Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PURPOSE: We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. MATERIALS AND METHODS: NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. RESULTS: Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). CONCLUSIONS: Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors.

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PURPOSE: Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). METHODS: We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. RESULTS: One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. CONCLUSION: Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Early discharge after laparoscopic or robotic partial nephrectomy: care pathway evaluation.

OBJECTIVE: To determine the success of our clinical care pathway for laparoscopic (LPN) and robotic partial nephrectomy (RPN) and to examine factors predictive for success. PATIENTS AND METHODS: A retrospective review of our Institutional Review Board-approved prospectively maintained minimally invasive PN database yielded 263 consecutive minimally invasive PNs from 2003 to 2010. Patient, disease and surgery-related factors were collected. The primary endpoint was successful implementation of the clinical pathway with discharge on postoperative day (POD 1). Associated factors were modelled using univariate and multivariable logistic regression to determine factors predictive for success of the pathway. RESULTS: Overall, 157 (60%) of the patients had successful care pathway implementation with POD1 discharge, of which 46 (17%) were RPNs. The overall readmission rate was 5% (12/263) and similar for patients discharged on POD 1, 4.5% (7/157). Several patient-related, tumour-related, and surgical factors were associated with care pathway success. In a multiple logistic regression model, only surgery period (late cohort vs early cohort) was significant for successful pathway implementation (odds ratio 4.2; 95% confidence interval 2.1-8.4, P < 0.001). CONCLUSIONS: Early discharge care pathways can be successfully implemented for LPN or RPN with low readmission rates. Care pathway success improves with institutional experience.

Does robot-assisted laparoscopic ileocystoplasty (RALI) reduce peritoneal adhesions compared with open surgery?

OBJECTIVES: To compare perioperative outcomes between open ileocystoplasty and robot-assisted laparoscopic ileocystoplasty (RALI) in a porcine model, as objective data comparing outcomes between these two approaches in children with neurogenic bladder are lacking. We specifically examined differences in postoperative peritoneal adhesion formation between the groups. MATERIALS AND METHODS: In all, 20 pigs were assigned to an open ileocystoplasty or RALI study arm. All the pigs underwent an initial urodynamic study (UDS). In the RALI arm, reconstructive steps were performed intracorporeally using a standard da Vinci(®) system. Postoperatively, variables including first stool, weight gain, and complications were recorded. After 42 days, the pigs underwent a final UDS followed by adhesion assessment. Intraperitoneal adhesions were quantified by a third-party 'blinded' surgeon according to previously described objective scoring systems. RESULTS: Preoperative variables including UDS were similar in both groups. Overall operating time was significantly shorter for open ileocystoplasty than for RALI (149 vs 287 min, P < 0.001, respectively). Postoperatively, all variables including time to first stool, weight gain, and urodynamic parameters were similar amongst the groups. Pigs in the open arm developed significantly more adhesions (P = 0.02) and adhesions with a higher complexity (P = 0.04). CONCLUSIONS: In this porcine model, RALI achieved similar functional outcomes as the open approach, but required longer procedural times. The number and complexity of surgical adhesions among the groups favoured the RALI cohort. This may be of clinical significance in the paediatric spina bifida population, who generally undergo multiple surgical procedures in their lifetime, with increased risk for development of adhesions and subsequent intestinal obstruction.

Hepatic PSMA-Avid Postradiation Inflammation.

ABSTRACT: A 62-year-old man with de novo large volume metastatic prostate cancer to the bone, liver, and nodes status post multiple lines of therapy including external beam radiation to T12-L2 approximately 13 months prior underwent 68 Ga-PSMA PET/CT to determine eligibility for 177 Lu-PSMA therapy. 68 Ga-PSMA PET/CT demonstrated tracer-avid osseous and nodal lesions consistent with metastases. In addition, regional geographic tracer avidity was seen in the midline left hepatic lobe associated with capsular retraction and demonstrated no FDG avidity on subsequent imaging, probably inflammatory related to prior radiation to T12-L2.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.

BACKGROUND: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. CONCLUSIONS: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.

Short (≤ 1 mm) positive surgical margin and risk of biochemical recurrence after radical prostatectomy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: It has been suggested that a very short positive margin does not confer additional risk of BCR after radical prostatectomy. This study shows that even very short PSM is associated with increased risk of BCR. OBJECTIVE: To re-evaluate, in a larger cohort with longer follow-up, our previously reported finding that a positive surgical margin (PSM) ≤ 1 mm may not confer an additional risk for biochemical recurrence (BCR) compared with a negative surgical margin (NSM). PATIENTS AND METHODS: Margin status and length were evaluated in 2866 men treated with radical prostatectomy (RP) for clinically localized prostate cancer at our institution from 1994 to 2009. We compared the BCR-free survival probability of men with NSMs, a PSM ≤ 1 mm, and a PSM < 1 mm using the Kaplan-Meier method and a Cox regression model adjusted for preoperative prostate-specific antigen (PSA) level, age, pathological stage and pathological Gleason score (GS). RESULTS: Compared with a NSM, a PSM ≤ 1 mm was associated with 17% lower 3-year BCR-free survival for men with pT3 and GS ≥ 7 tumours and a 6% lower 3-year BCR-free survival for men with pT2 and GS ≤ 6 tumours (log-rank P < 0.001 for all). In the multivariate model, a PSM ≤ 1 mm was associated with a probability of BCR twice as high as that for a NSM (hazard ratio [HR] 2.2), as were a higher PSA level (HR 1.04), higher pathological stage (HR 2.7) and higher pathological GS (HR 3.7 [all P < 0.001]). CONCLUSION: In men with non-organ-confined or high grade prostate cancer, a PSM ≤ 1 mm has a significant adverse impact on BCR rates.

Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers.

BACKGROUND: Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer. METHODS: Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression. RESULTS: SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034). CONCLUSIONS: SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance.

Correlation of 68Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study.

Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance and promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pancancer theranostic agents. This study aimed to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether 68Ga FAP inhibitor (FAPi)-46 PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening using immunohistochemistry on a pancancer human tissue microarray (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent 1 whole-body 68Ga-FAPi-46 PET/CT scan and, subsequently, surgical resection of their primary tumor or metastasis. 68Ga-FAPi-46 PET SUVmax and SUVmean was correlated with FAP immunohistochemistry score in cancer and tumor-adjacent non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancer types on tissue microarray with variable intensity and frequency, ranging from 25% to 100% (mean, 76.6% ± 25.3%). Strong FAP expression was observed in 50%-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary, and pancreas. Fifteen patients with various cancer types (colorectal [n = 4], head and neck [n = 3], pancreas [n = 2], breast [n = 2], stomach [n = 1], esophagus [n = 2], and uterus [n = 1]) underwent surgery after their 68Ga-FAPi-46 PET/CT scan within a mean interval of 16.1 ± 14.4 d. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in tumor-adjacent non-cancer tissue: mean SUVmax 7.7 versus 1.6 (P < 0.001), mean SUVmean 6.2 versus 1.0 (P < 0.001), and mean FAP immunohistochemistry score 2.8 versus 0.9 (P < 0.001). FAP immunohistochemistry scores strongly correlated with 68Ga-FAPi 46 SUVmax and SUVmean: r = 0.781 (95% CI, 0.376-0.936; P < 0.001) and r = 0.783 (95% CI, 0.379-0.936; P < 0.001), respectively. Conclusion: In this interim analysis of a prospective exploratory imaging trial, 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlated with FAP tissue expression. These findings support further exploration of FAPi PET as a pancancer imaging biomarker for FAP expression and as a stratification tool for FAP-targeted therapies.

Robotic radical prostatectomy for elderly patients: probability of achieving continence and potency 1 year after surgery.

PURPOSE: We assessed the probability of achieving continence and potency after robotic radical prostatectomy in elderly patients. MATERIALS AND METHODS: The cohort included 1,436 robotic radical prostatectomy cases performed at our institution between 2003 and 2008. Continence (pad-free) and potency (erection sufficient for intercourse) at baseline and 1 year after surgery were evaluated by the UCLA-PCI questionnaire. Point estimates of the predicted probabilities of continence and potency for age 65, 70 and 75 years were calculated from multivariate logistic regression models adjusting for age, nerve sparing status, baseline International Prostate Symptom Score and baseline Sexual Health Inventory for Men score. Patients who were impotent before surgery or those who received hormones or radiation within 1 year after surgery were censored. RESULTS: Mean patient age was 60 years (range 38 to 85) with 25% older than 65 years and 77 (5%) 70 years old or older. Age (OR 0.97, p = 0.002), baseline I-PSS (OR 0.98, p = 0.02) and Sexual Health Inventory for Men scores (OR 1.02, p = 0.005) were independently associated with being pad-free. Age (OR 0.92, p <0.0001), baseline Sexual Health Inventory for Men score (OR 1.1, p <0.0001) and bilateral nerve sparing (OR 2.92, p <0.0001) were independently associated with achieving potency. Predicted probabilities (95% CI) of postoperative 1-year continence at age 65, 70 and 75 years were 0.66 (0.63, 0.69), 0.63 (0.57, 0.68) and 0.59 (0.52, 0.66), respectively. The corresponding probabilities of postoperative 1-year potency after bilateral nerve sparing were 0.66 (0.62, 0.71), 0.56 (0.49, 0.64) and 0.46 (0.36, 0.56). CONCLUSIONS: In our experience there is an acceptable probability of achieving continence and potency after robotic radical prostatectomy in selected elderly patients.