Evaluation of Women With a Positive Urine Cytology and no Demonstrable Disease in the Urinary Tract.

Urinary cytology is indispensable both for the evaluation of gross hematuria and surveillance of patients with urothelial neoplasms. A positive urine cytology usually indicates the presence of urothelial carcinoma somewhere in the urinary tract. However, in women, it may also signal urothelial carcinoma involvement of the lower gynecologic tract or be the presenting sign for a primary cancer of the lower gynecologic tract or rectum. Guidelines for the evaluation of women with a positive cytology and normal urinary tract are lacking. We present a review of the current literature with case scenarios to bring clinicians attention to this diagnostic dilemma.

Long-term Outcomes of Local and Metastatic Small Cell Carcinoma of the Urinary Bladder and Genomic Analysis of Patients Treated With Neoadjuvant Chemotherapy.

INTRODUCTION: Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. RESULTS: One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (

Feasibility of a geriatric comanagement (GERICO) pilot program for patients 75 and older undergoing radical cystectomy.

BACKGROUND: Retrospective studies have shown the beneficial impact of geriatric comanagement (GERICO) on perioperative outcomes of older adults with cancer. We prospectively assessed the feasibility of perioperative GERICO for older adults with bladder cancer undergoing radical cystectomy. METHODS: We conducted a pilot study wherein all patients 75 years and older undergoing radical cystectomy between October 2019 and November 2020 were referred to the Geriatric Service preoperatively. Feasibility was defined according to the percentage of patients who received preoperative evaluation by the Geriatrics Service, who were followed for more than 80% of their inpatient days and who had their surgery rescheduled for logistical reasons. Urology advanced practice provider (APP) satisfaction with the program was measured via an 11-item survey. RESULTS: Sixty-six eligible patients underwent radical cystectomy in the stated time frame; 59 (89%; 95% confidence interval [CI], 79-97%) were referred to the Geriatric Service for evaluation. The median age of patients who had geriatric comanagement was 79 years; 40 (68%) were male. Forty-one patients (69%) were visited on at least 80% of the days in which they were not in the intensive care unit. No surgeries were rescheduled for logistical reasons. Nine of the 12 urology APPs (75%) responded to the survey; all nine "somewhat" or "strongly" agreed with statements indicating satisfaction with the program. CONCLUSION: Despite the challenges of the COVID-19 pandemic, we showed that perioperative GERICO is feasible. Fully powered prospective randomized controlled trials should be conducted to assess GERICO's impact on perioperative outcomes of older adults with cancer.

Association of Biochemically Verified Post-Diagnosis Smoking and Nonmuscle-Invasive Bladder Cancer Recurrence Risk.

PURPOSE: Our goal was to determine the association between biochemically verified post-diagnosis smoking exposure and nonmuscle-invasive bladder cancer (NMIBC) recurrence risk. MATERIALS AND METHODS: We conducted a prospective study of 354 NMIBC patients with a smoking history undergoing care between 2015 and 2018. Patients contributed at least 2 biospecimens during followup which were tested for cotinine to determine biochemically verified post-diagnosis smoking exposure (yes/no). Our primary endpoint was time to first recurrence after study start date. We examined whether post-diagnosis smoking exposure was associated with recurrence risk in multivariable Cox proportional hazards models that accounted for demographics, clinicopathological variables, time since diagnosis and pack-years. RESULTS: Patients were predominantly White, male and had a median age of 68 years. Most patients had Ta disease (62%) and tumors of high grade (68%). Intravesical bacillus Calmette-Guérin was given to 63% of the cohort. Patients were followed for a median of 3.6 years since study start. Post-diagnosis smoking exposure was detected in 22% of patients, and 38.7% (137) of patients experienced a recurrence during followup. In multivariable models, only bacillus Calmette-Guérin treatment and prior recurrence rate were significantly associated with recurrence. There was no association between post-diagnosis smoking exposure and recurrence risk (HR: 0.73, 95% CI: 0.45-1.20). CONCLUSIONS: In a cohort of patients with predominantly high risk NMIBC, post-diagnosis smoking exposure was not associated with NMIBC recurrence. However, smoking cessation support remains a critical component of cancer care given that the benefits of quitting extend far beyond NMIBC recurrence.

Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma.

BACKGROUND: Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC. METHODS: Cases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified. RESULTS: We identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively. CONCLUSIONS: PUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.

Examining the Accuracy of Self-Reported Smoking-Related Exposure among Recently Diagnosed Nonmuscle Invasive Bladder Cancer Patients.

PURPOSE: Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients. MATERIALS AND METHODS: This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure. RESULTS: The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure. CONCLUSIONS: Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.

Intraoperative Ureteral Stent Use at Radical Cystectomy is Associated with Higher 30-Day Complication Rates.

PURPOSE: Radical cystectomy/urinary diversion is a high risk procedure. Intraoperative stents are commonly utilized to decrease ureteroenteric anastomosis related complications. Institutionally some surgeons routinely use intraoperative stents while others do not, providing an opportunity to compare complication differences. MATERIALS AND METHODS: We queried a prospective database of 283 patients enrolled in a randomized controlled trial evaluating 30-day perioperative complications with goal directed fluid therapy following open radical cystectomy/urinary diversion between 2014 and 2018. Ureteroenteric anastomosis specific complications (ureteral obstruction, urinary leak, urinary infections/sepsis and intra-abdominal abscess) were compared between groups (intraoperative stent vs nonintraoperative stent group) using Fisher exact test and quantified using logistic regression. RESULTS: The nonintraoperative stent group (77 of 283 patients, 27%) was older (median 72 vs 69 years) and was more likely to receive neoadjuvant chemotherapy (53% vs 40%), have baseline renal insufficiency (43% vs 30%) and undergo an ileal conduit (92% vs 53%). However, despite higher comorbidity, the nonintraoperative stent group had a significantly lower rate of ureteroenteric anastomosis complications (14% vs 32%, p=0.004). Since continent diversions may be associated with higher complications, the nonintraoperative stent group with ileal conduit was also compared to intraoperative stent cohorts with ileal conduit, and ureteroenteric anastomosis complications remained lower in the nonintraoperative stent group (14% vs 28%, p=0.043). Multivariable logistic regression showed significantly increased odds of urinary complications with intraoperative stent use (OR 3.55, 95% CI 2.93-4.31; p <0.0001). Importantly there was no obstruction and only 1 leak (1.3%) in the nonintraoperative stent group. CONCLUSIONS: Contrary to conventional belief, we found intraoperative stent use in radical cystectomy/urinary diversion was associated with significantly higher infectious complications and urgent care visits, and significantly increased the odds of 30-day ureteroenteric anastomosis associated complications.

A Phase II study of salvage high-dose-rate brachytherapy for the treatment of locally recurrent prostate cancer after definitive external beam radiotherapy.

PURPOSE: We report the toxicity and biochemical tumor control outcome of a prospective Phase II study using high-dose-rate brachytherapy (HDR) alone as a salvage therapy for recurrent disease after external beam radiotherapy (EBRT). METHODS: Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192. Median pretreatment EBRT dose was 8100 cGy (6840-8640 cGy) and the median time from completion of EBRT to salvage HDR was 73 months. The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion. Median followup after salvage HDR was 36 months (6-67 months). RESULTS: The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5% and 81.5%, respectively. Cause-specific survival was 90.3%. Late genitourinary Grade 1and 2 toxicities were found in 38% and 48%, respectively, and one patient developed Grade 3 urinary incontinence. Late Grade 1 and 2 gastrointestinal toxicity was noted in 17% and 8% of patients, respectively. Three patients (7%) developed Grade 2 late urinary toxicity (urethral stricture), which were corrected with urethral dilatation, and one patient developed Grade 3 urinary incontinence. No Grade 4 toxicities were observed. CONCLUSIONS: Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon. Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT.

Partial Cystectomy after Neoadjuvant Chemotherapy: Memorial Sloan Kettering Cancer Center Contemporary Experience.

Objective. To report our contemporary experience with partial cystectomy after neoadjuvant chemotherapy. Patients and Methods. Retrospective review of patients who underwent neoadjuvant chemotherapy and partial cystectomy for urothelial cell carcinoma of the bladder at Memorial Sloan Kettering Cancer Center from 1995 to 2013. Log-rank test and Cox regression models were used to analyze variables possibly associated with recurrence-free, advanced recurrence-free (free from recurrence beyond salvage with intravesical therapy or radical cystectomy), and overall survival. Results. All 36 patients had a solitary tumor <5 cm in size. Twenty-one patients (58%) achieved cT0 following neoadjuvant chemotherapy with 7 (33%) having residual disease at PC. At last follow-up, 19 (53%) patients had recurrence, 15 (42%) had advanced recurrence, 10 (28%) died of disease, and 22 (61%) maintained an intact bladder. Median follow-up of those who were with no evidence of disease was 17 months. On univariable analysis, after neoadjuvant chemotherapy positive nodes on imaging and positive surgical margin at partial cystectomy were both associated with worse recurrence-free, advanced recurrence-free, and overall survival. Five-year recurrence-free, advanced recurrence-free, and overall survival were 28%, 51%, and 63%, respectively. Conclusion. Partial cystectomy following neoadjuvant chemotherapy provides acceptable oncologic outcomes in highly selected patients with muscle-invasive bladder cancer.

Upper tract imaging surveillance is not effective in diagnosing upper tract recurrence in patients followed for nonmuscle invasive bladder cancer.

PURPOSE: We evaluated the usefulness of routine upper tract imaging in patients followed for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: A retrospective review of patients treated for nonmuscle invasive bladder cancer between 2000 and 2006 was conducted. Kaplan-Meier curves were calculated to determine upper tract urothelial carcinoma-free probability for stage Ta and T1 disease. Bladder cancer stage was included as a time dependent covariate. Descriptive statistics were used to report rates of imaging studies used and the efficacy in diagnosing upper tract urothelial carcinoma. RESULTS: Of 935 patients treated and followed for nonmuscle invasive bladder cancer 51 were diagnosed with upper tract urothelial carcinoma. Median followup was 5.5 years. The 5-year upper tract urothelial carcinoma-free probability among patients with Ta and T1 disease was 98% and 93%, respectively. The 10-year upper tract urothelial carcinoma-free probability among patients with Ta and T1 disease was 94% and 88%, respectively. Only 15 (29%) patients were diagnosed on routine imaging while the others were diagnosed after symptoms developed. Overall 3,074 routine imaging scans were conducted for an overall efficacy of 0.49%. CONCLUSIONS: Upper tract recurrence is a lifelong risk in patients with bladder cancer, but most cases will be missed on routine upper tract imaging. The majority of upper tract urothelial carcinoma can be diagnosed using a combination of thorough history taking, physical examination, urine cytology and sonography, indicating that routine surveillance imaging may not be the most efficient way to detect upper tract recurrence.

Follow-up for Clinically Localized Renal Neoplasms: AUA Guideline.

PURPOSE: The purpose of this guideline is to provide a clinical framework for follow-up of clinically localized renal neoplasms undergoing active surveillance, or following definitive therapy. MATERIALS AND METHODS: A systematic literature review identified published articles in the English literature between January 1999 and 2011 relevant to key questions specified by the Panel related to kidney neoplasms and their follow-up (imaging, renal function, markers, biopsy, prognosis). Study designs consisting of clinical trials (randomized or not), observational studies (cohort, case-control, case series) and systematic reviews were included. RESULTS: Guideline statements provided guidance for ongoing evaluation of renal function, usefulness of renal biopsy, timing/type of radiographic imaging and formulation of future research initiatives. A lack of studies precluded risk stratification beyond tumor staging; therefore, for the purposes of postoperative surveillance guidelines, patients with localized renal cancers were grouped into strata of low- and moderate- to high-risk for disease recurrence based on pathological tumor stage. CONCLUSIONS: Evaluation for patients on active surveillance and following definitive therapy for renal neoplasms should include physical examination, renal function, serum studies and imaging and should be tailored according to recurrence risk, comorbidities and monitoring for treatment sequelae. Expert opinion determined a judicious course of monitoring/surveillance that may change in intensity as surgical/ablative therapies evolve, renal biopsy accuracy improves and more long-term follow-up data are collected. The beneficial impact of careful follow-up will also need critical evaluation as further study is completed.

Intravesical gemcitabine for high risk, nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure.

PURPOSE: We report our experience with intravesical gemcitabine for bladder cancer after failed bacillus Calmette-Guérin treatment. MATERIALS AND METHODS: We retrospectively reviewed the records of patients at our cancer center treated with intravesical gemcitabine after bacillus Calmette-Guérin failure. We estimated progression-free, recurrence-free and cancer specific survival using the cumulative incidence function, considering death from another cause as a competing risk. Comparisons were made using the Gray test. Overall survival was estimated using the Kaplan-Meier method and differences were compared with the log rank test. RESULTS: Of 69 patients treated with intravesical gemcitabine 37 had bacillus Calmette-Guérin refractory disease. Median followup in progression-free patients was 3.3 years. Progression-free and cancer specific survival were similar in patients with refractory disease and those with other types of bacillus Calmette-Guérin failure. Overall survival was lower in patients with refractory disease (58% vs 71%) but this was not statistically significant (p=0.096). Of the patients 27 patients experienced a complete response. Progression-free, cancer specific and overall survival did not differ significantly between patients with and without a complete response. Cystectomy was subsequently performed in 20 patients. Those with a complete response had a delayed time to cystectomy and no muscle invasive bladder cancer at cystectomy. There were no serious adverse events and only a minority of patients discontinued treatment due to adverse events. CONCLUSIONS: In our experience intravesical gemcitabine should be considered after bacillus Calmette-Guérin failure in patients with bladder cancer who refuse radical cystectomy or who are not candidates for major surgery.

Assessment of complication and functional outcome reporting in the minimally invasive prostatectomy literature from 2006 to the present.

To query the minimally invasive urological literature from 2006 to the middle of 2010, focusing on complications and functional outcome reporting in laparoscopic radical prostatectomy (LRP) and robot-assisted LRP (RALP), to see if there has been an improvement in the overall reporting of complications. We performed a Medline search using the Medical Subject Heading terms 'prostatectomy', 'laparoscopy', 'robotics', and 'minimally invasive'. We then applied the Martin criteria for complications reporting to the selected articles. We identified 51 studies for a total of 32,680 patients. When excluding functional outcomes the outpatient complications reporting was 20/51 (39.2%). In all, 35% and 43% of papers did not list any method for recording continence and potency, respectively. A complication grading system was only used in 30 studies (58.8%). Of the 16 papers using a grading scale in 2006-2007, only 31.3% used the Clavien system, compared with 69% from 2008 to the first half of 2010. In all, 27% of papers used some form of risk-factor analysis for complications. Multivariate analysis was used in 43% of papers, 29% looked at body mass index, while one looked at prostate weight, and another age. There has been an overall improvement in complications reporting in the minimally invasive RP literature since 2005. However, most studies still do not fulfil many of the criteria necessary for standardised complication reporting. Functional outcome reporting remains poor and unstandardised. Given our current reliance on observational studies, increased efforts should be made to standardise all complication outcomes reporting.

Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy. OBJECTIVE: We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer. INTERVENTION: Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr. MEASUREMENTS: End points were 5-yr tumor- and progression-free survival rates. RESULTS AND LIMITATIONS: Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments. CONCLUSIONS: Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.

Reduced bladder tumour recurrence rate associated with narrow-band imaging surveillance cystoscopy.

OBJECTIVE: To evaluate frequency of recurrences among patients with papillary bladder tumours followed sequentially with conventional white-light (WLI) cystoscopy and narrow-band imaging (NBI) cystoscopy. PATIENTS AND METHODS: A cohort of 126 patients with recurrent low-grade papillary bladder tumours were followed every 6 months for 3 years by conventional WLI cystoscopy, and then over the next 3 consecutive years by NBI cystoscopy. Recurrent tumours detected were treated by outpatient fulguration or transurethral resection. We compared the tumour recurrence rate during follow-up with WLI and NBI cystoscopy, using patients as their own controls. RESULTS: Of the 126 patients, 94% had tumour recurrences during WLI cystoscopy vs 62% during NBI cystoscopy. The mean number of recurrent tumours was 5.2 with WLI cystoscopy vs 2.8 with NBI cystoscopy, and the median recurrence-free survival time was 13 vs 29 months (P= 0.001). CONCLUSION: Compared with follow-up with WLI cystoscopy, NBI cystoscopy was associated with fewer patients having tumour recurrences, fewer numbers of recurrent tumours, and a longer recurrence-free survival time.

Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer.

PURPOSE: Historically patients with recurrent T1 bladder tumors after bacillus Calmette-Guerin have been treated with bladder sparing approaches. Recently a paradigm shift has occurred since patients are increasingly offered radical cystectomy before disease progression to muscle invasion. In this study we explored the effect of this paradigm shift on progression rates and disease specific survival. MATERIALS AND METHODS: The historical cohort consisted of 307 patients from 3 prospective intravesical bacillus Calmette-Guerin protocols from 1980 to 1989. An institutional review board approved review identified 589 patients treated with bacillus Calmette-Guerin in a contemporary cohort from 1992 to 2004. RESULTS: In the historical cohort the 85 patients with documented T1 recurrence were initially treated with repeat transurethral resection and intravesical bacillus Calmette-Guerin. Of these 85 patients 60 had progression to muscle invasive disease. At 5 years after T1 recurrence, the cumulative incidence of progression to T2 disease was 71% (95% CI 61%, 81%) and the cumulative incidence of death from disease was 48% (95% CI 39%, 60%). In the contemporary cohort 129 patients had documented T1 recurrence. In this cohort 65 of the 129 patients with recurrent T1 underwent immediate radical cystectomy. At 5 years after T1 recurrence, the cumulative incidence of progression to muscle invasive disease was 28% (95% CI 20%, 38%) and the cumulative incidence of death from disease was 31% (95% CI 22%, 42%). CONCLUSIONS: Preemptive radical cystectomy performed for recurrent T1 disease following intravesical bacillus Calmette-Guerin therapy may be associated with better disease specific survival.