Toshiaki Kawaguchi

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.

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 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.

Detecting asymptomatic recurrence after radical nephroureterectomy contributes to better prognosis in patients with upper urinary tract urothelial carcinoma

Background The prognostic benefit of regular follow-up to detect asymptomatic recurrence after radical nephroureterectomy (RNU) remains unclear. We aimed to assess whether regular follow-up to detect asymptomatic recurrence after RNU improves patient survival. Materials and Methods We retrospectively analysed 415 patients who underwent RNU for upper tract urothelial carcinoma at four hospitals between January 1995 and February 2017. All patients had regular follow-up examinations after RNU including urine cytology, blood biochemical tests, and computed tomography. We investigated the first site and date of tumor recurrence. Overall survivals of patients who developed recurrence, stratified by mode of recurrence (asymptomatic vs. symptomatic group), were estimated using the Kaplan–Meier method with the log–rank test. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of the mode of recurrence on survival. Results Of the 415 patients, 108 (26%) experienced disease recurrences after RNU. Of these, 62 (57%) were asymptomatic and 46 (43%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes and pain, respectively. Overall survival after RNU and time from recurrence to death in the asymptomatic group were significantly longer than that in the symptomatic group. Multivariate Cox regression analysis showed that symptomatic recurrence was an independent risk factor for overall survival after RNU and survival from recurrence to death. Conclusions Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RNU.

Impact of bacillus Calmette–Guérin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy

The clinical benefits of bacillus Calmette–Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS) remain unclear. We aimed to compare the efficacy and safety of BCG therapy for upper urinary tract CIS with those of radical nephroureterectomy (RNU). Of 490 patients with upper urinary tract carcinoma, we retrospectively reviewed the post-treatment course of 58 patients with upper urinary tract CIS who underwent either RNU (RNU group) or BCG therapy (BCG group). Efficacy and safety were compared between the RNU and BCG groups. Inverse probability treatment-weighted (IPTW)-adjusted multivariate Cox regression analysis was performed to identify the influence of BCG therapy on prognosis. The RNU and BCG groups included 20 and 38 patients, respectively. No significant difference was found in patients’ background, including age, sex, and performance status, between the groups. The reason underlying the selection of BCG therapy was bilateral CIS of the upper urinary tract (50%), solitary kidney (26%), unwillingness to undergo RNU (13%), and ineligibility for surgery (11%). The cytology became negative in 30 (79%) out of 38 patients after a 6-week course of BCG therapy, and 17 (57%) out of 30 patients remained negative. BCG-related adverse events (AEs) were observed in 92% of patients. The most common AE was cystitis (76%), followed by fever (50%). No significant differences were found in the progression-free, cancer-specific, and overall survivals between the RNU and BCG groups. IPTW-adjusted multivariate analysis revealed that BCG therapy did not worsen the prognosis of these patients. The limitations of our study were its retrospective design and small sample size. In conclusion, BCG therapy for upper urinary tract CIS might be a useful alternative for patient ineligible for RNU under careful observation for AEs.

The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma

BACKGROUND The impact of preoperative renal impairment severity on prognosis in urothelial carcinoma remains unelucidated. OBJECTIVE To evaluate the impact of severe preoperative renal insufficiency on oncological outcomes in patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy. DESIGN, SETTING, AND PARTICIPANTS A total of 1066 patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy at six medical centres from February 1995 to November 2017 were retrospectively examined. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Oncological outcomes, stratified using preoperative estimated glomerular filtration rate (eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2), were investigated. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis was performed to evaluate the impact of preoperative eGFR on prognosis. RESULTS AND LIMITATIONS Of 610 patients with muscle-invasive bladder cancer (MIBC), 80 (13%) had severe renal insufficiency (eGFR<45ml/min/1.73m2). Of 456 patients with upper tract urothelial carcinoma (UTUC), 101 (22%) had severe renal insufficiency. Significant differences were noted in background and prognosis among the patients with preoperative eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2. Findings of IPTW-adjusted Cox regression analysis demonstrated that preoperative eGFR<45ml/min/1.73m2 was significantly associated with poor postsurgical recurrence-free, cancer-specific and overall survival rates in patients with either MIBC or UTUC. CONCLUSIONS Patients with urothelial carcinoma with preoperative eGFR<45ml/min/1.73m2 had a significantly lower survival probability than those without. PATIENT SUMMARY In this report, we found that preoperative severe renal insufficiency (estimated glomerular filtration rate<45ml/min/1.73m2) had higher risk for relapse and lower survival probability. Close attention is necessary when urothelial carcinoma patients have severe renal insufficiency before radical cystectomy or nephroureterectomy.

567 Eviprostat has an identical effect compared to pollen extract (Cernilton) in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study

Background Previously reported results of a prospective, randomized placebo-controlled study showed that the pollen extract (Cernilton) significantly improved total symptoms, pain, and quality of life in patients with inflammatory prostatitis/chronic pelvic pain syndrome (CP/CPPS) without severe side effects. A phytotherapeutic agent, Eviprostat, is reportedly effective in a rat model of nonbacterial prostatitis. The aim of the present study was to compare the efficacy and safety of Eviprostat to that of the pollen extract in the management of CP/CPPS.