Favorable Response of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma with Only Small Lesions to not be Considered Measurable by RECIST.

PURPOSE: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported. MATERIALS AND METHODS: The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions. RESULTS: The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012). CONCLUSION: We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.

Blood Cell Count Biomarkers Predicting Efficacy of Pembrolizumab as Second-line Therapy for Advanced Urothelial Carcinoma.

BACKGROUND/AIM: To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS: This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS: Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR <2.9 and 1-month change NLR <+43% groups had a significantly better OS than the pretreatment NLR ≥2.9 and 1-month-change NLR ≥+43% groups. CONCLUSION: NLR, MLR, PLR and SIRI before pembrolizumab and 1-month-change NLR in advanced UC correlated with OS after pembrolizumab treatment.

Efficacy of androgen deprivation therapy for localized prostate cancer: analysis of pT0 evaluated by radical prostatectomy specimen.

AIM: In order to investigate which types of localized prostate cancer can be treated most effectively by androgen deprivation therapy (ADT), cases of no residual cancer in radical prostatectomy specimens (pT0) after neoadjuvant ADT were analyzed. PATIENTS AND METHODS: Patients with localized prostate cancer who underwent radical prostatectomy after neoadjuvant ADT were investigated retrospectively. RESULTS: Thirty-two patients (24.2%) were diagnosed with pT0 disease by pathological evaluation. The positive-core proportion of prostate biopsy was lower, the duration of neoadjuvant ADT was longer, and prostate-specific antigen (PSA) nadir before radical prostatectomy was lower in pT0 cases compared to non-pT0 cases, and these differences were statistically significant. The percentage of pT0 cases with PSA nadir <0.2 ng/ml and <0.008 ng/ml before radical prostatectomy were 29.2% (21 out of 72 cases) and 83.3% (5 out of 6 cases), respectively. The positive-core proportion of prostate biopsy and PSA nadir before radical prostatectomy had a significant impact on pT0 status after neoadjuvant ADT. CONCLUSION: ADT for localized prostate cancer is thought to be highly effective in cases with low cancer volume. ADT is effective in cases of localized prostate cancer with PSA below the levels of detection by supersensitive PSA assay, and such cases show no cancer recurrence. Treatment options in such cases include intermittent or discontinuation of ADT.

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells.

AIM: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. METHODS: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. RESULTS: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. CONCLUSIONS: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.