Efficacy of Intravesical Instillation Therapy with Low-Dose Tokyo-172 Bacillus Calmette-Guérin to Prevent Recurrence of Non-Muscle-Invasive Bladder Cancer and Treat Carcinoma in situ: A Multi-Institutional Retrospective Study.

INTRODUCTION: There are various doses, durations, and strains of bacillus Calmette-Guérin (BCG) intravesical instillation therapy, but optimal treatment has not yet been established. We retrospectively investigated the efficacy and safety of low-dose BCG therapy for non-muscle-invasive bladder cancer (NMIBC) and carcinoma in situ (CIS) in a multicenter study. METHODS: From 1991 to 2019, 323 patients who received BCG therapy to prevent recurrence of NMIBC were analyzed as group A. Similarly, 147 patients who received BCG therapy for the treatment of CIS were analyzed as group B. Patients received low- or full-dose Tokyo-172 strain or full-dose Connaught strain, and the three strains were compared. Survival curves were estimated by the Kaplan-Meier method, and independent risk factors for intravesical recurrence were examined by multivariate logistic regression. RESULTS: Recurrence-free survival (RFS) in group A was significantly better for the Connaught strain than the low-dose Tokyo-172 strain (p = 0.026), but not between the low- and full-dose Tokyo-172 strains (p = 0.443). RFS of group B, cancer-specific survival, and progression-free survival in both groups did not show statistically significant differences. Logistic analysis of group A showed that for intravesical recurrence, only pT1 was a significant risk factor, and there were no differences between the BCG strain and dose and no significant factors in group B. There were also no differences in the completion rate in both groups, but adverse events such as urinary frequency and feeling of residual urine were significantly lower with the low-dose Tokyo-172 strain. CONCLUSION: There was no difference in efficacy between the low- and full-dose Tokyo-172 strains, but to minimize adverse events, the low-dose Tokyo-172 strain may be worth considering.

Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.

BACKGROUND: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. PATIENTS AND METHODS: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. RESULTS: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. CONCLUSION: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

A multi-institutional retrospective study of open versus laparoscopic nephroureterectomy focused on the intravesical recurrence.

AIM: Intravesical recurrence (IVR) after nephroureterectomy for upper tract urothelial carcinoma (UTUC) is relatively frequent, occurring in about 30-50% of patients. The aim of this study was to investigate the differences of the prognosis and IVR between open and laparoscopic surgery and to elucidate the risk factor of IVR. PATIENTS AND METHODS: We retrospectively analyzed data from 403 patients with UTUC treated with laparoscopic or open nephroureterectomy at six affiliated hospitals between 1990 and 2015. The clinicopathological factors of each group were examined using Kaplan-Meier plots, and univariate and multivariate analyses. RESULTS: There was no difference in recurrence and cancer-specific mortality between open and laparoscopic surgery in univariate and multivariate analyses. There was no significant difference in IVR rate between the laparoscopic and open groups (p = .22). Among the patients with IVR, 84% of patients relapsed within 2 years. Univariate analysis of IVR showed a significant increase in patients with low-grade (p = .03, HR = 1.64) or low-stage urothelial carcinoma (pT1 or lower, p = .006, HR = 1.77) with no lymph node involvement (p = .002, HR = 10.3) or lymphovascular invasion (p = .009, HR = 1.79). Surgical modality was not an independent factor. In multivariate analysis, there was no independent predictive factor for IVR. CONCLUSIONS: There was no difference in recurrence, cancer-specific mortality, and IVR between open and laparoscopic surgery. On the other hand, our results suggested that the low malignant potential tumor may be a risk factor for IVR. This finding provides insight into IVR, which may help with the development of personalized prevention and treatment strategies.

Noninferior oncological outcomes in adults aged 80 years or older compared with younger patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma.

AIM: Radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), but the usefulness of this surgery for older patients is rarely discussed. The prognosis following RNU for patients ≥80 years old remains controversial. We retrospectively investigated the prognosis of UTUC in patients ≥80 years old who underwent RNU. METHODS: Between January 1990 and December 2015, 451 patients with UTUC underwent RNU at six hospitals affiliated with Kitasato University (Kanagawa, Japan), eight patients who underwent neoadjuvant chemotherapy and two patients with metastases before surgery were excluded. Patients were divided into three groups according to their age at the time of RNU: ≤64 years (n = 135), 65-79 years (n = 254), and ≥80 years (n = 52). Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) curves were estimated using Kaplan-Meier analysis for all patients and each pT stage. Independent prognostic factors for survival were examined via multivariate analysis. RESULTS: RFS and CSS did not significantly differ between the three groups, but OS was significantly poorer in patients ≥80 years old. Stratification by pT stage (≤pT1, ≥pT2, and ≥pT3) yielded the same results. In the multivariate analysis for OS, an age of ≥80 years was a significant independent risk factor (hazard ratio: 3.01, p = .01), but RFS and CSS did not significantly differ. CONCLUSION: Oncological outcomes showed the same anticancer effects in patients ≥80 years old who underwent RNU for UTUC compared with those of younger patients. Our study suggests that surgical treatment is a beneficial option for older patients who can tolerate radical surgery.

Real-world treatment patterns and oncological outcomes in early relapse and refractory disease after bacillus Calmette-Guérin failure in non-muscle-invasive bladder cancer.

OBJECTIVE: To assess real-world oncological outcomes between the radical cystectomy (RC) group and non-RC group for early relapse and refractory disease. METHODS: We retrospectively analyzed 953 patients with recurrent non-muscle-invasive bladder cancer (NMIBC) who received bacillus Calmette-Guérin (BCG) at 31 affiliated hospitals from 2000 to 2019. Patients with missing data on the timing of failure were excluded and 871 patients remained eligible, of whom 447, 357, and 67 were classified as early relapse/refractory disease, intermediate/late relapse disease, and intolerant disease, respectively. For early relapse/refractory disease, patients were divided into two salvage treatment groups: RC and non-RC. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios with matched score analyses to compare oncological outcomes between the two groups. RESULTS: Significantly worse progression-free survival and cancer-specific survival (CSS) were confirmed in the early relapse/refractory disease group compared to the intermediate/late relapse group. Of the 88 salvage patients in the RC group with early relapse/refractory disease, ≤pT1 was observed in 47, pT2 in 11, and ≥pT3 in 28 (two patients with unknown pT category). In early relapse/refractory disease, the RC group showed significantly high-risk tumor compared to the non-RC group. However, no significant difference was observed in CSS after matched score analyses (p = 0.45) between the RC and non-RC groups. CONCLUSIONS: This study found that the RC group showed no significant superiority compared to the non-RC group in CSS for early relapse/refractory disease in terms of first salvage therapy.

Impact of salvage cytotoxic chemotherapy on prognosis in patients with recurrence after radical cystectomy: a multi-institutional retrospective study.

BACKGROUND: In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. METHODS: In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient's performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). RESULTS: Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR 1.92; 95% CI 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1-2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. CONCLUSIONS: The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

Intravesical Bacillus Calmette-Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies.

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette-Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000-2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.

PD-L1 expression in tumor-infiltrating lymphocytes (TILs) as an independent predictor of prognosis in patients with pN0 bladder cancer undergoing radical cystectomy.

OBJECTIVES: Checkpoint inhibitors have led to a paradigm shift in urothelial carcinoma (UC) treatment. However, the relationship between PD-L1 expression status and oncological outcomes in UC patients remains uncertain. Here, we investigated the prognostic value of PD-L1 expression status in patients with UC of the bladder (UCB) who underwent radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively analyzed pathological specimens from 97 UCB patients treated with RC from 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining using SP263 was performed to evaluate PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). Kaplan-Meier plots and proportional Cox hazard ratios were examined to assess the relationship between PD-L1 expression and clinicopathological parameters and survival outcomes. RESULTS: Of the 97 specimens, 19.5% contained PD-L1-positive TCs, and 35.0% contained PD-L1-positive TILs. Regarding clinicopathological factors, PD-L1-positive TCs and TILs were significantly associated with high-grade tumors (TCs, P = 0.01; TILs, P = 0.003). Kaplan-Meier analyses showed that PD-L1-positive TCs were not correlated with survival rates. However, PD-L1-positive TILs were significantly associated with better recurrence-free survival (RFS; P = 0.03) and better cancer-specific survival (CSS; P = 0.02). Univariate analysis, but not multivariate analysis, CSS indicated that PD-L1-positive TILs were significant predictors of patient prognoses. Multivariate analysis showed that PD-L1-positive TILs independently predicted CSS in patients without lymph node metastasis (pN0). CONCLUSION: Positive PD-L1 expression is associated with high-grade tumors. PD-L1-positive TILs are independent predictors of favorable survival outcomes in surgically resected UCB patients at stage pN0.

Oncologic Outcomes of Salvage Chemotherapy in Patients with Recurrent or Metastatic Lesions after Radical Nephroureterectomy: A Multi-Institutional Retrospective Study.

BACKGROUND: Radical nephroureterectomy (RNU) is the standard treatment for patients with upper tract urothelial carcinoma (UTUC). However, approximately 25% of patients experience recurrence or metastasis after RNU. This study evaluated the clinical outcome and efficacy of salvage chemotherapy (SC) after recurrence or metastasis. PATIENTS AND METHODS: Of the 441 nonmetastatic UTUC patients who underwent RNU, 147 patients with recurrent or metastatic lesions were analyzed; patients with bladder cancer recurrence were excluded. Time from disease recurrence or metastasis to cancer-specific survival (CSS) was estimated by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. RESULTS: The median time from RNU to disease recurrence or metastasis was 13.2 months. In the recurrent or metastatic sites, 31 cases (21%) were liver. In multivariate analyses, pT stage (≥pT3), time to recurrence (<12 months), and liver metastasis were independently predictive factors. In the risk stratification model for CSS after recurrence, patients were categorized into 2 groups based on pT stage, time to recurrence, and liver metastasis. The low-risk group (0-1 risk factors) included 87 patients, and the high-risk group (2-3 risk factors) included 60 patients. In the high-risk group, 27 patients received SC. The probability of CSS after recurrence or metastasis was higher in patients in the SC group compared to the non-SC group (9.5 vs. 3.7 months; p < 0.001). CONCLUSION: Two or more risk factors defined the high-risk group for patients with recurrence or metastasis after RNU. SC was associated with improved survival in patients with high-risk UTUC.

Prognostic impact of preoperative renal function in patients treated with radical cystectomy: a multi-institutional retrospective study.

BACKGROUND: Little data on the preoperative prognostic factors in radical cystectomy (RC) patients have made it difficult to choose the appropriate type of urothelial diversion (UD). This study aimed to investigate the prognostic role of UD, with a subgroup analysis of that of preoperative renal function. METHODS: From 1990 to 2015, 279 patients underwent RC for bladder cancer at six hospitals affiliated with Kitasato University in Japan. All patients were divided into three groups: cutaneous ureterostomy (CU; n = 54), ileal conduit (IC; n = 139), and orthotopic neobladder (NB; n = 86). Patients were also stratified into three groups based on preoperative estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): normal eGFR (> 60 mL/min/1.73 m2; n = 149), moderately reduced eGFR (45-60 mL/min/1.73 m2; n = 66), and severely reduced eGFR (< 45 mL/min/1.73 m2; n = 37). Statistical analyses were performed to investigate prognostic values of UD and preoperative eGFR. RESULTS: Kaplan-Meier analyses showed that progression-free survival (PFS) and cancer-specific survival (CSS) did not differ between the three types of UD groups. With regard to renal function, the preoperative severely reduced group had significantly worse PFS and CSS than the other groups. The multivariate analysis showed that severely reduced preoperative eGFR was an independent risk factor of worse PFS and worse CSS. CONCLUSION: The present study demonstrated that preoperative severe renal function was shown as an independent risk factor of both PFS and CSS.

Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study.

BACKGROUND: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. METHODS: We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. RESULTS: Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum ß-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL. CONCLUSION: Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Electronic nose to distinguish bladder cancer by urinary odour feature: A pilot study.

BACKGROUND: No study has yet investigated the use of electronic nose (eNose) technology to reveal pattern recognition of urological diseases, including bladder cancer. OBJECTIVE: We sought to determine the diagnostic performance of the eNose in recognizing urinary odour in patients with bladder cancer. METHODS: The eNose is a commercially available model equipped with two sensors. The angle of the two sensors (θ) depends on the kinds of chemical substances, thus defining θ as the feature of odour. Quantity of odour is the number of θ detected during a measurement. Urine samples were from 36 untreated patients with bladder cancer, 29 with urolithiasis, 10 with urinary tract infection (UTI), and 27 healthy volunteers. RESULTS: Based on ROC analysis of the quantity in patients with bladder cancer, an optimal cut-off value for θ of 49, 48, and 55 was applied to compare with samples from the healthy volunteer, urolithiasis and UTI groups, respectively. There were significantly differences between bladder cancer and the other conditions using these specific points (p< 0.0001, respectively). The resulting diagnostic sensitivity was 61.4%, 45.6%, and 60.8%, and specificity was 52.8%, 68.4%, and 90.2%, respectively. The AUC for bladder cancer was 0.565, 0.548, and 0.909, respectively. CONCLUSION: The eNose is a small, portable, rapid, low cost, and noninvasive instrument for distinguishing bladder cancer from other benign conditions.

Quality of life outcomes after low dose-rate brachytherapy for localized prostate cancer: Current status and future perspectives.

The present review summarizes data from studies reporting on health-related quality of life after brachytherapy and competing modalities. There are various therapeutic modalities for localized prostate cancer, including radical surgery, external beam radiotherapy and active surveillance. Advances in surgical and radiation treatment have entered clinical practice in the form of robot-assisted surgery or intensity-modulated radiotherapy. Brachytherapy remains the main treatment option for patients with localized prostate cancer, with 10-year survival data showing favorable outcomes. Because each treatment modality has achieved favorable survival outcomes, focus in determining appropriate treatment has shifted toward health-related quality of life, where each treatment has a different profile and/or adverse symptoms. The development of health-related quality of life assessment tools has allowed the creation of a pool of specific health-related quality of life data across many studies. The present article reviews the impact of brachytherapy and other modalities on quality of life, as well as future directions.

Impact of histologic variants on the oncological outcomes of patients with upper urinary tract cancers treated with radical surgery: a multi-institutional retrospective study.

BACKGROUND: No definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery. PATIENTS AND METHODS: We retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups. RESULTS: HV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS. CONCLUSIONS: HV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.

A Fatal Case of Life-Threatening Interstitial Pneumonitis Induced by Everolimus for Metastatic Renal Cell Carcinoma: A Comment about the Increased Risk of Interstitial Lung Disease in Japanese.

We describe an 81-year-old woman with metastatic renal cell carcinoma who did not recover from life-threatening interstitial pneumonitis induced by everolimus therapy. She received everolimus due to disease progression after sunitinib, but 2 months after starting everolimus treatment, she visited the emergency department after developing a sudden fever and dyspnea. Chest CT revealed diffuse ground-glass opacities, thickening of the interlobular septa, and consolidation throughout both lung fields. The diagnosis was surmised to be everolimus-induced interstitial pneumonitis. Everolimus administration was stopped and 3 courses of steroid pulse therapy were administered, along with intensive care, but the patient died due to rapid respiratory failure.

Histologic variants associated with biological aggressiveness and poor prognosis in patients treated with radical cystectomy.

BACKGROUND: The prognostic value of histologic variants (HV) after radical cystectomy (RC) remains controversial. We evaluated the clinicopathological features and prognosis in patients with pure urothelial carcinoma (UC) and HV following RC. METHODS: From 1990 to 2015, 286 patients with bladder cancer were treated with RC at six Kitasato University-affiliated hospitals. All patients were divided into two groups: pure UC and HV, which contained pure variants and mixed-type UC with variant pattern. A comparison of patient characteristics between the two groups was made to assess the clinicopathological features, and statistical analyses were performed to investigate prognosis in the two groups. RESULTS: Of the 286 patients, 226 (79%) had pure UC, while 60 (21%) had HV. Of all HV, pure variants accounted for 45% (n = 27). The prevalence of lymph node involvement, locally advanced stage (≥ pT3), positive soft tissue surgical margin and lymphovascular invasion were significantly higher in patients with HV than in those with pure UC. Patients with HV showed worse disease-free survival and cancer-specific survival than those with pure UC (P = 0.009 and 0.003, respectively). In multivariate analysis, HV and lymph node involvement were independent predictors of worse disease-free survival (P = 0.017 and 0.001, respectively). HV, locally advanced stage, lymph node involvement, and positive soft tissue surgical margin were also confirmed as independent predictors of worse cancer-specific survival (P = 0.011, 0.012, 0.003 and 0.010, respectively.). CONCLUSIONS: HV was associated with greater biological aggressiveness and worse prognosis than pure UC.

Investigation of estimated glomerular filtration rate and its perioperative change in patients with upper urinary tract urothelial carcinoma: A multi-institutional retrospective study.

AIM: To investigate the association of perioperative estimated glomerular filtration rate (eGFR) with prognosis in patients with upper urinary tract urothoelial caicinoma (UTUC). METHODS: A total of 433 patients underwent radical nephroureterectomy with excision of the bladder cuff (RNU) at six hospitals affiliated with Kitasato University in Japan. Patients were divided into three groups each in terms of preoperative eGFR: normal eGFR (>60 mL/min/1.73 m2 ; n = 172), moderately reduced eGFR (45-60 mL/min/1.73 m2 ; n = 147) and severely reduced eGFR (<45 mL/min/1.73 m2 ; n = 114), and with regard to changes between pre- and postoperative eGFR: normal change (increased or <10% decreased; n = 132), moderate change (10%-30% decreased; n = 172) and severe change (>30% decreased; n = 129). Statistical analyses were performed to investigate the association between perioperative eGFR and prognosis. RESULTS: Patients in the preoperative normal and moderately reduced eGFR group had significantly better progression-free survival (PFS) and cancer-specific survival (CSS) than those in the severely reduced eGFR group (both; P < 0.001). With regard to changes in postoperative eGFR, PFS and CSS were significantly better in patients in the severe and moderate change group than in those in the normal change group (both; P < 0.001). When adjusted for the effects of clinicopathological features, pathologic factors were associated with both PFS and CSS, but perioperative eGFR were not independent prognostic factors. CONCLUSIONS: Patients with preoperative normal and moderately reduced eGFR and those with severe and moderate change in postoperative eGFR appeared to have a significantly better prognosis.

Impact of body mass index on the oncological outcomes of patients with upper and lower urinary tract cancers treated with radical surgery: A multi-institutional retrospective study.

AIM: To evaluate the impact of body mass index (BMI) on the oncological outcomes of urothelial carcinoma (UC) patients. PATIENTS AND METHODS: We retrospectively analyzed data from 818 patients with upper tract urothelial cancer (UTUC) and bladder cancer (BC) who were treated with radical nephroureterectomy (RNU) or radical cystectomy (RC) between 1990 and 2015 at six different institutions in Japan. Patients with distant metastasis at diagnosis and those who received neoadjuvant therapies were excluded, leaving 727 eligible patients (UTUC: n = 441; BC: n = 286). Patients were classified into four groups according to World Health Organization BMI criteria: underweight (BMI <18.5  kg/m2 ), normal weight (BMI 18.5-25 kg/m2 ), overweight (BMI 25.1-30 kg/m2 ), and obese (BMI >30 kg/m2 ). RESULTS: Overweight UTUC and BC patients achieved significantly better cancer-specific survival (CSS) than the other three groups. However, obese UTUC and BC patients had significantly worse CSS than the other three groups (UTUC: P = 0.031; BC: P = 0.0019). Multivariate analysis of BC patients demonstrated that obesity was an independent predictor of unfavorable CSS (hazard ratio [HR] = 7.47; P = 0.002) and that being underweight was an independent predictor of favorable CSS (HR = 0.37; P = 0.029). However, BMI was not a prognostic factor for CSS in UTUC patients according to multivariate analysis. CONCLUSIONS: Obesity was an independent predictor of BC patients requiring RC. Conversely, being underweight was associated with a favorable prognosis for BC patients. However, BMI was not an independent prognostic factor in patients with upper urinary tract cancer.

Selected High-Risk Patients With Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy for Adjuvant Chemotherapy: A Multi-Institutional Retrospective Study.

BACKGROUND: No definitive evidence exists regarding use of adjuvant chemotherapy (AC) for high-risk cases after radical nephroureterectomy (RNU), and the benefit of AC remains controversial. The aims of this study were to evaluate the efficacy of AC in patients with upper tract urothelial carcinoma (UTUC) and to determine those who qualified for AC. PATIENTS AND METHODS: From 1990 to 2015, 449 patients with nonmetastatic UTUC underwent RNU at 6 Kitasato University-affiliated hospitals. Eight patients who received neoadjuvant chemotherapy were excluded from this study. One hundred patients (23%) received platinum-based AC for a median of 3 courses. Disease-free survival and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. RESULTS: The median age was 69 years, and the median follow-up period was 35.7 months. In multivariate analyses, factors independently predictive of poorer survival included pT stage (≥pT3), lymph node status (pN+), tumor grade (Grade 3), lymphovascular invasion, and soft tissue surgical margin. For the risk stratification model, patients were categorized into 3 groups on the basis of these 5 risk factors. In the high-risk group (at least 3 risk factors, 83 patients), 41 patients (49%) were treated with AC, and the 5-year CSS rate was higher in the AC group compared with the non-AC group (P = .02). CONCLUSION: Having more than 3 risk factors defined the high-risk group among UTUC patients after RNU. AC was associated with improved CSS in patients with high-risk UTUC.

Multidisciplinary treatment including systemic chemotherapy for a malignant phyllodes tumour of the prostate.

A 22-year-old man was referred to our hospital with macroscopic hematuria and consistent anal pain. Magnetic resonance imaging revealed an enlarged prostate tumour invading the bladder and rectum. A biopsy revealed an unclassified spindle cell sarcoma. Subsequently, radical cystoprostatectomy and resection of the rectum were performed. A histopathological examination revealed a prostatic malignant phyllodes tumour with a negative surgical margin. However, a local recurrence was identified 2 months after surgery. Induction therapy included 4 cycles of systemic chemotherapy comprising etoposide with ifosfamide and cisplatin. Although a partial response was observed at the local site, lung metastasis developed. Second-line chemotherapy with ifosfamide and doxorubicin with radiotherapy to the pelvis was administered and led to complete regression; however, its efficacy was transient. Although additional chemotherapy was administered, the patient eventually died due to the rapidly growing, recurrent tumour.