Michael Porter

DISEASE-FREE AND OVERALL SURVIVAL AFTER CRYOSURGICAL MONOTHERAPY FOR CLINICAL STAGES B AND C CARCINOMA OF THE PROSTATE: A 20-YEAR FOLLOWUP

PURPOSEnWe attempt to provide insight into the historical efficacy of cryosurgical monotherapy for prostate carcinoma through a single institution, retrospective, long-term followup.nnnMATERIALS AND METHODSnFrom 1973 to 1977, 66 men underwent cryosurgical monotherapy for prostate carcinoma. Patient charts were reviewed to determine age, clinical stage, tumor grade, and progression-free, overall and cause specific survival status.nnnRESULTSnOf 51 patients 47 to 81 years old (mean age 67.2) with clinically localized carcinoma 11 had clinical stage B and 40 had stage C disease. Tumor grade was well differentiated in 11 cases, moderately differentiated in 26, poorly differentiated in 11 and undetermined in 3. Recurrence was documented in 40 of the 51 men (78.4%) as local in 34 and unspecified in 6. Following recurrence all patients were treated with adjuvant therapy. All but 2 patients were followed until death with a mean followup of 93.7 months. Of the 51 men 24 (47.1%) died of disease and 17 (33.3%) died of an unspecified cause. Kaplan-Meier analysis demonstrated median overall progression-free survival of 34 months and median overall survival of 75 months. Median progression-free survival by grade was 34 months for well differentiated, 36 for moderately differentiated and 14 for poorly differentiated disease (p = 0.0288), and 57 for stage B and 30 for stage C disease (p = 0.0377). Median overall survival by grade was 114 months for well differentiated, 80 for moderately differentiated and 82 for poorly differentiated disease (p = 0.4437), and 60 months for stage B and 78.5 for stage C disease (p = 0.4915).nnnCONCLUSIONSnAs performed in this series cryosurgery was poorly effective for local control of prostatic carcinoma. Stage and grade correlated with the duration of tumor response but not with overall survival.

Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer

Background:Obesity is consistently linked with prostate cancer (PCa) recurrence and mortality, though the mechanism is unknown. Impaired glucose regulation, which is common among obese individuals, has been hypothesized as a potential mechanism for PCa tumor growth. In this study, we explore the relationship between serum glucose at time of treatment and risk of PCa recurrence following initial therapy.Methods:The study group comprised 1734 men treated with radical prostatectomy (RP) or radiation therapy (RT) for localized PCa between 2001–2010. Serum glucose levels closest to date of diagnosis were determined. PCa recurrence was determined based on PSA progression (nadir PSA+2 for RT; PSA⩾0.2 for RP) or secondary therapy. Multivariate Cox regression was performed to determine whether glucose level was associated with biochemical recurrence after adjusting for age, race, body mass index, comorbidity, diagnosis of diabetes, Gleason Sum, PSA, treatment and treatment year.Results:Recurrence was identified in 16% of men over a mean follow-up period of 41 months (range 1–121 months). Those with elevated glucose (⩾100u2009mg/dl) had a 50% increased risk of recurrence (HR 1.5, 95% CI: 1.1–2.0) compared with those with a normal glucose level (<100u2009mg/dl). This effect was seen in both those undergoing RP (HR 1.9, 95% CI: 1.0–3.6) and those treated with RT (HR 1.4, 95% CI: 1.0–2.0).Conclusions:Glucose levels at the time of PCa diagnosis are an independent predictor of PCa recurrence for men undergoing treatment for localized disease.

Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort

BACKGROUND:Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment.METHODS:Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2u2009ngu2009ml−1 (radiation) or PSA⩾0.2u2009ngu2009ml−1 (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85u2009mmu2009Hg, fasting blood glucose ⩾100u2009mgu2009dl−1, waist circumference >102u2009cm, high-density lipoprotein <40u2009mgu2009dl−1, triglycerides ⩾150u2009mgu2009dl−1). Closely related abnormality in low-density lipoprotein (LDL; >130u2009mgu2009dl−1) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment.RESULTS:Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1–120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62).CONCLUSIONS:PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

Pathologic response rates between gemcitabine-cisplatin (GC) and methotrexate, vinblastine, doxorubicin hydrochloride, and cisplatin (MVAC) neoadjuvant chemotherapy in muscle-invasive urothelial cell carcinoma of the bladder.

267 Background: Neoadjuvant chemotherapy for muscle invasive urothelial carcinoma (UC) of the bladder is associated with higher rates of pathologic complete response (CR) and improved disease-specific survival compared to those treated with radical cystectomy (RC) alone. Two standard regimens used are (1) gemcitabine and cisplatin (GC); and (2) methotrexate, vinblastine, adriamycin, and cisplatin (MVAC), with debate on whether there is a difference in clinical efficacy. In this analysis, we compare the pathologic outcomes at cystectomy between neoadjuvant GC and MVAC treatment.nnnMETHODSnData was retrospectively collected on patients with T2-T4 UC of the bladder who underwent RC between Sept 2003 and December 2011 at the University of Washington. Clinical and pathologic factors were recorded along with neoadjuvant chemotherapy and comorbidities. Pathologic outcomes included those with CR (pT0) and near CR (nCR = pT0/Ta/Tis). Odds ratio (OR) for CR and nCR were calculated using multivariate logistic regression adjusting for demographic (age, gender, race), medical (creatinine, diabetes mellitus, cardiac disease) and clinical factors (clinical T stage, prior BCG therapy, complete tumor debulking prior to chemotherapy).nnnRESULTSnA total of 78 patients received GC or MVAC neoadjuvant chemotherapy followed by RC, including 46 who received GC and 32 who received MVAC. There was no difference in gender, renal function, cardiac disease or clinical stage between the two groups. Patients over 70 years of age primarily received GC (17/18). CR was achieved in 30% and 25% (p = 0.15) of GC and MVAC patients, respectively (multivariate OR 0.42, 95% CI 0.11-1.63). nCR was more common in those receiving GC (50% vs. 38%, p = 0.04) although non-significant in the multivariate model (OR 0.30, 95% CI 0.07-1.16).nnnCONCLUSIONSnWe observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of bladder cancer patients. These observations support the use of GC as an alternative regimen in the neoadjuvant setting.

New approaches to bladder-surveillance endoscopy

Bladder cancer is the fifth most common cancer in the United States1 and has a 50% recurrence rate. Consequently, patients undergo frequent surveillance, where a flexible endoscope is inserted into the bladder to detect recurrent tumors. The exam can be uncomfortable, in part because of the large (5mm) devices currently employed. While use of smaller endoscopes is desirable, they suffer from reduced resolution and field of view, making examination and detection challenging. Additionally, bladder surveillance constitutes a significant percentage of urologists’ time and resources, and is costly. While avenues for improved detection of bladder cancer—such as biomarkers,2 fluorescence imaging,3 and narrow-band imaging4—are areas of current investigation, conventional endoscopy remains the gold standard. Limitations of current devices have spurred development of mosaicking systems that generate panoramic views of the bladder. Constructed from multiple overlapping images, mosaics provide expanded views and greater visual context for in situ detection and assessment of mucosal changes associated with carcinoma. However, the resulting panoramas are limited to localized regions of the bladder and are unable to generate full, sweeping 360 views. Here, we report our developments toward automated surveillance that uses novel endoscopic technology and image-analysis software to reconstruct full 3D panoramas of the bladder.5 We developed an ultrathin scanning-fiber endoscope (SFE), whose small diameter (1.5mm) and superior imaging capabilities make it ideal for endoscopic surveillance (see Figure 1).6 In addition to mitigating patient discomfort, we have configured the SFE with an automated tip-bending system that allows machine-controlled surveillance endoscopy.7, 8 By employing a spiral scan trajectory, we can image the entire internal surface (see Figure 2). This operationally simple system could potentially be performed by a nurse or technician, thus freeing up the urologist’s time. In conjunction with these hardware Figure 1. Scanning-fiber endoscope image probe.

MP86-16 A MULTI-CENTER ANALYSIS OF PROSTATE CANCER (PCA) TREATMENT AMONG VETERANS FOLLOWING INTRODUCTION OF THE 17-GENE GENOMIC PROSTATE SCORE (GPS) ASSAY

RESULTS: 627 men were eligible for the study. Age, ethnicity, primary language, education and Charlson comorbidity did not differ across PSA strata. Compared to the referent group PSA <10, those with PSA 50 were more likely to receive androgen deprivation therapy as their primary form of treatment (p <0.01). Patients with PSAs 10-19.9 were more likely to have sexual bother (b1⁄411.1, p<0.03) compared to the referent group. (See Table) There were no other differences in other HRQOL domains across PSA strata. CONCLUSIONS: In this population, we found no statistically significant difference in HRQOL outcomes by PSA level. The finding that patients with very elevated PSA levels having outcomes that were no worse than patients with less aggressive disease is important clinically because most quality of life detriments tend to be from treatment of localized disease. Further, these findings will inform physicians on patient symptomatology despite PSA level.

Prevalence and adverse impact of extended antibiotic prophylaxis in urologic oncology surgery.

294 Background: Providers exhibit variation in the selection of the class, dose, and duration of prescribed antibiotic prophylaxis (ABP) to prevent postsurgical infections. We sought to evaluate ABP practice patterns for common inpatient urologic oncology surgeries and ascertain the association between extended ABP and hospital-acquired Clostridium difficile (C. diff) infections. Methods: From the PREMIER database for 2007–2012, we identified patients who underwent radical prostatectomy (RP), radical or partial nephrectomy (Nephx), or radical cystectomy (RC). We defined extended ABP from charges for antibiotics ≥ 2 days after surgery; exclusive of patients with a switch in antibiotic class within 2 postoperative days for presumption of infection. We identified postoperative C. diff infections using ICD-9 diagnosis codes. Hierarchical linear regression models were constructed by procedure to identify patient and provider factors associated with extended ABP. Logistic regression models evaluated the associa...

1901 INCREASED RISK OF MORTALITY FROM SQUAMOUS CELL CARCINOMA OF THE BLADDER AMONG WOMEN IN THE UNITED STATES

INTRODUCTION AND OBJECTIVES: Squamous cell carcinoma of the bladder (SCC) is distinct from urothelial carcinoma of the bladder (UC) in epidemiology, risk factors, appearance, and clinical course. Prior studies have suggested that women with UC have worse disease-specific survival (DSS) than men, but this has not been thoroughly studied in SCC. The incidence of SCC among is more similar among men and women that with UC. We compared DSS of men and women with SCC using a large, population-based cancer database and examined the effect of tumor stage and treatment type on the difference between these groups. METHODS: We identified incident SCC cases from the Surveillance, Epidemiology, and End Result (SEER) national cancer registry. Cox proportional hazard models were used to identify differences in survival between men and women. Analyses were adjusted for age, race, year of diagnosis, and tumor characteristics (stage, grade, and the presence of lymphatic and distant metastases.) Stratified analyses were also performed for localized tumors based on treatment received and tumor stage. RESULTS: A total of 2,523 cases of SCC were identified, 1,248 women and 1,275 men. At diagnosis, women were older than men (mean age 72.8 /13.0 years v. 71.0 /12.7 years, respectively, p 0.001). When adjusted for demographic and tumor characteristics, women had a 20% increased risk of mortality from SCC than men (HR 1.2, 95% CI 1.1-1.4, p 0.002). A similar difference was seen when the analysis was restricted to just those who received cystectomy (HR 1.2, 95% CI 1.1-1.4). However, a survival difference was not seen between men and women with positive lymph nodes or distant metastases (HR 1.1, 95% CI 0.9-1.4, p 0.345). When stratified by tumor stage, those with non-muscle invasive disease (Ta, Tis, and T1), where women were at 2.3-fold higher risk of death (HR 2.3, 95% CI 1.4-4.0, p 0.002). Women with muscle invasive disease (T2) and disease extending outside the serosa of the bladder (T3 and T4) tended to have a higher risk of mortality, although this difference was not significant (HR 1.1, 95% CI 0.9-1.4, p 0.373 and HR 1.1, 95% CI 0.9-1.4, p 0.310). CONCLUSIONS: Women with clinically localized SCC appear to have worse DSS than men. This is not true among those with lymph node positive or metastatic disease. The difference in DSS among women with local disease was most prominent among those with non-muscle invasive cancer. Taken together, these differences in DSS between men and women with localized SCC of the bladder suggest that the nature of the tumor, delivery of therapy, or response to therapy differs by gender.