Hiromichi Iwamura

Oncological outcomes of neoadjuvant chemotherapy in patients with locally advanced upper tract urothelial carcinoma: a multicenter study

Objective The clinical impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. We investigated the oncological outcomes of platinum-based NAC for locally advanced UTUC. Results Of 234 patients, 101 received NAC (NAC group) and 133 did not (Control [Ctrl] group). The regimens in the NAC group included gemcitabine and carboplatin (75%), and gemcitabine and cisplatin (21%). Pathological downstagings of the primary tumor and lymphovascular invasion were significantly improved in the NAC than in the Ctrl groups. NAC for locally advanced UTUC significantly prolonged recurrence-free and cancer-specific survival. Multivariate Cox regression analysis using an inverse probability of treatment weighted (IPTW) method showed that NAC was selected as an independent predictor for prolonged recurrence-free and cancer-specific survival. However, the influence of NAC on overall survival was not statistically significant. Materials and Methods A total of 426 patients who underwent radical nephroureterectomy at five medical centers between January 1995 and April 2017 were examined retrospectively. Of the 426 patients, 234 were treated for a high-risk disease (stages cT3–4 or locally advanced [cN+] disease) with or without NAC. NAC regimens were selected based on eligibility of cisplatin. We retrospectively evaluated post-therapy pathological downstaging, lymphovascular invasion, and prognosis stratified by NAC use. Multivariate Cox regression analysis was performed for independent factors for prognosis. Conclusions Platinum-based NAC for locally advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed to clarify the clinical benefit of NAC for locally advanced UTUC.

Platinum-based Neoadjuvant Chemotherapy Improves Oncological Outcomes in Patients with Locally Advanced Upper Tract Urothelial Carcinoma

BACKGROUND Neoadjuvant chemotherapy (NAC) use for patients with locally advanced upper tract urothelial carcinoma (UTUC) is debatable. OBJECTIVE To investigate the efficacy and safety of platinum-based NAC for locally advanced UTUC. DESIGN, SETTINGS, AND PARTICIPANTS Of 233 consecutive patients who underwent radical nephroureterectomy, 55 patients received NAC (NAC group) and 138 patients did not (Ctrl group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two arms (Ctrl vs NAC) were matched using propensity scores to minimize selection bias. We retrospectively evaluated tumor response, post-therapy pathological downstaging, lymphovascular invasion, Ki67 status, and prognosis between pair-matched patients. Multivariate Cox regression analysis was performed for independent factors for prognosis. RESULTS AND LIMITATIONS We selected 51 pair-matched patients in each group. The regimens in the NAC group included gemcitabine and carboplatin, and gemcitabine and cisplatin. The median response rate in the NAC group was 28%. NAC-related adverse events were tolerable. Pathological downstaging of the primary tumor was significantly higher in the NAC group than in the Ctrl group. The MIB1 index (immunostaining for Ki67) was significantly higher in the NAC group. NAC for locally advanced UTUC significantly prolonged progression-free, cancer-specific, and overall survival. Multivariate Cox regression analysis using an inverse probability of treatment weighting method showed that NAC was selected as an independent predictor for prolonged cancer-specific survival. Limitations are the retrospective design and the small sample size. CONCLUSIONS Platinum-based NAC for advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed. PATIENT SUMMARY Platinum-based neoadjuvant chemotherapy for locally advanced upper tract urothelial carcinoma was safe and potentially improves oncological outcomes. A carboplatin-based regimen may be used as an alternative in patients with impaired renal function.

Detecting asymptomatic recurrence after radical cystectomy contributes to better prognosis in patients with muscle-invasive bladder cancer

AbstractThe prognostic benefit of oncological follow-up to detect asymptomatic recurrence after radical cystectomy (RC) remains unclear. We aimed to assess whether routine follow-up to detect asymptomatic recurrence after RC improves patient survival. We retrospectively analyzed 581 RC cases for muscle-invasive bladder cancer at four hospitals between May 1996 and February 2017. All patients had regular follow-up examinations with urine cytology, blood biochemical tests, and computed tomography after RC. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of recurrence (asymptomatic group vs. symptomatic group) was estimated using the Kaplan–Meier method with the log-rank test. Cox proportional hazards regression analysis via inverse probability of treatment weighting (IPTW) was used to evaluate the impact of the mode of diagnosing recurrence on survival. Of the 581 patients, 175 experienced relapse. Among those, 12 without adequate data were excluded. Of the remaining 163 patients, 76 (47%) were asymptomatic and 87 (53%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes (47%) and pain (53%), respectively. Time of overall survival after RC and from recurrence to death was significantly longer in the asymptomatic group than in the symptomatic group. A multivariate Cox regression analysis using IPTW showed that in the patients with symptomatic recurrence was an independent risk factor for overall survival after RC and survival from recurrence to death. Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RC.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer

Objective To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. Methods A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram Results Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). Conclusions Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.OBJECTIVE To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. METHODS A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. RESULTS Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). CONCLUSIONS Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Trends in neoadjuvant chemotherapy use and oncological outcomes for muscle-invasive bladder cancer in Japan: a multicenter study

Objective Despite benefits of neoadjuvant chemotherapy (NAC), the adoption of guideline recommendations for NAC use in patients with muscle-invasive bladder cancer (MIBC) has been slow. We aimed to evaluate temporal trends in NAC use and oncological outcomes in a representative cohort of patients with MIBC. Methods We included 532 patients from 4 hospitals who underwent radical cystectomy (RC) for ≥ cT2 MIBC in 1996–2017. We retrospectively evaluated temporal changes in NAC use and progression-free and overall survival. Candidates for NAC were administered with either cisplatin- or carboplatin-based regimens. The impact of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results Of 532 patients, 336 underwent NAC followed by RC (NAC group) and 196 underwent RC alone (Ctrl group). NAC use significantly increased from 10% (1996–2004) to 83% (2005–2016). The number of patients administered with cisplatin- and carboplatin-based regimens was 43 and 280, respectively. Oncological outcomes in the NAC group were significantly improved compared to those in the Ctrl group. Multivariable analysis with IPTW models revealed that NAC significantly improved oncological outcomes in patients with MIBC. A nomogram for 5-year overall survival predicted 16% improvement in patients undergoing NAC. Conclusions NAC use for MIBC increased after 2005. Platinum-based NAC for MIBC potentially improves oncological outcomes.

Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy.

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

Objective To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. Methods A total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed. Results Of the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively). Conclusions Upper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer

Background The recurrence risk stratification and the cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. Results Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival between normal- and high-risk patients, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. Materials and Methods We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. Conclusions Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.

Efficacy and Safety of Silodosin and Dutasteride Combination Therapy in Acute Urinary Retention due to Benign Prostatic Hyperplasia: A Single-Arm Prospective Study

This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Eighty consecutive patients with a first episode of AUR were enrolled in this study. All patients received silodosin 8 mg and dutasteride 0.5 mg daily. Trial without catheter (TWOC) was attempted every 2 weeks until 12 weeks after the initiation of medication. The primary endpoint was the rate of catheter-free status at 12 weeks. Voided volume (VV), postvoid residual urine (PVR), uroflowmetry, International Prostatic Symptoms Score (IPSS), and quality of life due to urinary symptoms (IPSS-QOL) were also measured. All patients were followed up for more than 12 weeks and were included in this analysis. The success rate of TWOC at 12 weeks was 88.8%. VV and maximum urinary flow rate were significantly higher at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). IPSS and IPSS-QOL were significantly lower at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). In conclusion, a combination of dutasteride and silodosin therapy may be effective and safe for patients with AUR due to BPH.

Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma

Objectives To develop a surveillance protocol with improved cost-effectiveness after radical nephroureterectomy (RNU), as the cost-effectiveness of oncological surveillance after RNU remains unclear. Results Of 426 patients, 109 (26%) and 113 (27%) experienced visceral and intravesical recurrences, respectively. The pathology-based protocol found significant differences in recurrence-free survival in the visceral recurrence but not in the intravesical recurrence. The medical costs per visceral recurrence detected were high, especially in normal-risk (≤ pT2N0, LVI-, SM-) patients. We developed a risk score associated with visceral recurrence using Cox regression analysis. The risk score-based protocol was significantly more cost-effective than the pathology-based protocol. Estimated cost differences reached