Molecular Profiles of Prostate Cancer: To Treat or Not to Treat.

A major dilemma in the selection of treatment for men with prostate cancer is the difficulty in accurately characterizing the risk posed by the cancer. This uncertainty has led physicians to recommend aggressive therapy for most men diagnosed with prostate cancer and has led to concerns about the benefits of screening and the adverse consequences of excessive treatment. Genomic analyses of prostate cancer reveal distinct patterns of alterations in the genomic landscape of the disease that show promise for improved prediction of prognosis and better medical decision making. Several molecular profiles are now commercially available and are being used to inform medical decisions. This article describes the clinical tests available for distinguishing aggressive from nonaggressive prostate cancer, reviews the new genomic tests, and discusses their advantages and limitations and the evidence for their utility in various clinical settings.

Age is Associated with Upgrading at Confirmatory Biopsy among Men with Prostate Cancer Treated with Active Surveillance.

PURPOSE: Active surveillance is increasingly recommended for older men with low risk prostate cancer. Although older men have higher all cause mortality, they also have higher prostate cancer specific mortality. We hypothesized that older age is associated with an increased risk of Gleason score upgrading at confirmatory biopsy when controlling for prostate volume. MATERIALS AND METHODS: We retrospectively reviewed data on 1,130 patients with prostate cancer who were treated with active surveillance from 1991 through 2011. We included 646 patients with clinical Gleason 6 or less, stage T2a or less prostate cancer, a confirmatory biopsy within 2 years of diagnostic biopsy and prostate magnetic resonance imaging before confirmatory biopsy. The primary outcome was Gleason score upgrading to 7 or greater on confirmatory biopsy. We used logistic regression to estimate the effect of age on upgrading, adjusting for magnetic resonance imaging prostate volume and other potential confounders. RESULTS: Median age was 66 years (IQR 61-72) and median magnetic resonance imaging prostate volume was 41 ml (IQR 29-55). At confirmatory biopsy disease was upgraded in 55 of 646 patients (9%) and unchanged in 290 (45%) and biopsy was negative in 297 (46%). Older age was associated with higher odds of upgrading (adjusted OR 1.05, 95% CI 1.01-1.09, p=0.009). Larger prostate volume was associated with lower odds of upgrading (adjusted OR 0.80/10 ml increase, 95% CI 0.7-0.9, p=0.012). CONCLUSIONS: Our findings suggest that older age is associated with an increased risk of misclassification on diagnostic biopsy. Older men who are interested in active surveillance should be counseled about the risks and benefits of confirmatory biopsy.

Can renal hemangiomas be diagnosed preoperatively?

BACKGROUND: Renal hemangiomas are rare benign tumors seldom distinguished from malignant tumors preoperatively. OBJECTIVES: To describe the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal hemangiomas, and to explore possible clinical and radiologic features that can aid in diagnosing renal hemangiomas preoperatively. METHODS: Patients with renal hemangiomas treated at MSKCC were identified in our prospectively collected renal tumor database. Descriptive statistics were used to describe the patient characteristics and the tumor characteristics. All available preoperative imaging studies were reviewed to assess common findings and explore possible characteristics distinguishing benign hemangiomas from malignant renal tumors preoperatively. RESULTS: Of 6341 patients in our database 15 were identified. Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected side was evenly distributed. All but two patients were treated surgically. The mean decrease in estimated glomerular filtration rate (eGFR) after surgery was 36.3%; one patient had an abnormal presurgical eGFR and only two patients had a normal eGFR after surgery. We could not identify radiographic features that would make preoperative diagnosis certain, but we did identify features characteristic of hepatic hemangiomas that were also present in some of the renal hemangiomas. CONCLUSIONS: Most renal hemangiomas cannot be distinguished from other common renal cortical tumors preoperatively. In select cases a renal biopsy can identify this benign lesion and the deleterious effects of extirpative surgery can be avoided.

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.

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.

Role of immediate radical cystectomy in the treatment of patients with residual T1 bladder cancer on restaging transurethral resection.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Bladder cancer patients with lamina propria invasion (T1 disease) and residual T1 disease on restaging transurethral resection of bladder tumour (re-TURBT) are at a very high risk for recurrence and progression. Despite this risk, most patients are treated with a bladder preserving approach and not immediate radical cystectomy (RC). In this study we have shown that a quarter of patients with T1 bladder cancer and residual T1 on re-TURBT who are treated with immediate RC are found to have carcinoma invading bladder muscle at RC and 5% have lymph node metastases. We have also found that >30% of patients treated with deferred RC after initial bladder-preserving therapy harbour carcinoma invading bladder muscle and almost 20% of these patients have lymph node metastases. Thus, immediate RC should be considered in all patients with T1 bladder cancer and residual T1 on re-TURBT. OBJECTIVE: To report the overall survival (OS) and cancer-specific survival (CSS) of patients with residual T1 bladder cancer on restaging transurethral resection of the bladder tumour (re-TURBT). MATERIALS AND METHODS: We performed a retrospective review of 150 evaluable patients treated for T1 bladder cancer with residual T1 disease found on re-TURBT between 1990 and 2007. Patients were treated with immediate radical cystectomy (RC) or a bladder-preserving approach (deferred or no RC). A univariate Cox proportional hazards regression model was used to test the association between treatment approach and survival. RESULTS: Residual T1 bladder cancer was found in 150 evaluable patients, of whom 57 received immediate RC and 93 were treated with a bladder-preserving approach. Fourteen out of 57 patients receiving immediate RC and 8/26 patients receiving deferred RC had carcinoma invading bladder muscle in the RC specimen. Three out of 57 and 5/26 patients had lymph node metastases in the RC specimen. Median follow-up was 3.74 years. Thirty-nine patients died during follow-up, 16 from bladder cancer. There was no significant association between immediate RC and CSS (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.43-3.09, P = 0.8) or OS (HR 0.79, 95% CI 0.4-1.53, P = 0.5). CONCLUSIONS: Because of the low number of events we cannot conclude whether RC offers a survival advantage in patients with residual T1 bladder cancer on re-TURBT. Since a quarter of patients had carcinoma invading bladder muscle, RC should be considered in these patients. A larger, preferably randomized, study with longer follow-up is needed.

Association between COVID-19 Burden, Population Vaccination Status, and Urologic Oncology Surgery Volume: A National Multicenter Cross-Sectional Study.

Initial deleterious effects of the COVID-19 pandemic on urologic oncology surgeries are well described, but the possible influence of vaccination efforts and those of pandemic conditions on surgical volumes is unclear. Our aim was to examine the association between changing vaccination status and COVID-19 burden throughout the pandemic and the volume of urologic oncology surgeries in Israel. This multi-center cross-sectional study included data collected from five tertiary centers between January 2019 and December 2021. All 7327 urologic oncology surgeries were included. Epidemiological data were obtained from the Israeli Ministry of Health database. A rising trend in total urologic oncology surgery volumes was observed with ensuing COVID-19 wave peaks over time (X2 = 13.184, df = 3, p = 0.004). Total monthly surgical volumes correlated with total monthly hospitalizations due to COVID-19 (R = -0.36, p = 0.015), as well as with the monthly average Oxford Stringency Index (R = -0.31, p = 0.035). The cumulative percent of vaccinations and of new COVID-19 cases per month did not correlate with total monthly urologic surgery volumes. Our study demonstrates the gradual acclimation of the Israeli healthcare system to the COVID-19 pandemic. However, hospitalizations due to COVID-19, as well as restriction stringency, correlate with lower volumes of urologic oncological surgeries, regardless of the population's vaccination status.

Uroflowmetry Before and After Meatotomy in Boys with Symptomatic Meatal Stenosis Following Neonatal Circumcision - A Long-term Prospective Study.

OBJECTIVE: To assess uroflowmetry in the long-term follow-up of symptomatic meatal stenosis patients prior to and following meatotomy. Severity of symptoms and treatment success has been defined by patient history, physical examination, and witnessed voiding. Uroflowmetry might add objective parameters for the assessment, however long-term data are lacking. METHODS: A prospective study following 25 symptomatic toilet-trained boys before and after meatotomy was performed with short and long-term follow-up after surgery. Patient history, physical examination, and uroflowmetry variables were recorded. RESULTS: Fifteen patients were fully evaluable. Mean age at operation was 6.4 years (2.5-10.5) with an average follow-up of 43 months. All patients were symptomatic before surgery; complete symptomatic resolution was achieved in all patients at short-term follow-up, and in 12 at long-term follow-up. A stenotic meatus was seen in all patients before surgery, at long-term follow-up 12 of 15 (80%) had an open appearing meatus (P = .0001). Abnormal uroflowmetry pattern was present in 8 of 15 (53%) prior to surgery and 2 of 15 (13%) at long-term follow-up (P = .02). Normal maximal flow rate as defined by ICCS were seen in 5, 11, and 12 patients before, 1 month after and at long-term follow-up (P = .06 and 0.02, respectively). PVR improved significantly at long-term follow-up (P = .0012). CONCLUSION: Symptom evaluation and physical examination should be the hallmark assessing children with meatal stenosis. Clinical assessment one month after surgery suffices and long-term follow-up is unnecessary. Uroflowmetry provides objective assessment as well as surgical success; however, it is unnecessary since it does not change the management.

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial.

BACKGROUND: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer. OBJECTIVE: To assess the performance of BE for NMIBC recurrence. DESIGN, SETTING, AND PARTICIPANTS: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age ≥22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10ml of urine, and able to consent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology. RESULTS AND LIMITATIONS: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively. CONCLUSIONS: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced. PATIENT SUMMARY: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens.

Surgical Treatment of Tumors Involving Kidneys With Fusion Anomalies: A Contemporary Series.

OBJECTIVE: To report a contemporary series of surgically treated patients with tumors involving kidneys with fusion anomalies. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all 10 patients treated at a single tertiary care institution for tumors involving kidneys with fusion anomalies between the years 2000 and 2015. One patient, diagnosed with lymphoma, did not undergo surgical treatment and was therefore excluded. Data regarding patient, tumor, and treatment characteristics were collected and described. RESULTS: The study cohort included 7 male and 2 female patients, at a median age of 52 years. Seven patients underwent open partial nephrectomy. Nephroureterectomy was performed on 2 patients; 1 open and 1 laparoscopic. All patients had localized disease at diagnosis. Tumor histologies were renal cell carcinoma in 5 patients, renal oncocytoma in 1 patient, urothelial carcinoma in 2 patients, and a well-differentiated liposarcoma involving the kidney in 1 patient. Accessory blood vessels were identified in 8 of 9 patients. Median estimated blood loss was 300 mL (interquartile range: 150-1000). Four patients had postoperative complications, including 3 major (Clavien grade ≥ 3) and 3 minor (Clavien grade ≤ 2) complications. During a median follow-up of 19.2 months (interquartile range: 3-34.8), 1 patient with urothelial carcinoma developed a bladder recurrence. None of the patients developed new-onset chronic kidney disease during the early postoperative period. CONCLUSION: Localized renal cortical tumors in kidneys with fusion anomalies may be treated with partial nephrectomy; however, complication rates are relatively high. Preoperative imaging of the blood vessels is necessary, as most patients have an accessory blood supply.

The effect of delaying nephrectomy on oncologic outcomes in patients with renal tumors greater than 4cm.

OBJECTIVES: Delaying nephrectomy<3 months does not adversely affect treatment outcome of renal tumors. Whether surgical waiting time (SWT; time from diagnosis to surgery)>3 months affects treatment outcome for large renal masses has not been well studied. We aimed to evaluate if SWT is associated with treatment outcome of renal masses >4cm and identify patients who are more likely to experience prolonged SWT. MATERIALS AND METHODS: Data from 1,484 patients undergoing radical or partial nephrectomy at a single institution for a nonmetastatic renal mass>4cm between 1995 and 2013 were reviewed. Patients with benign tumors and incomplete preoperative data were excluded. The association between SWT and disease upstaging at the time of surgery and recurrence at 2 and 5 years was assessed using logistic regression. Cancer-specific survival (CSS) and overall survival were assessed with landmark survival analyses and multivariable Cox proportional hazards models. All analyses were adjusted for patient and tumor characteristics. RESULTS: Of the final cohort of 1,278 patients, 267 (21%) had SWT>3 months. Patients with larger, symptomatic tumors had shorter SWT. Median follow-up for survivors was 3.8 years (interquartile range: 1.5-7.4). On multivariable analysis, SWT was not associated with disease upstaging, recurrence, or CSS. Longer SWT was associated with decreased overall survival (hazard ratio = 1.17; 95% CI: 1.08-1.27; P = 0.0002). Sex and tumor size, histology, and presentation were associated with disease upstaging, recurrence, and CSS. The most common cause for surgical delay>3 months was evaluation and treatment of comorbidities. CONCLUSION: Patient and tumor characteristics, rather than SWT, were associated with disease upstaging, recurrence, and CSS, and should guide the decision to delay surgery when treating nonmetastatic renal tumors>4cm.

Partial and Radical Nephrectomy for Unilateral Synchronous Multifocal Renal Cortical Tumors.

OBJECTIVE: To evaluate clinicopathologic characteristics and treatment outcomes of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for unilateral synchronous multifocal renal tumors. METHODS: We retrospectively reviewed medical records for 128 patients with nonmetastatic, unilateral, synchronous, multifocal renal tumors who underwent surgical resection at our institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma were excluded. Differences between patient and tumor characteristics from the 2 nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival, overall survival, and chronic kidney disease upstaging were estimated using Kaplan-Meier methods. The log-rank test was used for group comparisons. RESULTS: The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17 of 95 planned PN (18%) were converted to RN. Tumor diameter and RENAL nephrometry scores were greater in RN patients (P <.0001 and P = .0002, respectively). Pathologic stage T3 was seen in 40% of RN patients and 10% of PN patients (P = .0002). Histologic concordance was apparent in 60 of 123 patients (49%). Median follow-up for patients alive without a recurrence was 4 years. Five-year recurrence-free survival was 98% for PN and 85% for RN. Five-year overall survival was 96% for PN and 86% for RN (P = .5). Five-year freedom from chronic kidney disease upstaging was 74% for PN and 55% for RN (P = .11). CONCLUSION: Partial nephrectomy for the treatment of unilateral, synchronous, multifocal, renal tumors with favorable characteristics was associated with a low recurrence rate. These findings suggest PN is an appropriate management strategy for this group of carefully selected patients.

Cost comparison of open and robotic partial nephrectomy using a short postoperative pathway.

OBJECTIVE: To compare immediate perioperative direct costs of open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN), managed under a common care pathway. METHODS: Retrospective review of detailed institutional cost data for patients treated with OPN and RPN during 2011 was conducted. Cost and clinical data of OPN and RPN were compared for all patients and for patients stratified by length of stay (LOS), American Society of Anesthesiologists (ASA), and RENAL nephrometry scores. RESULTS: The study cohort included 190 OPN and 63 RPN cases. OPN was associated with higher ASA scores (P <.001), shorter operative times (P = .014), and higher estimated blood loss (P <.001). Median (interquartile range) LOS was 2 days (2-3 days) for OPN compared with 1 day (1-2 days) for RPN (P <.001). Median perioperative cost of OPN was lower than that of RPN with a difference of $3091 (P <.001). Although hospitalization costs were higher in OPN, surgical costs were higher in RPN ($854 and $3695 difference in median costs, respectively; P <.001 for both). The total cost of OPN for patients with an above-average LOS remained lower than that of RPN ($2680 difference in median costs; P = .001). RPN costs remained significantly higher when stratifying patients by their ASA and RENAL nephrometry scores. CONCLUSION: Despite the shorter hospital LOS associated with RPN, the immediate perioperative cost of OPN was lower than that of RPN for patients managed under a common care pathway, mainly due to high robotic purchase and maintenance costs. In light of the current health care debate, such financial disincentives may compromise the sustainability of advances in medical technology.

Definitive pathology at radical prostatectomy is commonly favorable in men following initial active surveillance.

BACKGROUND: Limited data are currently available regarding the outcomes of radical prostatectomy (RP) in men with low-risk prostate cancer who were initially managed by active surveillance (AS). OBJECTIVE: To evaluate the pathologic outcomes of patients who underwent RP following initial AS. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the records of 67 patients who underwent RP following initial AS begun between 1993 and 2011. All patients underwent confirmatory biopsy to reassess eligibility for AS. RP was recommended for disease progression suggested by follow-up biopsies or imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Unfavorable disease was defined as having at least one of the following pathologic findings: Gleason score (GS) ≥4+3, extracapsular extension of tumor, seminal vesicle invasion, or lymph node involvement. A descriptive analysis was performed to assess pathologic features. RESULTS AND LIMITATIONS: Median time from confirmatory biopsy to RP was 1.7 yr (range: 0.3-7.8). Reasons for discontinuing AS to undergo RP included evidence of increased tumor volume or grade on follow-up biopsy, patient preference/anxiety, and findings on follow-up imaging in 46 patients (68.7%), 17 patients (25.3%), and 4 patients (6.0%), respectively. Pathologic analyses revealed organ-confined disease in 55 patients (82.1%), and GS was ≥4+3 in 9 (13.4%). Positive nodes were observed in three patients (4.4%) and positive surgical margin in two (3.0%). Overall, 19 patients (28.4%) had unfavorable disease. Of the biopsy criteria for triggering RP, Gleason patterns >3 were the most frequently associated with unfavorable disease (43.3%). One patient (1.5%) experienced biochemical recurrence during postoperative follow-up (median: 3.2 yr). Our study may be limited by its retrospective and single-institution nature. CONCLUSIONS: Most patients who started initially on AS after undergoing confirmatory biopsy showed pathologically organ-confined disease with a low GS at RP. Such findings provide further evidence that, overall, AS is a safe treatment approach.