Sachiyo Murai

Outcome of Metastasectomy for Urothelial Carcinoma: A Multi-Institutional Retrospective Study in Japan

PURPOSE We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. MATERIALS AND METHODS A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. RESULTS Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19-80) from the initiation of treatment for metastases and 26 months (IQR 11-90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). CONCLUSIONS Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis.

Comparison of 90-day complications between ileal conduit and neobladder reconstruction after radical cystectomy: A retrospective multi-institutional study in Japan

To determine the differences in the type, incidence, and severity of 90‐day morbidity after radical cystectomy between two different methods of urinary diversion, ileal conduit and neobladder.

RENAL nephrometry score is a predictive factor for the annual growth rate of renal mass.

To evaluate the association between the RENAL nephrometry score and annual growth rates of renal masses presumed to be renal cell carcinoma.

Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma

BackgroundTo clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci.MethodsThe present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated.ResultsA total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm3 tumors increased according to the upgrade of Likert scores (score 1 or 2: 33 %; score 3: 68.8 %; score 4 or 5: 90.9 %, χ2 test, p < 0.0001). The proportion with a Gleason score >7 also increased from scale 2 to scale 5 (scale 2: 0 %; scale 3: 56.3 %; scale 4: 72.7 %; 5: 90.9 %, χ2 test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm3 (<0.2 cm3: 10.3 %; 0.2-0.5 cm3: 25 %; 0.5-1.0 cm3: 66.7 %; 1.0 < cm3: 92.1 %).ConclusionsEach Likert scale favobably reflected the corresponding tumor’s volume and Gleason score. Our observations show that “score 3 or higher” could be a useful threshold to predict clinically significant carcinoma when considering treatment options.

Prognosis of Japanese patients with previously untreated metastatic renal cell carcinoma in the era of molecular‐targeted therapy

A multicenter cooperative study was conducted to clarify the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular‐targeted therapy and the clinical usefulness of the Japanese metastatic renal cancer (JMRC) prognostic classification. Of 389 consecutive patients for whom treatment was started between 2008 and 2010 at 23 hospitals in Japan, 357 patients who received vascular endothelial growth factor receptor‐tyrosine kinase inhibitor (VEGFR‐TKI) or cytokine as initial systemic therapy were the subject of the present study. Patients were classified into three prognostic groups according to the JMRC prognostic classification. The endpoints were progression‐free survival (PFS) and overall survival (OS) after the start of the initial treatment. The median PFS and OS for the entire cohort of 357 patients were 9.1 and 27.2 months, respectively. VEGFR‐TKI were selected for patients with multiple organ metastases, those with liver metastasis, and those with bone metastasis. The median PFS and OS were 11.0 and 23.2 months and 5.4 and 38.2 months in the VEGFR‐TKI group and the cytokines group, respectively. The JMRC prognostic classification was useful as a prognostic model for PFS and OS (c‐indexes: 0.613 and 0.630 in patients who initially received VEGFR‐TKI and 0.647 and 0.642 in patients who received cytokines, respectively). The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular‐targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model.

A Multi-Center International Study Assessing the Impact of Differences in Baseline Characteristics and Perioperative Care Following Radical Cystectomy.

Background: To identify potential avenues for quality improvement, we compared the variations in clinical practice and their association with perioperative morbidity and mortality following radical cystectomy (RC) for bladder cancer in the United States (US) and Japan. Methods: We reviewed our retrospectively collected database of 2240 patients who underwent RC for bladder cancer at the University of Michigan (n = 1427) and in 21 Japanese institutions (n = 813) between 1997 and 2014. We performed a systematic comparison of clinical and perioperative factors and assessed predictors of perioperative morbidity and mortality. Death within 90 days of surgery was the primary outcome. Results: There were apparent differences between the two study populations. Notably, US patients had a significantly greater BMI and higher ASA score. In Japanese institutions, median postoperative hospital stay was significantly higher (40 days vs. 7 days, p <  0.001) and 90-day readmission rates were significantly lower (0.6% vs. 26.8% , p <  0.001). There was a total of 1372/2240 (61.2%) patients with complications within 90 days and 66/2240 (2.9%) patient deaths. Significant predictors of 90-day mortality were older age (OR 1.04, CI 1.01–1.07), higher body mass index (OR 1.07, CI 1.02–1.12), node-positive disease (OR 3.14, CI 1.78–5.47), increased blood loss (OR 1.02, CI 1.01–1.03), and major (Clavien-grade 3 or greater) complication (OR 3.29, CI 1.88–5.71). Conclusion: Despite major differences in baseline characteristics and care of cystectomy patients between the two study populations, peri-operative mortality rates proved to be comparable. This data supports an exploration of non-traditional factors that may influence mortality after cystectomy.

Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis

OBJECTIVE To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. METHODS A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. RESULTS The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. CONCLUSIONS We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.

Outcome of metastatic urothelial carcinoma treated by systemic chemotherapy: Prognostic factors based on real-world clinical practice in Japan

AIM To clarify prognostic factors of metatstatic urothelial carcinoma treated by systemic chemotherapy in real-world clinical practice in the Japanese population. MATERIALS AND METHODS A total of 228 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in the present multi-institutional study. The gemcitabine plus cisplatin regimen was administered as first-line chemotherapy to 131 patients, whereas methotrexate, vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71 patients. Of the 228 patients, 119 received at least 2 different regimens and 22 underwent resection of metastases (metastasectomy). Multivariate survival analysis was performed using the Cox proportional hazards model. The characteristics included were age, sex, Eastern Cooperative Oncology Group performance status (PS), primary site, pathology of primary site, hemoglobin levels, lactate dehydrogenase levels, C-reactive protein levels, corrected calcium levels, estimated glomerular filtration rate levels, history of prior chemotherapy, metastatic sites, resection of primary site, number of metastatic organs, and metastasectomy. RESULTS The median overall survival (OS) time was 17 months. On multivariate analysis, female sex, good Eastern Cooperative Oncology Group PS at presentation, hemoglobin level≥10g/dl, and single organ metastasis were significant independent predictors of prolonged OS. For the survival effect of metastasectomy, the median OS time of the 22 patients with metastasectomy was 53 months, which was significantly longer when compared with patients not undergoing metastasectomy (15mo). After adjustment for the 4 aforementioned prognostic factors, metastasectomy still remained significant (hazard ratio: 0.364, P = 0.0008). CONCLUSIONS Female sex, more favorable PS at presentation, hemoglobin level>10g/dl, and single organ metastasis were favorable prognostic factors. In addition, metastasectomy was associated with long-term disease control.

Comparative study of lymph node dissection, and oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection

We revealed the feasibility of lymph node dissection (LND) with a laparoscopic approach and the equivalent oncological outcome of laparoscopic nephroureterectomy compared with open nephroureterectomy when regional LND is performed.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan

We revealed prognostic factors in metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Performance status, C-reactive protein level and response to prior chemotherapy were prognostic indicators.