Potential therapeutic effects of adjuvant chemotherapy after neoadjuvant chemotherapy for locally advanced muscle-invasive bladder cancer.

BACKGROUND: Although the administration of neoadjuvant chemotherapy has been associated with improved prognosis in patients with muscle-invasive bladder cancer, the therapeutic effects of adjuvant chemotherapy remain unknown in real-world settings. Therefore, we herein evaluated the clinical outcomes of adjuvant chemotherapy in pT3/4 muscle-invasive bladder cancer patients. MATERIALS AND METHODS: Among 587 bladder cancer patients who underwent radical cystectomy, 200 with a pathological T3 or higher muscle-invasive bladder cancer were included in the present analysis. Recurrence-free survival and cancer-specific survival were assessed by multivariate Cox regression analysis. RESULTS: Median age was 73 years, and the median follow-up duration was 17 months. The 5-year cancer-specific survival rate was 53.6% in 66 patients treated with adjuvant chemotherapy, which was significantly higher than that in those without adjuvant chemotherapy (34.0%, P = 0.025). The absence of adjuvant chemotherapy (hazard ratio = 2.114, P = 0.004) and lymphovascular invasion (hazard ratio = 2.203, P = 0.011) was identified as independent prognostic indicators for cancer-specific death. In patients treated without neoadjuvant chemotherapy (n = 143), the absence of adjuvant chemotherapy (hazard ratio:1.887, P = 0.030) remained an independent indicator for cancer-specific death. For those treated with adjuvant chemotherapy without neoadjuvant chemotherapy, three or more adjuvant chemotherapy cycles were independently associated with favourable outcome (hazard ratio = 0.240, P = 0.009). In contrast, for neoadjuvant chemotherapy-treated patients (N = 57), adjuvant chemotherapy was not independently associated with disease recurrence or cancer-specific death. CONCLUSION: Adjuvant chemotherapy was associated with improvements in the prognosis of patients, even in those with pT3 or higher muscle-invasive bladder cancer. Although three or more cycles of adjuvant chemotherapy were effective for muscle-invasive bladder cancer patients treated without neoadjuvant chemotherapy, no therapeutic advantages were observed with additional adjuvant chemotherapy in patients treated with neoadjuvant chemotherapy.

Significance of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer.

BACKGROUND: Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy. METHODS: We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group). RESULTS: No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007). CONCLUSIONS: Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.

Oncological outcomes of dose reductions in cisplatin due to renal dysfunction for patients with metastatic urothelial carcinoma.

Objective: To investigate whether dose reductions in cisplatin due to renal dysfunction were associated with worse clinical outcomes in metastatic urothelial carcinoma (UC) patients. Patients and methods: One hundred and fifty one metastatic UC patients who received first-line gemcitabine plus cisplatin (GC) salvage chemotherapy without a previous history of peri-surgical chemotherapy were included in this retrospective study. Patients with endogenous creatinine clearance of 60 mL/min or more were treated with a full dose of cisplatin, while those with 45-59 and 30-44 mL/min were treated with 75% and 50% doses, respectively. Patients were divided into three groups based on the average administered dose of cisplatin of 100% (Group A, N = 43), 99%-75% (Group B, N = 59), and less than 75% (Group C, N = 49), and therapeutic responses and the toxicity of GC were compared. Results: Complete response rates were 9.3%, 13.6%, and 14.3% in groups A, B, and C, respectively. One-year progression-free survival rates were 22.9%, 31.1%, and 36.7% in groups A, B, and C with no significant differences. One-year cancer-specific survival rates were 56.1%, 71.1%, and 68.3% in groups A, B, and C with no significant differences. A multivariate Cox's regression analysis showed that the dose of cisplatin was not an independent prognostic factor for disease progression and cancer death. Furthermore, there were no significant differences in the incidence of severe adverse events. Conclusions: Dose reductions in cisplatin due to renal dysfunction did not worsen clinical outcomes for metastatic UC.

Extraperitoneal approach induces postoperative inguinal hernia compared with transperitoneal approach after laparoscopic radical prostatectomy.

OBJECTIVE: The aim of this study was to determine the incidence and risk factors of postoperative inguinal hernia and to investigate whether the difference of approach could induce postoperative inguinal hernia after laparoscopic radical prostatectomy. METHODS: We reviewed 493 consecutive patients who underwent laparoscopic radical prostatectomy from November 2000 to November 2007, and evaluated various preoperative parameters, specifically age, prostate-specific antigen (ng/ml), body mass index (kg/m(2)), prostate volume (ml), previous major abdominal surgery, previous appendectomy, previous inguinal hernia repair and laparoscopic approach as risk factors for postoperative inguinal hernia. RESULTS: Inguinal hernia occurred in 4 (4.9%) of the 81 patients in the transperitoneal approach group, and in 37 (9.0%) of the 412 patients in the extraperitoneal approach group. The overall incidence of inguinal hernia was 8.3% (41 of 493 patients). The median inguinal hernia-free survival time was 35 months and 6 months in the transperitoneal approach and extraperitoneal approach groups, respectively. Inguinal hernia developed within 2 years after surgery in 2 (50%) of 4 patients in the transperitoneal approach group, in 34 (91.9%) of 37 patients in the extraperitoneal approach group, for a total of 36 (87.8%) of 41 patients overall. Multivariate analysis showed that the extraperitoneal approach was a significant risk factor (P = 0.043) for inguinal hernia. CONCLUSIONS: Inguinal hernia is a frequent complication after laparoscopic radical prostatectomy, and the incidence of inguinal hernia is greater with the extraperitoneal approach than with the transperitoneal approach.

The clinical significance of urine cytology after a radical cystectomy for urothelial cancer.

OBJECTIVES: To evaluate the impact of urine cytology on the prediction of the upper urinary tract recurrence (UTR) of urothelial cancer after a radical cystectomy (RC) with urinary diversion. METHODS: A total of 125 patients who underwent RC from 1987 to 2005 were retrospectively identified. The median follow-up period was 64 months. The specimens for urine cytology were obtained from the urine voided or obtained through a catheter or a conduit. The relationship between a positive urine cytology result and UTR detection was determined. RESULTS: UTR was diagnosed in eight patients (6.4%) at a median follow-up of 63.3 months. The overall rate of a positive urine cytology result was 12.3% for the urine in an ileal conduit, 18.8% in a continental reservoir and 10.5% in an orthotopic neobladder. The overall sensitivity and specificity of the urine cytology for the detection of UTR were 75.0% and 90.6%, respectively. However, UTR could be diagnosed earlier by using urinary cytology, rather than by radiological examinations and/or related symptoms in only 5.9% (1/17 positive urine cytology) of cases. Eleven (64.7%) of 17 patients with positive urine cytology were false positive and eight (72.7%) of the 11 patients with no UTR had a positive urine cytology result only once. CONCLUSIONS: Urine cytology after RC was not a potent screening tool for the early detection of UTR because of the difficulty in distinguishing the cancer cells from degenerated intestinal epithelial cells in the urinary diversion urine.

The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients.

PURPOSE: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. METHODS: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). CONCLUSIONS: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

PURPOSE: To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. PATIENTS AND METHODS: A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). RESULTS: The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. CONCLUSION: MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy.

Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy.

Although the clinical utility of a frozen section analysis (FSA) at the time of radical cystectomy (RC) has already been established, its significance and utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have not yet been fully evaluated. We identified 458 patients (937 ureters) who underwent open RC for bladder cancer at our 7 Japanese institutions between 2004 and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients. FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity, specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139 (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively. In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111 out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters, and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%, respectively. No correlation was observed between preoperative clinical factors and FSA positivity in the NAC group; however, in the non-NAC group, the incidence of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT specimens was 8/41 (19.5%), which was significantly higher than that in their counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management of bladder cancer patients, the performance of FSA does not change and FSA at the time of RC may provide useful diagnostic information.

The prognostic significance of OCT4 expression in patients with prostate cancer.

Accumulating evidence suggests that OCT4 participates in tumorigenicity and malignancy in human cancers. However, the prognostic significance of OCT4 expression in prostate cancer (PCa) or predictive significance of OCT4 in docetaxel sensitivity in castration-resistant prostate cancer (CRPC) remains unclear. The aim of this study was to assess the prognostic value of OCT4 expression in PCa. We retrospectively analyzed the clinical records and evaluated the OCT4 expression in 205 patients with PCa who underwent radical prostatectomy. We examined the change of OCT4 expression in 3 patients with CRPC who underwent transurethral resection for local progression before and after docetaxel chemotherapy. OCT4 expression was significantly associated with higher pathological T stage (P < .001). The 5-year prostate-specific antigen recurrence-free survival rate was 56.8% in patients with higher OCT4 expression and 90.6% in patients with lower OCT4 expression (P < .001). Multivariate analysis revealed that high OCT4 expression was an independent prognostic indicator of prostate-specific antigen recurrence (P < .001). Elevated strong OCT4 expression in residual CRPC cells after docetaxel chemotherapy was observed in all CRPC patients, compared with before chemotherapy in corresponding specimens. Higher OCT4 expression represents a clinically relevant predictor of patient prognosis in PCa and may be a new biomarker that will provide additional prognostic information in CRPC when treated with docetaxel.

Ureteral metastasis from prostate cancer.

A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.

Difficulty in the intravesical morcellation procedure for leiomyoma of the prostate enucleated by HoLEP.

Leiomyoma of prostate are rare benign neoplasms that are usually diagnosed incidentally through postoperative pathological examination. A 70-year-old man is presented with severe symptoms of lower urinary tract obstruction. Although a digital rectal examination and the prostate-specific antigen level did not suggest malignancy, transrectal ultrasonography showed an unusual homogenous echoic mass measuring 45×37 mm in size in the prostate. A needle biopsy was performed and pathological diagnosis was prostatic leiomyoma. Holmium laser enucleation of prostate (HoLEP) was chosen and performed to resect the tumour. Although the enucleation step presented no problems, the morcellation procedure using a conventional transurethral mechanical morcellator was very difficult owing to the firmness of the tissue. By using a bipolar erectrosurgical loop, fragmentation and removal of tissue was accomplished. This is the first case reported of these rare neoplasms in which HoLEP was offered as a less invasive surgical approach. We emphasise the firmness of the leiomyomatous tissue, which would lead to morcellation failure.

Primary intratesticular leiomyosarcoma.

This report presents a case of primary intratesticular leiomyosarcoma. A 73-year-old male presented with a 6-year history of left scrotal swelling. A radiological examination revealed a left testicular tumour with multiple metastases in the lung, para-aortic lymph node and other organs. A radical orchiectomy was carried out and the pathology revealed an intratesticular leiomyosarcoma. The patient received additional chemotherapy. Cases of primary intratesticular leiomyosarcoma are rare. This is, to the best of our knowledge, only the tenth case of leiomyisaocoma in an adult reported in the literature, and the first case involving multiple metastases.