Practical Use of Self-Adjusted Nitrous Oxide During Transrectal Prostate Biopsy: A Double-Blind Randomized Controlled Trial.

PURPOSE: Transrectal prostate biopsy is a common ambulatory procedure that can result in pain and anxiety for some men. Low-dose, adjustable nitrous oxide is increasingly being used to improve experience of care for patients undergoing painful procedures. This study seeks to evaluate the efficacy and safety of low-dose (<45%) nitrous oxide, which has not been previously established for transrectal prostate biopsies. MATERIALS AND METHODS: A single-institution, prospective, double-blind, randomized, controlled trial was conducted on patients undergoing transrectal prostate biopsies. Patients were randomized to receive either self-adjusted nitrous oxide or oxygen, in addition to routine periprostatic bupivacaine block. Nitrous oxide at levels between 20% and 45% were adjusted to patients' desired effect. Patients completed a visual analog scale for anxiety, State Trait Anxiety Inventory, and a visual analog scale for pain immediately before and after biopsy. The blinded operating urologist evaluated ease of procedure. Periprocedural vitals and complications were assessed. Patients were allowed to drive home independently. RESULTS: A total of 133 patients received either nitrous oxide (66) or oxygen (67). There was no statistically significant difference in the primary anxiety end point of State Trait Anxiety Inventory or the visual analog scale for anxiety scores between the nitrous oxide and oxygen groups. However, patients in the nitrous oxide group reported significantly lower visual analog scale for pain scores compared to the oxygen group (P = .026). The operating urologists' rating of tolerance of the procedure was better in the nitrous oxide group (P = .03). There were no differences in biopsy performance time. Complications were similarly low between the 2 groups. CONCLUSIONS: Patient-adjusted nitrous oxide at levels of 20% to 45% is a safe adjunct during transrectal prostate biopsy. Although there was not an observed difference in the primary end point of anxiety, nitrous oxide was associated with lower patient-reported pain scores.

How I Do It: Teaching holmium laser enucleation of the prostate (HoLEP).

Holmium laser enucleation of the prostate (HoLEP) is considered a size-independent technique to treat benign prostatic hyperplasia. This safe and effective procedure is increasingly being adopted in urology training programs worldwide, yet limited teaching strategies have been described. Endoscopic handling during HoLEP allows for a simultaneous interaction between the surgeon and trainee, facilitating a guided teaching strategy with increasing difficulty as experience grows. In this article, we describe our stepwise approach for teaching HoLEP as part of a structured surgical training curriculum. We also evaluate the association of our method with intraoperative efficiency parameters and immediate postoperative surgical outcomes of 200 HoLEP procedures.

Novel Education and Simulation Tools in Urologic Training.

PURPOSE OF REVIEW: Postgraduate medical training has evolved considerably from an emphasis on hands-on, autonomous learning to a paradigm where simulation technologies are used to introduce and augment certain skill sets. This review is intended to provide an update on surgical simulators and tools for urological trainee education. RECENT FINDINGS: We provide an overview of simulation platforms for robotics, endoscopy, and laparoscopic practice and training. In general, these simulators provide face, content, and construct validity. Various educational and evaluation tools have been adopted. Simulation platforms have been developed for technical and non-technical surgical skills, educational bootcamps, and tools for evaluation and feedback. While trainees find the opportunity to practice their skills beneficial, there may be difficulty with access due to cost and availability. Additionally, there is a need for more objective metrics demonstrating improvement in skill or patient outcome.

Delay from biopsy to radical prostatectomy influences the rate of adverse pathologic outcomes.

BACKGROUND: We sought to determine maximum wait times between biopsy diagnosis and surgery for localized prostate cancer, beyond which the rate of adverse pathologic outcomes is increased. METHODS: We retrospectively reviewed 4,610 patients undergoing radical prostatectomy between 1990 and 2011. Patients were stratified by biopsy Gleason score and PSA value. For each stratification, χ2 analysis was used to determine the smallest 15-day multiple of surgical delay (e.g., 15, 30, 45…180 days) for which adverse pathologic outcomes were significantly more likely after the time interval than before. Adverse outcomes were defined as positive surgical margins, upgrading from biopsy, upstaging, seminal vesicle invasion, or positive lymph nodes. RESULTS: Two thousand two hundred twelve patients met inclusion criteria. Median delay was 64 days (mean 76, SD 47). One thousand six hundred seventy-five (75.7%), 537 (24.3%), and 60 (2.7%) patients had delays of <=90, >90, and >180 days, respectively. Twenty-six percent were upgraded on final pathology and 23% were upstaged. The positive surgical margin rate was 24.2% and the positive lymph node rate was 1.1%. Significant increases in the proportion of adverse pathological outcomes were found beyond 75 days in the overall cohort (P = 0.03), 150 days for patients with Gleason <=6, and PSA 0-10 (P = 0.038), 60 days for patients with Gleason 7 and PSA >20 (P = 0.032), and 30 days for patients with Gleason 8-10 and PSA 11-20 (0.041). CONCLUSION: In low-risk disease, there is a considerable but not unlimited surgical delay which will not adversely impact the rate of adverse pathologic features found. In higher risk disease, this time period is considerably shorter.

Utilization and perioperative complications of laparoscopic cryoablation vs. robotic partial nephrectomy for localized renal tumors.

OBJECTIVE: To compare the utilization, perioperative complications and predictors of LCA versus RPN in the treatment of localized renal tumors. METHODS: From the Nationwide Inpatient Sample we identified patients undergoing RPN or LCA for the treatment of localized renal tumors from October 2008 through 2010. Patient and hospital-specific factors which predict postoperative complications and use of LCA were investigated. RESULTS: 14,275 patients with localized renal tumors were identified: 70.3% had RPN and 29.7% had LCA. LCA was more common in older patient and at hospitals without robotic consoles. No difference was identified in perioperative complications (0.2% vs. 0.2%), transfusion (5.1% vs. 6.2%), length of stay (2.9 vs. 3.0 days) or median cost ($41,753 vs. $44,618) between the groups, LCA vs. RPN. On multivariate analysis sicker patients were more likely to have LCA (OR 1.34, p=0.048) and sicker patients had greater postoperative complications (OR 3.30, p<0.001); LCA did not predict more complications (OR 1.63, p=0.138) and LCA was performed at hospitals without RCs (OR 0.02, p<0.001). Limitations include observational study design, inability to assess disease severity, operative time, or body mass index, which may affect patient selection and outcomes. CONCLUSIONS: More patients had RPN vs. LCA; surgical technique was not predictive of postoperative complications. As technology develops to treat localized renal tumors, it will be important to continue to track outcomes and costs for procedures including RPN and LCA.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

Conditional survival following radical cystectomy for urothelial carcinoma of the bladder.

INTRODUCTION: Traditional surveillance protocols do not adequately account for the decreasing risk of mortality over time in aggressive malignancies, such as bladder cancer. Rather, the risk of death depends on both the baseline risk of mortality and the time survived since treatment. We therefore evaluated the conditional survival of patients diagnosed with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). PATIENTS AND METHODS: We identified patients aged 18 to 75 with Charlson 0-1 and pTany pN0-3 cM0 UCB diagnosed from 2006 to 2015 in the National Cancer Database and treated with RC. The 2- and 5-year conditional overall survival (COS)-i.e., the probability of surviving an additional 2- or 5-years given a specified time survived since treatment-was estimated using the Kaplan-Meier method. Multivariable Cox regression models with landmark time analysis were used to evaluate the associations of baseline characteristics with OS over time. RESULTS: A total of 15,594 patients were included in the study. Median follow-up was 27.8 months. The 2- and 5-year COS for the overall cohort increased through 36 months follow-up and then plateaued. When stratified by pT and pN stage, the COS gain increased with higher pT and pN stage, demonstrating the greatest increase over time for patients with pTany N1-3 disease (5-year COS of 23% at baseline, 58% at 36-months, and 71% at 60-months). In multivariable Cox regression modeling, pT and pN stage were significantly associated with higher all-cause mortality at baseline (HR 3.27 for pT4, HR 2.57 for pT3 vs. ≤pT2; HR 2.26 for pN2-3, HR 1.77 for pN1 vs. pN0), but these associations were attenuated in magnitude with increasing landmark times of 36- and 60-months (HR 1.63 for pT4, HR 1.35 for pT3 vs. ≤pT2; HR 1.34 for pN2-3, HR 1.27 for pN1 vs. pN0). Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: Risk of death after RC varies with time elapsed since treatment and disease stage. Accordingly, stage-specific COS may be used to improve prognostication and surveillance protocols.

Disparities in the prevalence and management of high-risk non-muscle invasive bladder cancer.

OBJECTIVE: To evaluate the associations of socioeconomic characteristics with the management of non-muscle invasive bladder cancer (NMIBC). METHODS: We identified adult patients aged 18 to 89 years with Ta, T1, or Tis NMIBC in the NCDB. We then examined the associations of patient and socioeconomic characteristics with the guidelines-based management of high-risk NMIBC using multivariable logistic regression. RESULTS: 163,949 patients were included in the study cohort, including 64% with Ta, 32% with T1, and 4% with Tis disease. Among those diagnosed with bladder cancer, male (OR 1.24, 95%CI 1.21-1.27), uninsured (OR 1.10, 95%CI 1.01-1.19 vs. private), and non-White (OR 1.34, 95%CI 1.28-1.41 for Black; OR 1.10; 95%CI 1.03-1.18 for Other vs. White) patients were more likely to be diagnosed with high-risk disease, as well as patients from lower education level areas. Among those with high-risk NMIBC, patients who were older, non-White, Hispanic, uninsured or insured with Medicaid were less likely to receive guideline recommended intravesical BCG, while those residing in rural and higher education level areas were more likely to receive BCG. When examining non-guidelines based use of radiotherapy for HGT1 disease, older age (OR 1.06; 95% CI 1.04-1.07) and VA/Military insurance (OR 2.73; 95%CI 1.07, 6.98 vs. private) were associated with radiotherapy use. CONCLUSION: There are strong disparities in the prevalence and management of high-risk NMIBC. These observations highlight important targets for future strategies to reduce such healthcare disparities and provide more equitable bladder cancer treatment to patients.

Urothelial carcinoma of the bladder with isolated lymph node metastasis: Natural history and outcomes following surgical resection.

INTRODUCTION: Although pathologic lymph node involvement carries a poor prognosis in patients with urothelial carcinoma of the bladder (UCB), a subset of patients may demonstrate durable survival following surgical resection. To this end, there are limited contemporary data describing the natural history of UCB in patients with isolated lymph node involvement (cN0pN+) following radical cystectomy (RC) with pelvic lymph node dissection (PLND). We therefore utilized a large, nationwide oncology dataset to examine the natural history and outcomes of cN0 pN+ UCB after surgical resection. MATERIALS AND METHODS: We identified patients in the National Cancer Database (NCDB) with cN0 pN+ cM0 UCB from 2006 to 2015 treated with RC and PLND. The associations of baseline characteristics with all-cause mortality (ACM) were evaluated using Cox regression. RESULTS: A total of 2,884 patients formed the study cohort, including 42% with pN1 and 58% with pN2-3 disease. Of these, 606 (21%) received multiagent neoadjuvant chemotherapy, while 1,172 (41%) received postoperative adjuvant chemotherapy. A median of 15 (IQR 9-23) LNs were removed during PLND. The 5- and 7-year OS for the entire cohort were 20% and 17%, respectively. Compared to the overall cohort, patients surviving ≤5 years had lower pN stage (59% vs. 42% pN1) and lower pT stage (41% vs. 22% ≤pT2). On multivariable analysis, higher pT stage (HR 2.85, 95% CI 1.52-5.36 for pT3, HR 3.27, 95% CI 1.73-6.18 for pT4 vs. pT0), higher pN stage (HR 1.17, 95% CI 1.05-1.31 for pN2-3 vs. pN1), and increasing LN density (HR 2.37, 95% CI 1.88-2.99) were most strongly associated with increased ACM, while receipt of adjuvant chemotherapy (HR 0.61, 95% CI 0.55-0.68) was associated with reduced ACM. CONCLUSIONS: Although OS for patients with cN0 pN+ M0 UCB is poor, a subset of patients demonstrates durable long-term survival with 5- and 7-year OS of 20% and 17%, respectively. pT and pN stage represent important prognostic characteristics, while administration of adjuvant chemotherapy represents a potential therapeutic intervention associated with improved ACM.

Comparative Effectiveness of Magnetic Resonance Imaging-Ultrasound Fusion Versus In-bore Magnetic Resonance Imaging-targeted Prostate Biopsy.

OBJECTIVE: To examine the comparative effectiveness of magnetic resonance imaging-ultrasound (MRI-U/S) fusion biopsy and in-bore MRI-targeted biopsy. METHODS: We identified men aged 18-89 with a diagnosis of elevated prostate specific antigen (PSA) or Gleason 6 prostate cancer on active surveillance who underwent MRI-U/S fusion prostate biopsy (12-core + targeted) in the office or in-bore MRI-targeted biopsy (MRI-IB; targeted only). The cancer detection rate (CDR; Gleason 6-10) and clinically significant CDR (csCDR; Gleason 7-10) were compared across biopsy techniques, adjusted for patient and radiographic features. RESULTS: A total of 280 patients (346 lesions) were included, of whom 23.9% were on active surveillance for Gleason 6 prostate cancer. In the per-patient analyses, there was no statistically significant difference in adjusted overall CDR (64.1% vs 54.2%; P = .24) or csCDR (36.5% vs 37.9%; P = .85) between MRI-U/S and MRI-IB biopsy. In the per-lesion analyses, there was no statistically significant difference in adjusted overall CDR (45.7% vs 50.1%; P = .49) between MRI-U/S and MRI-IB biopsy, but MRI-IB biopsy was associated with a higher csCDR than MRI-U/S biopsy (32.8% vs 21.4%; P = .02). CONCLUSION: We observed no statistically significant differences in cancer detection rates between MRI-U/S fusion biopsy and MRI-IB biopsy in per-patient analyses. However, MRI-IB biopsy was associated with higher csCDR when considering targeted biopsy cores only. These results suggest that systematic cores should be obtained when performing MRI-U/S fusion biopsy.

Predictors of locally advanced and metastatic disease in patients with small renal masses.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There is a small cohort of patients who have small renal masses with metastatic potential, yet risk factors for having this more aggressive disease are largely unknown. In a large sampling of the US population, older patients and men were more likely to have small renal masses at an advanced stage. OBJECTIVES: To assess the prevalence metastatic and locally advanced renal cell carcinoma (RCC) in the US population with small renal masses (SRMs). To determine what patient and tumour characteristics predict having more advanced SRMs. PATIENTS AND METHODS: Using the Surveillance, Epidemiology and End Results (SEER) registry, we identified 14, 962 patients who were diagnosed between 1988 and 2007 with RCC ≤ 3 cm in size. Patients were separated by stage into those with metastatic, locally advanced and localized disease. Differences in baseline characteristics between patients in these three groups were assessed. After controlling for age, sex, grade, tumour size and year of surgery, a logistic regression analysis was performed to determine the likelihood of having non-localized disease. RESULTS: In the SEER cohort, 13, 574 (90.7%) patients with RCC ≤ 3 cm in size were diagnosed with localized disease, 938 (6.3%) patients had invasion beyond the kidney into regional lymph nodes or nearby organs, and 450 (3.0%) patients had distant metastasis. Patients with metastasis were older (65.9 years) compared to those with localized disease (59.5 years) (P < 0.001). Independent preoperative predictors of having more aggressive disease at diagnosis (locally advanced/metastatic) included older age, particularly age >70 years (odds ratio, OR, 2.42; 95% confidence interval, CI, 2.03-2.88), male sex (OR, 1.50; 95% CI, 1.33-1.70) and tumour size >2.5 (OR, 1.41; 95% CI, 1.25-1.58). CONCLUSIONS: A small subset (3%) of patients in the USA with RCC ≤ 3 cm in size have distant metastasis. Older patients, men and those with tumours 2.5-3.0 cm in size have a greater probability of presenting with non-localized disease . Clinicians should be aware that there is a risk of metastases in patients with SRMs and also familiarize themselves with the characteristics associated with advanced disease.

Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis.

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high-risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes. OBJECTIVE: • To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: • We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution. • Clinical and pathological features were compared between men undergoing RP ≤ 60, 61-90 and >90 days from the time of prostate biopsy. • A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)-free rates were assessed using the Kaplan-Meier method. RESULTS: • Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of ≤ 60, 61-90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery. • The 5-year survival rate was similar among the three groups (78-85%, P= 0.11). • In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African-American race were all at higher risk for developing BCR. • A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model. CONCLUSIONS: • A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR-free survival. • Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes.

Adjuvant chemotherapy versus observation following radical cystectomy for locally advanced urothelial carcinoma of the bladder.

BACKGROUND: The role of adjuvant chemotherapy (AC) in patients with locally advanced bladder cancer following radical cystectomy (RC) remains uncertain, with contemporary clinical trials underpowered and closed early due to low accrual. OBJECTIVE: To conduct observational analyses designed to emulate a completed randomized trial of AC in patients with locally advanced bladder cancer. DESIGN, SETTINGS, AND PARTICIPANTS: Based on EORTC 30994 eligibility criteria, we identified adult patients aged 35 to 75 with pT3/pT4 Nany M0 or Tany pN1-3 M0, R0 urothelial carcinoma of the bladder treated with RC and lymphadenectomy from 2006 to 2015 in the National Cancer Database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A propensity score for receipt of AC within 3 months of RC was estimated, and the associations of AC with overall survival were evaluated after reweighting by stabilized inverse probability of treatment weights. RESULTS: Of the 2,416 patients who met inclusion criteria, 945 (39%) received AC after RC. After propensity score adjustment, baseline characteristics were well-balanced. Median follow-up was 26.0 months. After IPW-reweighting, overall survival was 43% vs. 36% at 5-years and 34% vs. 24% at 10-years, among those who did and did not receive AC, respectively (P < 0.01). In IPW-adjusted Cox regression models, AC was associated with improved all-cause mortality (HR 0.71; 95% CI 0.63-0.81; P < 0.01). Estimates were overall consistent in analyses that examined heterogeneity of treatment effects. Limitations include unmeasured confounding, selection bias, and lack of baseline renal function data. CONCLUSION: In observational analyses designed to emulate EORTC 30994, AC was associated with improved overall survival compared to observation after RC. Results were consistent across baseline patient and tumor characteristics.

Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy.

BACKGROUND: The optimal management of node-positive (pN1) prostate cancer following radical prostatectomy (RP) remains uncertain. Despite randomized evidence, utilization of immediate, life-long androgen deprivation therapy (ADT) remains poor, and recent trials of early salvage radiotherapy included only a minority of pN1 patients. We therefore emulated a hypothetical pragmatic trial of adjuvant radiotherapy versus observation in men with pN1 prostate cancer. METHODS: Using the RADICALS-RT trial to inform the design of a hypothetical trial, we identified men aged 50-69 years with pT2-3 Rany pN1 M0, pre-treatment PSA < 50 ng/mL prostate cancer in the NCDB from 2006 to 2015 treated with 60-72 Gy of adjuvant RT (aRT) ± ADT within 26 weeks of RP or observation. After estimating a propensity score for receipt of aRT, we estimated absolute and relative treatment effects using stabilized inverse probability of treatment (sIPW) re-weighting. RESULTS: In total, 3510 patients were included in the study, of whom 587 (17%) received aRT (73% with concurrent ADT). Median follow-up was 40.0 -months, during which 333 deaths occurred. After sIPW re-weighting, baseline characteristics were well-balanced. Adjusted overall survival (OS) was 93% versus 89% at 5-years and 82% versus 79% at 7-years for aRT versus observation (p = 0.11). In IPW-reweighted Cox regression, aRT was associated with a lower risk of all-cause mortality (ACM) than observation, but this did not reach statistical significance (HR 0.70 p = 0.06). In analyses examining heterogeneity of treatment effects, aRT was associated with improved ACM only for men with Gleason 8-10 disease (HR 0.59, p = 0.01), ≥2 positive LNs (HR 0.49, p = 0.04 for 2 positive LNs; HR 0.42, p = 0.01 for ≥3 positive LNs), or negative surgical margins (HR 0.50, p = 0.02). CONCLUSIONS: In observational analyses designed to emulate a hypothetical target trial of aRT versus observation in pN1 prostate cancer, aRT was associated with improved OS only for men with Gleason 8-10 disease, ≥2 positive LNs, or negative surgical margins.

Adjuvant Chemotherapy Plus Radiotherapy versus Chemotherapy Alone for Locally Advanced Bladder Cancer after Radical Cystectomy.

BACKGROUND: Survival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT). OBJECTIVE: We examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC. METHODS: Using a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18-79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006-2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression. RESULTS: 1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; p < 0.01), positive surgical margins (44% vs 17%; p < 0.01), and be treated at a non-academic facility (75% vs 53%; p < 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone (p = 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone (p = 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82-1.51). CONCLUSIONS: Although infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.

Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder.

BACKGROUND: The comparative effectiveness of radical cystectomy (RC) and trimodality therapy (TMT) for muscle-invasive bladder cancer remains uncertain, as no randomized data exist. A phase 3 trial (SPARE) was attempted in the UK, however, was deemed infeasible and closed. OBJECTIVE: To emulate the SPARE trial using observational data. DESIGN, SETTING, AND PARTICIPANTS: We identified patients aged 40 to 79 with cT2-3cN0cM0 urothelial carcinoma of the bladder diagnosed from 2006 to 2015 who were treated with multiagent neoadjuvant chemotherapy + RC with lymphadenectomy (RC arm) or multiagent chemotherapy + 3D conformal radiotherapy to the bladder (TMT arm) in the National Cancer Database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was overall survival (OS). We fit a flexible logistic regression model for treatment to estimate the propensity score, and then used inverse probability of treatment weights to evaluate the associations of treatment group with OS. RESULTS AND LIMITATIONS: A total of 2,048 patients were included, of whom 1,812 underwent RC and 236 underwent TMT. Median follow-up was 29.0 months. After propensity score adjustment, compared to TMT, RC was not associated with a statistically significant difference in OS (HR 0.87; 95% CI 0.64-1.19; P = 0.40). When examining heterogeneity of treatment effects, RC appeared to be associated with improved OS only for patients with cT3 disease. Similar results were observed in sensitivity analyses. Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: In observational analyses designed to emulate the SPARE trial, there was no statistically significant difference in OS between RC and TMT. Heterogeneity of treatment effects suggested improved survival with RC only for cT3 disease.

Testicular symmetry and adolescent varicocele--does it need followup?

PURPOSE: Appropriate management for adolescent varicocele with testicular symmetry is rarely discussed. We examined the natural history of varicocele in patients presenting with testicular symmetry to achieve better understanding of the clinical course. MATERIALS AND METHODS: Our varicocele registry was queried for adolescent boys who presented with varicocele in association with less than 15% testicular asymmetry and who underwent at least 1 testicular asymmetry assessment 12 or more months later. Patients were stratified into 2 groups based on an initial testicular asymmetry measurement of less than 10% vs 10.0% to 14.9%. Logistic regression modeling was used to analyze the association of Tanner stage, varicocele grade, peak retrograde flow and maximum vein diameter at presentation with increased testicular asymmetry at followup. Kaplan-Meier methodology was applied to compare testicular asymmetry progression rates. RESULTS: We identified 89 adolescents, of whom 52 (58.4%) and 37 (41.6%) presented with less than 10.0% and 10.0% to 14.9% testicular asymmetry, respectively. Of the patients 37 (41.6%) showed testicular asymmetry progression at a median 18-month followup. The overall 3-year testicular asymmetry progression-free rate was 48% while in patients with peak retrograde flow 30 cm per second or greater it was 23%. On multivariate analysis controlled for age, Tanner stage and varicocele grade a peak retrograde flow of 30 cm per second or greater was associated with worsening testicular asymmetry (OR 4.87, 95% CI 1.6-8.0). CONCLUSIONS: Adolescents with varicocele and less than 15% testicular asymmetry are at risk for asymmetry during followup. Those with peak retrograde flow 30 cm per second or greater are at increased risk for early asymmetry while those with peak retrograde flow less than 30 cm per second may still show asymmetry but tend to do so after longer followup.

Post-percutaneous nephrolithotomy systemic inflammatory response: a prospective analysis of preoperative urine, renal pelvic urine and stone cultures.

PURPOSE: Prior studies suggest that renal pelvic urine culture is a more accurate predictor of urosepsis. We prospectively determined the correlation between preoperative bladder urine cultures, intraoperative renal pelvis cultures and stone cultures in patients undergoing percutaneous nephrolithotomy. We also examined post-procedure risk factors for systemic inflammatory response syndrome. MATERIALS AND METHODS: From February 2009 to February 2011 urine samples from the bladder and renal pelvis were collected from patients undergoing percutaneous nephrolithotomy. Extracted stones were also sent for culture analysis. Postoperatively patients were closely monitored for any signs of systemic inflammatory response syndrome. The concordance of urine and stone cultures across different sites was examined. Regression analysis was done to identify clinical variables associated with systemic inflammatory response syndrome. RESULTS: A total of 204 percutaneous nephrolithotomies were done in 198 patients, of whom 20 (9.8%) had evidence of systemic inflammatory response syndrome postoperatively, including 6 (30%) requiring intensive care. The concordance among stone, renal pelvic and preoperative cultures was 64% to 75% with the highest concordance between renal pelvic urine and stone cultures. In a multivariate model multiple access tracts and a stone burden of 10 cm(2) or greater were significant predictors of systemic inflammatory response syndrome postoperatively. CONCLUSIONS: Even appropriately treated preoperative urinary infections may not prevent infected urine at percutaneous nephrolithotomy. Renal pelvic urine and stone cultures may be the only way to identify the causative organism and direct antimicrobial therapy. We recommend collecting pelvic urine and stone cultures to identify the offending organism in patients at risk for sepsis, particularly those with a large stone burden requiring multiple access tracts.

Accuracy of the Kattan nomogram across prostate cancer risk-groups.

OBJECTIVE: • To investigate the predictive ability of nomograms at the extremes of preoperative clinical parameters by examining the predictive ability across all prostate cancer risk groups. PATIENTS AND METHODS: • The Columbia University Urologic Oncology Database was reviewed: 3663 patients underwent radical prostatectomy from 1988 to 2008. Patients who had received neoadjuvant or adjuvant therapy, or had insufficient clinical parameters for estimation of 5-year progression-free probability using the preoperative Kattan nomogram were excluded. • A total of 1877 patients were included and stratified by D'Amico risk criteria. Mean estimated nomogram progression rates were compared with actuarial Kaplan-Meier survival statistics. • A regression model to predict progression-free survival was fitted with estimated nomogram score and concordance indices were calculated for the entire model and subsequently for each risk group. RESULTS: • Of 1877 patients, 857 (45.6%) were low risk, 704 (37.5%) were intermediate risk, and 316 (16.8%) were high risk by D'Amico criteria. • Mean estimated nomogram survival and actuarial Kaplan-Meier survival at 5 years were 90.5% and 92.2% (95% CI 89.2-94.3) for low-risk, 76.7% and 77.8% (73.3-81.7) for intermediate-risk, and 65.8% and 60.4% (52.0-67.7) for high-risk groups, respectively. Using nomogram score in the regression model, the c-index for the full model was 0.61. • For low-, intermediate- and high-risk patients independently the c-index was 0.60, 0.59 and 0.57, respectively. When low-, intermediate- and high-risk patients were independently removed from the model the c-index was 0.64, 0.65 and 0.55, respectively. • The c-index for the full model using the categorical nomogram risk scores was 0.67. Similar to the D'Amico model, the c-index improved to 0.69 when intermediate-risk patients were removed from the model. CONCLUSIONS: • The study confirms the ability of preoperative nomograms to accurately predict actuarial survival across all risk groups. • The predictive ability of the nomogram varies by risk group, yet even at the extremes of high-risk and low-risk prostate cancer the nomogram accurately predicts outcome.

The impact of pretreatment PSA on risk stratification in men with Gleason 6 prostate cancer: Implications for active surveillance.

BACKGROUND: There are limited data to support the safety of active surveillance in men with favorable-intermediate risk prostate cancer due only to a prostate specific antigen (PSA) above 10 ng/ml. We therefore evaluated the impact of pretreatment PSA on risk-stratification in men with Gleason 6 prostate cancer. METHODS: We identified men aged 18 to 75 with cT1-2cN0cM0, pre-treatment PSA < 20 ng/ml, Gleason 6 prostate cancer diagnosed from 2010 to 2016 in the National Cancer Database who underwent radical prostatectomy. The associations of patient and disease features with Gleason score upgrading or adverse pathologic features at prostatectomy were evaluated using logistic regression. To evaluate for non linear relationships between PSA and each outcome, we examined predicted marginal event rates standardized for baseline characteristics with PSA modeled using restricted cubic splines RESULTS: A total of 75,566 patients were included in the cohort. In unadjusted analyses, patients with pretreatment PSA ≥ 10 ng/ml had higher rates of Gleason core upgrading (58.8% vs. 47.9%; P< 0.001) and adverse pathologic features (19.7% vs. 10.0%; P< 0.001) compared to patients with PSA < 10 ng/ml. In multivariable analyses, PSA ≥ 10 ng/ml was associated with statistically significantly increased risks of Gleason score upgrading (OR 1.47;95%CI 1.39 - 1.55) and adverse pathologic features (OR 2.15;95%CI 2.01 - 2.30). When modeled as a non linear continuous covariate, PSA was associated with increased adjusted rates of Gleason score upgrading and adverse pathologic features without a clear dichotomization at a threshold of 10 ng/ml. CONCLUSION: Higher pretreatment PSA was independently associated with increased risks of Gleason score upgrading and adverse pathologic features at prostatectomy. Flexible modeling of the relationship between PSA and each outcome did not support dichotomization at a threshold of 10 ng/ml. These results can be used to improve patient risk-stratification for active surveillance.