Neighborhood Socioeconomic Disadvantage Associated With Increased 90-Day Mortality Following Radical Cystectomy.

OBJECTIVE: To examine relationships between neighborhood socioeconomic disadvantage and outcomes following radical cystectomy (RC). MATERIALS AND METHODS: A retrospective single institution study of consecutive RCs performed for bladder cancer between 2011 and 2019. Major complications, mortality and survival outcomes were compared using Cochran-Armitage or Kruskal-Wallis tests. Cox proportional hazards models were used for time-to-event analyses. RESULTS: A total of 906 patients were included in analysis. Overall 90-day mortality was 2.98% (27/906). Ninety-day mortality rates observed in the least (first) and most (fourth) disadvantaged ADI quartiles were 0% (0/115) and 6.5% (12/185), respectively. Patients from the fourth quartile demonstrated worse overall survival and recurrence free survival than those in the first quartile. ADI quartile was positively associated with muscle invasive (P = .0006) and node positive (P = .042) disease. ADI percentile was an independent predictor for 90-day mortality (adjusted OR: 1.022, CI: 1.004-1.04, P = .015). CONCLUSION: Higher rates of mortality and worse oncologic outcomes were observed for patients residing in the most disadvantaged quartile. ADI was associated with higher likelihood of 90-day mortality and may therefore be useful in patient counseling, risk stratification, and post-discharge management.

Uretero-Enteric Anastomotic Stricture Following Radical Cystectomy: A Comparison of Open, Robotic Extracorporeal, and Robotic Intracorporeal Approaches.

OBJECTIVES: To compare the incidence of benign uretero-enteric anastomotic strictures between open cystectomy, robotic cystectomy with extracorporeal urinary diversion, and robotic cystectomy with intracorporeal urinary diversion. The effect of surgeon learning curve on stricture incidence following intracorporeal diversion was investigated as a secondary outcome. PATIENTS AND METHODS: Patients who underwent radical cystectomy at an academic hospital between 2011 and 2018 were retrospectively reviewed. The primary outcome, incidence of anastomotic stricture over time, was assessed by a multivariable Cox proportional hazards regression. A Cox regression model adjusting for sequential case number in a surgeon's experience was used to assess intracorporeal learning curve. RESULTS: Nine hundred sixty-eight patients were included: 279 open, 382 robotic extracorporeal, and 307 robotic intracorporeal. Benign stricture incidence was 11.3% overall: 26 (9.3%) after open, 43 (11.3%) after robotic extracorporeal, and 40 (13.0%) after robotic intracorporeal. An intracorporeal approach was associated with anastomotic stricture on multivariable analysis (HR 1.66; P = .05). After 75 intracorporeal cases, stricture incidence declined from 17.5% to 4.9%. Higher sequential case volume was independently associated with reduced stricture incidence (Hazard Ratio per 10 cases: 0.90; P = .02). CONCLUSION: An intracorporeal approach to urinary reconstruction following robotic radical cystectomy was associated with an increased risk of benign uretero-enteric anastomotic stricture. In surgeons' early experience with intracorporeal diversion the difference in stricture incidence was more pronounced compared to alternative approaches; however, increased intracorporeal case volume was associated with a decline in stricture incidence leading to a modest difference between the 3 surgical approaches overall.

Heterogenous Dose-escalated Prostate Stereotactic Body Radiation Therapy for All Risk Prostate Cancer: Quality of Life and Clinical Outcomes of an Institutional Pilot Study.

OBJECTIVES: Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious. MATERIALS AND METHODS: Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx. RESULTS: Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%. CONCLUSIONS: Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.

Older Age at Diagnosis and Initial Disease Volume Predict Grade Reclassification Risk on Confirmatory Biopsy in Patients Considered for Active Surveillance.

OBJECTIVE: To identify which active surveillance candidates benefit most from confirmatory biopsies to exclude grade underclassification. MATERIALS AND METHODS: This observational study includes 556 men diagnosed between 2002 and 2015 with Gleason 3 + 3 (GG1) disease on initial diagnostic biopsy, of whom 406 received a confirmatory biopsy within 12 months for active surveillance. Multivariable logistic regression analysis was performed to determine clinicopathologic features associated with Gleason 7 or higher (GG2+) on a confirmatory biopsy. Regression tree analysis was employed to stratify patients into select risk groups. RESULTS: Eighty-five of 406 patients (20.9%) with initially GG1 disease were reclassified to GG2+ on a confirmatory biopsy. On multivariable analysis, increasing age (per year odds ratio 1.07; 95% confidence interval 1.02-1.12; P <.01) and more positive cores at diagnosis (per core, odds ratio 1.37, 95% confidence interval 1.09-1.72; P <.01) were significantly associated with reclassification, independent of prostate volume, clinical stage, initial PSA, or confirmatory biopsy type (including magnetic resonance imaging-targeted approaches or transrectal saturation random sampling). Recursive partitioning demonstrated that age over 73 and 5 or more positive cores were factors associated with the greatest reclassification risk. CONCLUSION: In our cohort, both advancing age and additional positive cores were associated with increased odds of reclassification to GG2+ on confirmatory biopsy. In men over age 73 or with 5 or more positive cores, a repeat biopsy within 12 months may be particularly beneficial to minimize tumor grade underclassification.

Principles and practice of high-dose rate penile brachytherapy: Planning and delivery techniques.

PURPOSE: To allow for organ preservation, high-dose rate (HDR) brachytherapy may be used in the treatment of localized penile cancer. Penile cancer is a rare malignancy that accounts for <1% of cancers in men in the United States. The standard treatment for localized disease is partial amputation of the penis. However, patients with T1b or T2 disease <4 cm in maximum dimension and confined to the glans penis may be treated with brachytherapy as an organ-sparing approach. Previous works have described the technique involved for low-dose rate brachytherapy; however, we detail the techniques involved with HDR brachytherapy. METHODS AND MATERIALS: Circumcision should precede brachytherapy. Interstitial brachytherapy needles are placed in the operating room under general anesthesia with the goal to allow for appropriate target coverage. Target definition is done via computed tomography-based simulation and planning. Radiation is delivered using a prescription dose of 3840 cGy in 12 fractions twice daily over a course of 6 days. RESULTS: Acute toxicities peak upon completion of the radiation therapy and may include dermatitis, sterile urethritis, and adhesions in the urethra. These toxicities are reversible and generally take 2 to 3 months to heal. The two most common and significant late complications of radiation therapy for penile cancer are soft tissue necrosis and meatal stenosis. An increased risk of necrosis has been reported with T3 tumors and higher-volume implants (>30 cm3). Erectile function is generally maintained because the erectile tissues including the penile shaft and corpora have not been irradiated. CONCLUSIONS: Organ preservation is feasible using HDR brachytherapy with favorable acute and late toxicities.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance.

OBJECTIVE: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling. RESULTS: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.

PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes.

PURPOSE: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. RESULTS: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. CONCLUSIONS: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

A multi-institutional evaluation of active surveillance for low risk prostate cancer.

PURPOSE: For select men with low risk prostate cancer active surveillance is more often being considered a management strategy. In a multicenter retrospective study we evaluated the actuarial rates and predictors of remaining on active surveillance, the incidence of cancer progression and the pathological findings of delayed radical prostatectomy. MATERIALS AND METHODS: A cohort of 262 men from 4 institutions met the inclusion criteria of age 75 years or younger, prostate specific antigen 10 ng/ml or less, clinical stage T1-T2a, biopsy Gleason sum 6 or less, 3 or less positive cores at diagnostic biopsy, repeat biopsy before active surveillance and no treatment for 6 months following the repeat biopsy. Active surveillance started on the date of the second biopsy. Actuarial rates of remaining on active surveillance were calculated and univariate Cox regression was used to assess predictors of discontinuing active surveillance. RESULTS: With a median followup of 29 months 43 patients ultimately received active treatment. The 2 and 5-year probabilities of remaining on active surveillance were 91% and 75%, respectively. Patients with cancer on the second biopsy (HR 2.23, 95% CI 1.23-4.06, p = 0.007) and a higher number of cancerous cores from the 2 biopsies combined (p = 0.002) were more likely to undergo treatment. Age, prostate specific antigen, clinical stage, prostate volume and number of total biopsy cores sampled were not predictive of outcome. Skeletal metastases developed in 1 patient 38 months after starting active surveillance. Of the 43 patients undergoing delayed treatment 41 (95%) are without disease progression at a median of 23 months following treatment. CONCLUSIONS: With a median followup of 29 months active surveillance for select patients appears to be safe and associated with a low risk of systemic progression. Cancer at restaging biopsy and a higher total number of cancerous cores are associated with a lower likelihood of remaining on active surveillance. A restaging biopsy should be strongly considered to finalize eligibility for active surveillance.

Optimal prostate biopsy regimen.

The prostate-specific antigen (PSA) era has increased the rates of prostate cancer detection and treatment, while reducing the risk of death from prostate cancer in the US. Image-guided prostate biopsy techniques have led to stage migration and the detection and treatment of lower risk prostate cancers. Improved techniques with laterally directed biopsy, office-based saturation biopsy, and transperineal biopsy under anesthesia have increased the detection rates of smaller volume tumors. Improved detection of ever-smaller tumors assists the clinician in determining what treatment is most appropriate for the patient, including the use of active surveillance and focal therapy. Furthermore, the detection of small volume, high grade cancers may widen the latency interval in which a clinically significant tumor may be detectable and curable.

Early infectious complications with transponder placement for external beam radiation therapy for prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Little has been published related to transponders per se, but a number of studies relating to prostate biopsy-related infections and the increased incidence of quinolone-resistant Escherichia coli have been published. The study alerts the practising urologist to the risk of quinolone-resistant E. coli in the setting of transrectally placed transponders. Furthermore, it proposes an antibiotic regimen that should reduce this risk. OBJECTIVE: To report our series of early infectious complications after placement of Calypso(®) transponders (Calypso Medical, Seattle, WA, USA) into the prostate. PATIENTS AND METHODS: Between February 2008 and October 2010, 50 consecutive patients underwent placement of Calypso(®) transponders into the prostate. Patients were administered ciprofloxacin 500 mg every 12 h, starting the night before the procedure and for 2 days after the procedure. Data were collected via chart review, and complications were classified according to the Clavien classification system. RESULTS: Of the 50 patients undergoing the procedure, five (10%) developed infectious complications, and three (6%) developed a grade II complication with a UTI requiring antibiotic therapy. One patient (2%) developed a grade IIIb complication with an epidural abscess and osteomyelitis of the lumbar vertebrae requiring open debridement and a lumbar fusion. One patient (2%) developed a prostatic abscess with methicillin-resistant Staphylococcus aureus and subsequently died of an unrelated lower GI bleed. In 4/50 patients (8%), a culture confirmed the responsible bacteria, of which three cases were quinolone-resistant Escherichia coli. CONCLUSION: As with prostate biopsy, the emergence of quinolone-resistant E. coli remains a challenging infectious complication with transrectal prostate procedures. We propose an alternative strategy of double antibiotic coverage with one dose of oral ciprofloxacin 500 mg and gentamicin 80 mg i.m. before this procedure.

Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study 9109.

OBJECTIVE: To update the results with 10-year data of a phase II prospective trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer (SWOG 9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain. MATERIALS AND METHODS: Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs T4 and by volume of disease (bulky >4 cm and nonbulky ≤ 4 cm). RESULTS: Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate-specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of ≥ 7. Among 41 patients last known to be alive, median follow-up is 10.6 years (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%) or died without progression (8/55, 15%) for a 10-year progression-free survival (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median survival has not been reached. The 10-year overall survival (OS) estimate is 68% (95% CI 56-80). CONCLUSIONS: In this small, prospective phase II study, neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments. This approach is feasible and may be an alternative to a strategy of combined radiation and ADT.

Utility of percent free prostate-specific antigen in repeat prostate biopsy.

OBJECTIVES: To assess the utility of the percent free prostate-specific antigen (%fPSA) for the prediction of prostate cancer in men undergoing repeat biopsy. METHODS: A retrospective review was performed of 1037 patients in an institutional review board-approved repeat prostate biopsy database. A total of 617 patients who underwent 683 biopsies had all their data available for analysis. The patients were categorized as having undergone 1 repeat biopsy or >1 repeat biopsy. RESULTS: The overall cancer detection rate was 27% and 22% in men who underwent 1 and >1 repeat biopsy, respectively. The area under the receiver operating characteristic curve for the %fPSA was 0.65 for men who underwent 1 repeat biopsy. Multivariate analysis demonstrated that a positive family history, decreasing %fPSA, and presence of high-grade intraepithelial neoplasia and/or atypical small acinar proliferation predicted for cancer. The univariate odds ratio for every 5% decrease in the %fPSA was 1.5 (95% confidence interval 1.2-1.7). The performance of %fPSA was further improved in men who underwent >1 repeat biopsy, with an area under the curve of 0.72. In men who underwent >1 repeat biopsy, multivariate analysis showed that a decreasing %fPSA, >20 cores removed, and high-grade intraepithelial neoplasia predicted for cancer. The univariate odds ratio for every 5% decrease in the %fPSA was 1.8 (95% confidence interval 1.4-2.3). A %fPSA cutoff of 10% achieved 90% and 91% specificity in the 1 repeat biopsy and >1 repeat biopsy groups, respectively. CONCLUSIONS: %fPSA is useful in predicting for prostate cancer in the repeat biopsy population, particularly for those who have undergone multiple repeat biopsies. A persistently low %fPSA should prompt additional investigation in these men.

A practical guide to prostate cancer diagnosis and management.

Screening, diagnosis, and management of prostate cancer can be complicated, with no clear consensus about key issues. We present our approach, which reflects the guidelines of the American Urological Association (AUA).

Avoiding androgen deprivation therapy in men with high-risk prostate cancer: the role of radical prostatectomy as initial treatment.

OBJECTIVE: To examine the ability of surgery as initial management in avoiding androgen deprivation therapy (ADT) in patients with high-risk localized prostate cancer. MATERIALS AND METHODS: A total of 267 men were identified from a cohort of patients treated by radical prostatectomy (RP) between January 1998 and June 2004. Patients were included if they presented with clinical stage ≥T2b and/or prostate-specific antigen (PSA) ≥15 ng/mL, and/or Gleason score ≥8. Information on biochemical recurrence, distant metastasis, cancer-specific survival, and use of ADT was obtained from a prospectively maintained database. RESULTS: The median follow-up was 6.7 years (range, 1-146 months). Biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were observed in 112 (42%), 28 (10%), and 15 (6%) patients, respectively. Salvage treatment was performed in 95 (85%) of 112 patients with BCR. Only 71 (27%) of 267 men were subjected to ADT. Overall, 8-year probabilities of freedom from BCR, DM, PCSM, and ADT were 46% (95% CI, 38-54), 87% (95% CI, 84-90), 93% (95% CI, 91-95), and 71% (95% CI, 65-77), respectively. CONCLUSIONS: RP provides excellent long-term clinical outcomes for patients with high-risk localized prostate cancer and avoids the use of ADT in approximately 70% of these patients.