Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study.

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.

Serum soluble B7-H3 is a prognostic marker for patients with non-muscle-invasive bladder cancer.

BACKGROUND: B7-H3 is a member of the B7 family of immune-regulatory ligands and is a costimulatory molecule promoting the T cell response in vitro. We herein investigated the clinical utility of serum soluble B7-H3 (sB7-H3) in patients with non-muscle invasive bladder cancer (NMIBC). METHODS: We analyzed 555 patients in whom NMIBC was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum sB7-H3 (sB7-H3) level using the enzyme-linked immunosorbent assay (ELISA) and evaluated the utility of sB7-H3 as a prognostic biomarker for NMIBC. We used the Cox proportional hazards regression model to assess recurrence-free survival (RFS) and progression-free survival (PFS) with the sB7-H3 level. RESULTS: We detected high levels of sB7-H3 in the sera of 47% of patients with NMIBC versus only 8% in healthy donors. The increase of sB7-H3 was significantly associated with poor RFS and PFS. Multivariate analysis showed that elevated sB7-H3 was an independent prognostic factor of RFS and PFS. According to the European Organization for Research and Treatment of Cancer (EORTC), in intermediate-low and intermediate-high risk groups, the presence of sB7-H3 significantly determined the rate of recurrence and progression. CONCLUSIONS: Our data suggested that evaluating serum sB7-H3 expression is a useful tool for predicting the prognosis of patients with NMIBC.

Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma.

BACKGROUND: B7-H4 is a member of the B7 family of immune-regulatory ligands and is considered to be a negative regulator of the immune response. We investigated the clinical significance of serum soluble B7-H4 in patients with non-metastatic clear cell renal cell carcinoma. METHODS: We analyzed 108 patients in whom non-metastatic clear cell renal cancer was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum soluble B7-H4 level using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and evaluated the association between the peripheral blood neutrophil count and sB7-H4 as well as the utility of soluble B7-H4 as a prognostic biomarker for clear cell renal cancer. The Cox proportional hazards regression model was used to assess the PFS and OS with the soluble B7-H4 level. RESULTS: We detected high levels of soluble B7-H4 in the sera of 56% of patients with non-metastatic clear cell renal cell carcinoma versus only 10% of healthy donors. Elevated soluble B7-H4 levels were associated with changes in an elevated peripheral blood neutrophil count. The increase of soluble B7-H4 also was significantly associated with poor PFS and OS. Multivariate analysis showed that the elevation of the soluble B7-H4 level was an independent prognostic factor for PFS and OS. CONCLUSIONS: Our data suggest that the association between serum soluble B7-H4 and peripheral blood neutrophil count, as well as the evaluation of serum soluble B7-H4 expression is a useful tool for predicting the prognosis of patients with non-metastatic clear cell renal cell carcinoma.

Drug review: Pazopanib.

Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -ß, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma. The importance of pazopanib has been acknowledged, with positive results demonstrated in large-scale clinical trials involving patients with soft-tissue sarcoma and renal cell carcinoma. However, adverse events such as liver dysfunction and hypertension are common, often necessitating treatment discontinuation. These adverse events are generally manageable, and from the perspective of health-related quality of life and cost-effectiveness, pazopanib provides an improvement in quality-adjusted life years and decreases the treatment cost compared with other alternatives. In this review, we present the results of clinical trials and discuss the pharmacological action of pazopanib, with the aim of evaluating its current state by examining various associated issues.

Effect of dutasteride on castration-resistant prostate cancer.

It has previously been demonstrated that the intratumoral generation of the potent androgen dihydrotestosterone (DHT), contributes critically to the progression of prostate cancer and its castration-resistant form, castration-resistant prostate cancer (CRPC). Circulating testosterone is converted into DHT by 5α-reductase (SRD5A). Dutasteride is a dual inhibitor of type I and II SRD5A. The present study assessed the effectiveness of dutasteride in the treatment of CRPC. Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center. Following diagnosis, the patients received 0.5 mg dutasteride daily. The patients' median age was 77.3 years (range, 63-90). Bone metastases were recognized in 12 patients. All the patients received dexamethasone. Twenty-four (59%) patients had previously undergone chemotherapy, while 11 (27%) received docetaxel, and 24 (59%) estramustine. The prostatic-specific antigen (PSA) level declined in 17 (41%) patients from the baseline value, following dutasteride treatment. The median value for the PSA decrease was 23% (range, 4.3-89.8%), and the median duration of the response was 4 months (range, 1-10). The PSA response rate (defined as >50% decline in PSA from the baseline value) was recognized in 7 (17%) patients. The median duration of the response was 3 months (range, 2-10). Dutasteride was efficacious against CRPC in certain patients and may be a promising option in CRPC treatment. A prospective randomized trial is necessary to verify the efficacy of dutasteride.

The safety and effect of chemotherapy with short hydration for urothelial cancer on patients' quality of life.

OBJECTIVE: Our aim was 2-fold: first, to assess the safety of short hydration treatment for urothelial cancer; and second, to assess the resultant quality of life of patients who received the treatment. METHODS: We assessed 61 patients including 31 outpatients and 30 inpatients, who received a combination of gemcitabine and cisplatin chemotherapy with short hydration. The serum creatinine (Cr) level and the estimated glomerular filtration rate were measured to assess renal function using linear mixed model analysis. To assess quality of life, the patients were asked to respond to the Functional Assessment of Cancer Therapy-General questionnaire. The responses were then analyzed using the paired t-test. RESULTS: Patients who received short hydration chemotherapy showed no significant change in serum Cr level (P = 0.423) or estimated glomerular filtration rate  (P = 0.582). There was also no significant change in serum Cr level or estimated glomerular filtration rate between patients who received short hydration chemotherapy and those who received consecutive hydration chemotherapy (P = 0.154 and 0.311, respectively). In every patient, the Functional Assessment of Cancer Therapy-General total score and subscale scores both improved as a result of outpatient chemotherapy with short hydration (P < 0.01). CONCLUSIONS: The short hydration gemcitabine and cisplatin regimen for patients with urothelial cancer was safe. Further, the outpatient chemotherapy was found not only to be safe, but also to have improved the patients' quality of life.

METASTATIC SMALL CELL CARCINOMA OF THE URINARY BLADDER TREATED WITH SYSTEMIC CHEMOTHERAPY INCLUDING AN AMRUBICIN; A CASE REPORT.

We report a 59-year-old male patient with metastatic small cell carcinoma of the bladder treated with systemic chemotherapy including an amrubicin. The patient was referred to our hospital complaining of macrohematuria. A cytoscopy revealed a non-papillary, broad-based tumor extending from the right to the posterior wall of the bladder. A computed tomography showed bilateral hydronephrosis caused by the bladder tumor and multiple metastases to the para-aortic and common iliac lymph nodes. The histopathological findings following a transurethral resection of the bladder tumor revealed a T2N3M1, LYM, stage IV small cell carcinoma. We administered two courses of systemic chemotherapy consisting of cisplatin (CDDP) plus an etoposide (VP-16), a first-line treatment usually administered to patients with small cell carcinoma of the lung. We then administered second-line chemotherapy consisting of CDDP plus an irinotecan. When the first and second-line therapies failed to halt progression of the disease, we decided to use amrubicin as the third-line therapy concomitant with radiotherapy for local control. Although the NSE (neuron-specific enolase) value decreased, the patient died 11 months after the initial examination. To our knowledge, this is the first case in which small cell carcinoma of the bladder was treated with amrubicin.

Preoperative neutrophil-lymphocyte ratio as an independent prognostic marker for patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To predict the prognosis, we evaluated the significance of the preoperative neutrophil-lymphocyte ratio (NLR) in patients with upper urinary tract urothelial carcinoma (UUTUC). PATIENTS AND METHODS: A cohort of 137 patients diagnosed with UUTUC from 1994 to 2008 at Tokyo Metropolitan Tama Medical Center was enrolled in this retrospective study. Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: On univariate analysis, pathologic T stage, grade, lymphovascular invasion, C-reactive protein (CRP) level, and NLR were significantly associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). The RFS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 74.3% and 30.4%, respectively. The CSS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 81.3% and 29.4%, respectively. The multivariate Cox proportional hazards regression models showed that the NLR could be an independent predictor for RFS and CSS. Based on the results of multivariate analysis, the scoring model was developed. RFS and CSS rates at 5 years were as follows: 0 risk factor, 97.1% and 97.0%, respectively; 1 risk factor, 91.1% and 90.9%, respectively; 2 risk factors, 39.5% and 58.6%, respectively; 3 risk factors, 26.6% and 28.6%, respectively; and 4 risk factors, 6.0% and 5.6%, respectively. CONCLUSIONS: The preoperative NLR is an independent prognostic predictor. The model based on the NLR and pathologic factors can be useful in clinical practice.

Metastatic renal cell carcinoma change vascularity.

Several molecular targeted agents have been approved for clinical use for metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC is presented. These tumors could change vascularity by administration of molecular agents. We could select a drug timely based on findings of computed tomography. To our knowledge, this is the first report that tumor's character change induced by molecular targeted agents can be detected and the efficacy of molecular targeted agents can be predicted.