced later for patients with postoperative radiation than those without it. Seventy-four patients, who required invasive urologic interventions other than CIC for voiding dysfunction after hysterectomy, are the second study population. Most of these (82%) had received postoperative irradiation. Continuous Foley catheter placement was the most frequent procedure. Long-term follow-up and urologic management for voiding dysfunction is required for patients undergoing hysterectomy.

[BK virus nephropathy in a kidney transplant recipient: a case report and literature review].

BK virus nephropathy (BKVN) has emerged as an important cause of allograft dysfunction and loss in kidney transplant recipients. We present a case in a 30-year-old female who underwent ABO-compatible living kidney transplant from her mother and was maintained with tacrolimus, mycophenolate mofetil and prednisolone. The serum creatinine level was stabilized about 0.9 mg/dl on postoperative day (POD) 35. On POD258, the serum creatinine increased to 1.8 mg/dl and the patient received methylpredonisolone pulse therapy under the diagnosis of acute rejection, which resulted in further increase in creatinine level from 1.8 to 2.6 mg/dl. Urine cytology showed decoy cells, but renal biopsy specimen showed no evidence of viral infection. Despite histopathological findings, positive urine and serum BKV-DNA suggested that allograft dysfunction was caused by BKVN. Therefore, the immunosuppession was reduced and gamma-globuline was given for 2 weeks. After the treatment, urine cytology became negative for decoy cells and serum creatinine level recovered to 2.0 mg/dl. On POD456, serum creatinine level was stabilized about 1.8 mg/dl and decoy cells remained negative.

[The influence over the long-term prognosis of BCG therapy and the surgical treatment in superficial bladder cancer treatment].

From the view point that total cystectomy is important in treatment of carcinoma in situ (CIS) of the bladder, we reviewed the cases showing resistance to bacillus Calmette-Guerin (BCG) among 42 CIS treated with intravesical BCG. Twenty-six cases were cured by BCG treatment. Twelve total cystectomies were done in 16 cases of BCG-resistant CIS of the bladder. Four died with urethral invasion or upper urinary tract recurrence. There was invasion into the prostate in 3 cases. The development of CIS to the upper urinary tract and the prostatic urethra is not rare and this has an influence on the prognosis. In bladder CIS treatment, the inspection to see extravesical progression is necessary. It is important not to delay the radical cystectomy.

[Vesical actinomycosis: a case report].

A 55-year-old woman had complained of lower abdominal pain for 5 years. A computed tomographic CT scan and magnetic resonance imaging revealed a heterogeneous density mass on the left side of the bladder. CT-guided needle biopsy showed only inflammatory cell infiltration without histological diagnosis. To confirm the diagnosis, the mass was resected together with part of the bladder and peritoneum. On the cut surface, the mass was centrally pale yellow and adherent to the thickened hard wall of the bladder and peritoneum. Pathological diagnosis was chronic granulomatous inflammation with actinomycosis. This is, to our knowledge, the 12th case report of vesical actinomycosis in Japan. Although actinomycosis is very rare in urological field, abdominal actinomycosis should be considered as the differential diagnosis of any inflammatory abdominal mass.

[Adult sacrococcygeal teratoma: a case report].

We report a case of adult sacrococcygeal teratoma resected by an abdominosacral approach. A cystic mass 13 cm in diameter in the pelvic cavity and left hydronephrosis were detected incidentally by abdominal computed tomographic (CT) scan in a 55-year-old man. The pelvic tumor extending from the presacral area to the coccyx was resected via a combined abdominal and transsacral approach. The resected specimen weighed 700 g and the pathological diagnosis was mature teratoma. While the sacrococcygeal area is the most frequent site of teratoma in infants, it is a rare site in adults. This is to our knowledge, the 30th case report of adult sacrococcygeal teratoma in Japan. At one month after the operation the patient had no bowel dysfunction and no dysbasia, but he had mild bladder dysfunction requiring self-catheterization twice a day at twelve months. The patient had no evidence of disease at twenty months after the operation.

[Transitional cell carcinoma in prostate after intravesical instillation of Bacillus Calmette-Guerin].

We report 3 cases of prostatic involvement of transitional cell carcinomas (TCCs). All cases presented positive urinary cytology after intravesical instillation of Bacillus Calmette-Guerin (BCG) and then random biopsy of bladder and transurethral resection (TUR)-biopsy of prostatic urethra were performed. TUR-biopsy demonstrated TCC in the prostate, although random biopsy failed to detect tumors in the bladder in all cases. Case 1 was treated with cystourethrectomy with ileal conduit, case 2 was treated with cystourethrectomy with bilateral ureterocutaneostomy and case 3 was treated with cystectomy with orthotopic ileal neobladder reconstruction. All cases are alive with no evidence of disease. TUR-biopsy of prostatic urethra should be perfomed when patients present positive urinary cytology after BCG instillation therapy, because prostatic involvement of TCC associated with bladder carcinoma in situ is not rare.

Epithelial stromal tumor of the seminal vesicle.

Primary tumors of the seminal vesicles are rare neoplasms; there have been only 69 accepted cases. The histologic features are usually adenocarcinoma; however, there are rarely reported epithelial stromal tumors of the seminal vesicles. We report a case of a 70-year-old man with an epithelial stromal tumor of the seminal vesicle who presented without symptoms of bladder outlet obstruction. The patient underwent radical cystoprostatectomy. No signs of tumor recurrence were noted within 14 months of surgery. To our knowledge, 13 cases of epithelial stromal tumors of the seminal vesicle have been previously reported.