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Purpose: Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance, promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pan-cancer theranostic agents. This study aims to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether gallium-68 FAPi-46 (68Ga-FAPi-46) PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening by using immunohistochemistry on a pan-cancer human tissue microarray (TMA) (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent one whole body 68Ga-FAPi-46 PET/CT scan and subsequently, surgical resection of their primary tumor and/or metastasis. 68Ga-FAPi-46 PET maximum standardized uptake value (SUVmax and SUVmean) was correlated with FAP immunohistochemistry score in cancer and non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancers types on TMA 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 following their 68Ga-FAPi-46 PET/CT scan within a mean time interval of 16.1±14.4 days. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in normal tissue: mean SUVmax 7.7 vs 1.6 (p

In this article, we provide an overview of established and emerging conventional nuclear medicine and PET imaging biomarkers, as the diagnostic nuclear medicine portfolio is rapidly expanding. Next, we review briefly nuclear theranostic approaches that have already entered or are about to enter clinical routine. Using some approximations and taking into account emerging applications, we also provide some simplified business forecasts for nuclear theranostics. We argue that an optimistic outlook by the nuclear medicine community is crucial to the growth of the specialty and emphasize the urgent need for training adaptations.

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

Context: Fibroblast activation protein (FAP)-expressing cancer associated fibroblasts (CAFs), a major component of tumor stroma, confer treatment resistance, promote local progression, metastasis and immunosuppression. Because FAP is selectively expressed in the tumor stroma of many cancers, radiolabeled small molecule ligands targeting FAP are being explored for their use as pan-cancer theranostic agents. As a required step for further translation and approval by regulatory agencies FAPi PET imaging must be show to be a reliable biomarker of FAP expression in cancer and non-cancer tissues. The aim of the study is to define the incidence and degree of FAP expression by immunohistochemistry (IHC) across various cancers using Tissue Microarrays (TMAs) and to explore whether gallium-68 FAPi-46 PET image biodistribution faithfully reflects tumor FAP expression from resected tumor and non-tumor specimens. Methods: This was a prospective, exploratory, open-label, single-center imaging trial in cancer patients conducted in 2020. Patients scheduled to undergo surgical resection of the primary tumor and/or metastases were eligible. Patients underwent one whole body 68Ga-FAPI-46 PET/CT scan and subsequently underwent surgical resection of the primary tumor and/or metastasis. The primary endpoint measure was the Correlation of 68Ga-FAPI-46 PET maximum standardized uptake value (SUVmax) with FAP IHC score in cancer and non-cancer tissue. Results: The incidence of FAP expression in TMAs from 14 cancers ranged from 25 to 100% (mean 76.6± 25.3). 15 patients with the following cancer types were included: colorectal (n=4), head and neck (n=3), pancreas (n=2), breast (n=2), stomach (n=1), esophagus (n=2) and uterus (n=1). All 15 patients subsequently underwent surgery after the scan with a mean time interval of16.1 ± 14.4 days (range 1 - 50 days). Tumor resection was not attempted in 2 patients because unresectable. FAPI SUVmax and IHC score were higher in cancer tissue than in normal tissue: mean FAPI SUVmax 7.4±4.6 (range 1.5-15.9) vs 1.6±1.2 (range 0.4-5.1), (p Citation Format: Christine E. Mona, Matthias Benz, Firat Hikmat, Tristan G. Grogan, Katharina Lueckerath, Aria A. Razmaria, Rana Riahi, Roger Slavik, Mark D. Grigis, Giuseppe Carlucci, Kimberly A. Kelly, Johannes Czernin, David W. Dawson, Jeremie Calais. Validation of FAPi PET biodistribution by immunohistochemistry in patients with solid cancers: a prospective exploratory study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB038.

Background A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. Objective To assess pathologic stage of pure GS6 at radical prostatectomy (RP). Design, setting, and participants In the period 2003–2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a–b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. Outcome measurements and statistical analysis Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. Results and limitations Of the 60 GS6 pT3a–b cases identified in the period 2003–2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. Conclusions In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. Patient summary GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

Background and Objectives: Loss of erectile function is common after prostatectomy, and surgeons have long sought techniques that reduce this adverse outcome. This study was conducted to assess erectile function after robot-assisted laparoscopic prostatectomy, with and without hydrodissection (HD) of the neurovascular bundles (NVBs). Methods: Using a database of 335 consecutive RALP procedures conducted by 2 surgeons, we identified all nerve-sparing surgeries performed by HD or standard dissection (SD). The primary and secondary endpoints were Sexual Health Inventory for Men (SHIM) scores and surgical margin positivity, respectively. Subset analyses were performed on men with preoperative SHIM scores ≥17. Determinants of the postoperative SHIM score were evaluated by multivariate linear regression. Results: Among men with preoperative SHIM scores ≥17 who underwent bilateral complete nerve sparing (n = 73), mean preoperative SHIM scores were similar in the HD and SD groups, but were significantly higher in the HD group at 6 months (16.1 ± 8.6 vs 8.3 ± 8.1; P = .024) and >1 year after surgery (16.9 ± 7.1 vs 9.1 ± 6.4; P = .004). According to multivariate linear regression analysis including all patients, HD at RALP (odds ratio [OR] 6.9; 95% confidence interval (CI) 2.8–11.0; P = .001) and preoperative SHIM score were independent predictors of erectile function at >1 year after surgery. There was no significant difference in surgical margin positivity between groups (P = .36). Conclusion: HD of the NVB appears to improve erectile function after RALP.

Although the natural history of urothelial carcinoma of the bladder (UCB) from radical cystectomy (RC) to disease recurrence (DR) has been investigated intensively, the course of patients who have experienced DR after RC for UCB remains poorly understood.To evaluate the prognostic value of the Bajorin criteria that consists of two risk factors: Karnofsky performance status (KPS) and the presence of visceral metastases (VMs) in patients with DR after RC for UCB. Furthermore, to identify additional factors associated with cancer-specific mortality (CSM) and thus build a multivariable model to predict survival after DR.We identified 967 patients with UCB who underwent RC at 17 centers between 1979 and 2012 and experienced DR. Of these, 372 patients had complete data we used for analysis.Univariable Cox regressions analysis was performed. We used a forward stepwise selection process for our final multivariable model.Within a median follow-up of 18 mo, 266 patients died of disease. Cancer-specific survival at 1 yr was 79%, 76%, and 47% for patients with no (n=105), one (n=180), and two (n=87) risk factors (p0.001; c-index: 0.604). On multivariable analyses, we found that KPS80%, higher American Society of Anesthesiologists score, anemia, leukocytosis, and shorter time to DR (all p values0.034) were independently associated with increased CSM. The combination of time to DR and KPS resulted in improved discrimination (c-index: 0.694).We confirmed the prognostic value of KPS and VMs in patients with DR following RC for UCB. We also found several other clinical variables to be associated with worse CSM. We developed a model for predicting survival after DR inclusive of time to DR and KPS assessed at DR. If validated, this model could help clinical trial design.We developed a model to predict survival following disease recurrence after radical cystectomy for urothelial carcinoma of the bladder, based on time to disease recurrence and Karnofsky performance status.

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). 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. 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. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason

OBJECTIVES: Evaluation of the precision of prostate tissue ablation with MRI guided therapeuticultrasound by intraoperative objective assessment of the neurovascular bundle in canines in-vivo. METHODS: In this ongoing IACUC approved study, eight male canines were scanned in a clinical 3T Achieva MRI scanner (Philips) before, during, and after ultrasound therapy with a prototype MR-guided ultrasound therapy system (Philips). The system includes a therapy console to plan treatment, to calculate real-time temperature maps, and to control ultrasound exposures with temperature feedback. Atransurethral ultrasound applicator with eight transducer elements was used to ablate canine prostate tissue in-vivo. Ablated prostate tissue volumes were compared to the prescribed target volumes to evaluate technical effectiveness. The ablated volumes determined by MRI (T1, T2, diffusion, dynamic contrast enhanced and 240 CEM43 thermal dose maps) were compared to H&E stained histological slides afterprostatectomy. Potential ...

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.

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.

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

Purpose Urinary retention is a known complication of using an extravesical approach for ureteral reimplantation, especially in bilateral cases. The etiology may be secondary damage to pelvic nerves during ureteral dissection. Recent literature suggests that it is possible to visually identify these nerves during a robotic assisted laparoscopic approach. We performed an exploratory study to identify and document them in pediatric patients by means of electrophysiologic recordings. Material and methods Seven consecutive patients undergoing robotic assisted laparoscopic ureteral reimplantation with extravesical approach were prospectively enrolled in the study. Following dissection of the ureter below the level of vas deferens in male and the uterine artery in female, staying close to the adventitia and approaching the ureterovesical junction, the fibers as described in human cadaveric studies were identified dorsomedial to the ureter and preserved. Stimulating and recording electrodes were passed through to record post-synaptic compound muscle action potentials of the bladder. Results Even though the nerve fibers were visually identified, we were unable to consistently and reproducibly record compound muscle action potentials after stimulation of putative pelvic plexus fibers at the distal ureter, despite modulation in stimulation intensity, pulse characteristics, signal recording sensitivity and stimulator probe variation. Conclusions In this pilot study, the inconsistent findings raise questions about the exact location of the neurovascular bundle, nature of bladder smooth muscle electrophysiology and the appropriate methodology of evaluation. This may provide a reason to reexamine the intraoperatively expected location of pelvic plexus nerve fibers.

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.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.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, p0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647).Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

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.

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. Prostate 72:157–164, 2012. © 2011 Wiley Periodicals, Inc.

OBJECTIVE To evaluate the impact of prostate weight (PW) on probability of positive surgical margin (PSM) in patients undergoing robotic-assisted radical prostatectomy (RARP) for low-risk prostate cancer. METHODS The cohort consisted of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific antigen

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.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.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 (p0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05).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.

Several institutional studies have suggested that pathological Gleason score≤6 prostate cancer has little or no capacity for metastasis.Using the Surveillance, Epidemiology, and End Results database (SEER, 2004-2011, n = 19,594) and the National Cancer Database (NCDB, 2004-2013, n = 57,540), we identified patients with pathological Gleason score≤6 prostate cancer following radical prostatectomy and lymph node dissection. At the University of Chicago Medicine (UCM, 2003-2014), we considered men with Gleason score≤6 prostate cancer who did (n = 267) and did not receive (n = 770) a lymph node dissection at the time of radical prostatectomy. Temporal trends in lymph node dissection and lymph node metastases were determined, and multivariable logistic regressions were used to analyze factors associated with lymph node metastases. In the UCM cohort, we also evaluated secondary endpoints, including biochemical recurrence (BCR), metastatic disease on follow-up imaging, and response to salvage radiation therapy.The incidence of lymph node dissection at the time of radical prostatectomy decreased from 60% to 37% in SEER (2004-2011) and from 62% to 45% in NCDB (2004-2013). Positive lymph node metastases were found in 0.2% of SEER and 0.18% of NCDB patients who received a lymph node dissection. Elevated PSA, higher clinical stage, and African American race were associated with lymph node positivity in one or both of these databases (P0.05). Among UCM patients who received a lymph node dissection, no lymph node metastases were found, though a BCR occurred in 3 cases (1%). All 3 men responded favorably to salvage therapy, suggestive of local recurrence. A total of 21 patients (3%) from UCM who did not receive a lymph node dissection had a BCR and underwent salvage radiation therapy. Of these, 4 patients had persistently detectable PSA levels without evidence of local or distant disease at median follow-up of 65 months (range: 29-79) following salvage therapy. Surgical specimens were available for contemporary pathologic review in 3 of these cases, and all were upgraded to Gleason 7 disease.Our population-based and institutional analyses suggest metastases in cases of Gleason score≤6 prostate cancer to be extremely rare.

To determine the success of our clinical care pathway for laparoscopic (LPN) and robotic partial nephrectomy (RPN) and to examine factors predictive for success.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.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, P0.001).Early discharge care pathways can be successfully implemented for LPN or RPN with low readmission rates. Care pathway success improves with institutional experience.

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.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).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 PSM1 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).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 P0.001 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 P0.001]).In men with non-organ-confined or high grade prostate cancer, a PSM ≤ 1 mm has a significant adverse impact on BCR rates.

Previous studies have demonstrated differences in surgical outcomes after radical prostatectomy based on ethnicity. We compared sexual and urinary outcomes in African-American (AA) patients 6 and 12 months after robot-assisted radical prostatectomy (RARP) with those of non-AA patients.We reviewed our RARP database at our institution for patients with at least 12 months of follow-up. Erectile function was defined using the University of California, Los Angeles Prostate Cancer Index as erections "firm enough for masturbation and foreplay" or "firm enough for intercourse," while urinary continence was defined as being "pad free." Only patients who were potent and pad free preoperatively were included in the analysis. Multivariate logistic regression was used to compare postoperative potency and urinary pad-free status between AA and non-AA patients while controlling for pertinent demographic, clinical, and pathologic variables.In the urinary continence analysis, 140 AA patients and 576 non-AA patients were included, compared with 105 AAs and 500 non-AA patients who were included in the analysis of sexual function. At 12 months postoperatively, a smaller proportion of AA patients were potent compared with non-AA patients (60% vs 76.4%, P=0.001). Similarly, we found a lower incidence of pad-free status for AA patients at 12 months postoperatively (55.7% vs 69.8%, P=0.039). Similar functional results were found at 6 months postoperatively for both analysis groups.AA men appear to have worse urinary and sexual outcomes at 12 months after RARP compared with non-AA patients. At 6 months, there is no statistically significant difference. Further, longer-term studies are needed to validate these results.

Clinical and surgical factors predict renal function decline after laparoscopic partial nephrectomy (LPN). Additional histopathologic predictors may be found in the specimen's nonneoplastic tissue but were not studied. This study investigated the significance of histologic findings in addition to other known predictors of renal function after LPN.Data of 150 patients who underwent LPN was analyzed. Renal function changes (median follow-up 15 months) were correlated with perioperative and histopathologic parameters. Three histopathologic features were evaluated and graded in the nonneoplastic parenchyma: Glomerulosclerosis, arteriosclerosis (AS), and interstitial fibrosis/tubular atrophy. Estimated GFR (eGFR) and percent decline on postoperative day 1 (POD1) and at the last follow-up were measured.Median eGFR percent decline at POD1 and last follow-up was -17 and -10, respectively (P0.001). New-onset ≥stage III chronic kidney disease developed in only 7% of the patients. Three factors independently predicted POD1 eGFR decline: Artery and vein clamping vs artery only clamping (P=0.002), male sex (P=0.015), and larger tumor (P=0.02). Long-term loss of renal function was associated with POD1 eGFR decline (P=0.002) and the percentage of AS (P=0.01). The study limitations include a retrospective analysis leading to variability in the follow-up length and a small size cohort.LPN is associated with a favorable renal function outcome in most patients. Pathologic findings in the nonneoplastic tissue, in addition to clinical parameters, can be used to predict which patients are more likely to experience renal function impairment.

Infection or malfunction of ventriculo-peritoneal (VP) shunts is a severe complication during laparoscopic surgery involving the gastrointestinal or urinary tract. It has been recently suggested to externalize the shunt or convert into a ventriculo-atrial shunt to prevent this complication with laparoscopic approach. Herein, we present a novel technique for management of the VP shunt during robot-assisted laparoscopic (RAL) urologic procedures.After port placement and diagnostic peritoneoscopy, an Endopouch bag (Ethicon Endo-Surgery) was inserted into the peritoneal cavity and the distal end of the shunt was placed into the pouch. The Endopouch suture was synched around the shunt and the pouch was placed in the subhepatic space during the surgery. The intraperitoneal pressure was maintained at 12 mm Hg during the entire procedure. Metronidazole, gentamicin, and vancomycin were administered as prophylaxis. Following the completion of the surgery and profuse irrigation of the peritoneal cavity, the shunt was repositioned within the peritoneum. We evaluated perioperative shunt-related complications.We used this technique in four patients with VP shunt undergoing RAL cystoplasty and appendicovesicostomy and/or colonic enema channel formation. The average age of the patient at surgery was 10.8 (7-14) years. One patient was converted to open because of failure to progress due to multiple adhesions and the shunt was externalized temporarily. At a mean follow-up of 13 (3-20) months, no shunt-related complications were seen.In our preliminary experience, the use of an intracorporeal Endopouch bag with controlled pneumoperitoneal pressure to protect the VP shunt may be an effective alternative to prevent complications related to it during RAL urologic surgery involving the gastrointestinal or urinary tract. Further studies will be needed to confirm our results.

The Rotablator is an angioplasty device that is passed over a wire. It uses a high-speed rotational "burr" (2 mm in diameter) that is coated with microscopic diamond particles and cooled by saline. It rotates at high speed (approximately 200,000 rpm) breaking up endovascular blockage into minute (smaller than red blood cells) fragments. We investigated, in vitro and ex vivo, the possible use of the Rotablator for urinary stone disease.Human stones of different sizes and composition were used for the experiment. Stone impaction in vitro was modeled by wedging the stones into the proximal part of a 16F silicone Foley catheter. Likewise, an ex-vivo study was performed on stones placed into a freshly harvested swine ureter using a nitinol basket. Data regarding the drill time, remaining stone size, and ureteral damage were collected.Overall, 15 stones were treated (10 in vitro and 5 ex vivo). The device successfully drilled through all the stones, along the path of the guidewire, allowing complete passage of the burr. The pretreatment mean stone size for the silicone and ureteral testing was 65 mm(3) and 34 mm(3), respectively (both P0.01). The post-treatment size was 54 mm(3) and 24 mm(3), respectively. Average treatment time was 100 seconds. No visual macroscopic ureteral damage or perforation was observed.In vitro, the Rotablator is capable of drilling through stones with minimal damage. Drilling, however, occurred alongside the stone in which the guidewire was located and, thus, stone fragmentation appears to be minimal. Further studies are necessary to investigate other burr configurations and the use of the Rotablator for the fluoroscopic-guided passage of ureteral impaction in difficult clinical settings.

We assessed the probability of achieving continence and potency after robotic radical prostatectomy in elderly patients.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.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, p0.0001), baseline Sexual Health Inventory for Men score (OR 1.1, p0.0001) and bilateral nerve sparing (OR 2.92, p0.0001) 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).In our experience there is an acceptable probability of achieving continence and potency after robotic radical prostatectomy in selected elderly patients.

Several robot-assisted radical prostatectomy (RARP) series have reviewed the impact of the initial learning curve on perioperative outcomes. However, little is known about the impact of experience on urinary and sexual outcomes. Herein, we review the perioperative, pathological and functional outcomes of our initial 700 consecutive procedures with at least 1 year follow up.From 2003-2006, 700 consecutive men underwent RARP at a single, academic institution. Perioperative data and pathologic outcomes were prospectively collected. Validated, UCLA-PCI-SF36v2 quality-of-life questionnaires were also obtained at 1, 3, 6 and 12 months following surgery. Outcomes between groups (cases 1-300, 301-500, and 501-700) were compared.Mean operative time (OT) and blood loss significantly decreased during the experience (286, 198, 190 min; por= 0.001; 266, 190, 169 ml; por=0.001). Positive surgical margin (PSM) rate decreased in pT2 patients (15% versus 10% versus 7%; p = 0.03) despite operating on men with higher grade disease (biopsy GSor=7 in 24%, 40%, 44%; por= 0.001). At 12 months postRARP, pad free continence rate was 81% when self reported and 62% when assessed by the UCLA-PCI-SF36v2 questionnaire in the initial group. Continence rates improved to 93% and 75%, respectively, for cases 501-700 (por= 0.05). Furthermore, significant improvement in continence rates between consecutive case groups was observed at all postoperative time points. Potency rate was 83% (bilateral nerve preservation) and 56% (unilateral nerve preservation) at 12 months when self reported and 63% and 37% respectively by the UCLA-PCI-SF36v2. No significant differences in sexual function were noted with increased experience.A prolonged learning curve is observed for EBL, OT and pT2-PSM. In addition, to the best of our knowledge, this is first series demonstrating a continued improvement in urinary continence with increased RARP experience.

The potential of a new continuous-wave (CW) 70-W, 2.013-microm thulium-doped yttrium aluminium garnet (Tm:YAG) laser for the endoscopic treatment of benign prostatic hyperplasia (BPH) is investigated.The simultaneous combination of vaporisation and resection of prostatic tissue in a retrograde fashion is the main characteristic of this new laser technique. We provide a DVD that shows the main steps of this procedure.We retrospectively evaluated 56 nonconsecutive patients who were treated by thulium laser vaporesection of the prostate in our institution between 2005 and 2007.Vaporesection of the prostate is performed by moving the fibre semicircumferentially from the verumontanum towards the bladder neck, thereby undermining tissue and cutting chips.Blood loss, postvoiding residual urine (PVRU), maximum flow rate (Q(max)), and the International Prostate Symptom Score (IPSS) were measured as well as prostate volume and prostate-specific antigen (PSA). The duration of the procedure, need for postoperative irrigation, duration of catheterisation, and hospital stay were recorded.The median procedure time was 60 min, postoperative irrigation was necessary in 19 out of 56 patients, and the median duration of catheterisation was 23 hr. At the day of discharge, the mean haemoglobin value decreased by 0.2mg/dl (p=0.13), the average Q(max) improved from 8.1 to 19.3 ml/s (p0.001), and the PVRU decreased from 152 ml to 57 ml (p0.05). The blood transfusion rate was 3.6%, and two patients needed a recatheterisation postoperatively (3.6%). After a median follow-up of 9 mo, the IPSS improved from 19.8 at baseline to 8.6 (p0.001). Four patients had a repeat transurethral resection of the prostate (TURP) during the learning curve, but this was not necessary in any of the later patients. One patient developed a urethral stricture, and another developed a bladder neck contracture.The thulium laser seems to be a suitable tool for the endoscopic treatment of BPH.

e16084 Background: The robotic surgery has been extensively adopted in many surgical areas, especially in Urology. It's proven benefits (less blood loss, shorter recovery and reduced complication rates) has made it the most popular method to perform a radical prostatectomy nowadays. However, scarce data exists on the long-term oncologic outcome of robotic assisted laparoscopic prostatectomy (RALP). Since 2003, over 3,000 RALPs have been performed at our institution. We report the midterm oncologic outcome data of 1,054 patients with a median follow up of 60 months after RALP. Methods: From March 2003 to August 2008, 1,054 patients underwent RALP. Prospectively attained clinical data has been stored in an IRB approved database. Follow up has been maintained every 6 months for 2 years, and yearly thereafter. Salvage RALPs were excluded. Biochemical recurrence (BCR) defined as PSA > 0.2ng/ml, disease free survival, cancer specific and overall survival were assessed. Results: Of the 1,054 patients within the database, 1,019 met the criteria for evaluation. Mean age was 60 years (IQR 55-65), and mean BMI 27 kg/m2 (IQR 25-30). 181 patiemts (17.3%) were African Americans. Pre-operative mean PSA was 5.3 ng/ml (IQR 4.2-7.4). The majority of patient's clinical stage was T1c [ 776 (73.6%)] while 278 were T2. Biopsy Gleason score (GS) was 6, 7, and ≥8, in 666 (63.2%), 324 (30.7%), and 64 patients (6.1%), respectively. 298 patients underwent a bilateral pelvic lymph node dissection (28.3%). Pathologic GS was 6, 7 and ≥8, in 563 (53.5%), 431 (41%), and 58 patients (5.5%), respectively. The pathological tumor stage was T2 in 834 (79.3%), T3a in 164 (15.6%) and T3b in 54 (5.1%). 14 patients (1.3%) had nodal involvement. Positive surgical margins occurred in 205 cases (20%). BCR occurred in 123 patients (12%). 2 deaths due to prostate cancer (0.2%) and 7 due to other causes (0.7%). Cancer specific survival is thus 99.1% at the mean follow up (60months) by Kaplan Meier analysis. Conclusions: Our midterm oncologic outcomes are consistent with those previously reported in open radical prostatectomy series. Ongoing, long term follow up is necessary in order to solidify it's role in prostate cancer managment.

Purpose For patients who elect to have prostate cancer screening, the optimal time to discontinue screening is unknown. Our objective was to describe rates and predictors of prostate-specific antigen (PSA) screening among older men in the United States. Methods Data were extracted from the population-based 2000 and 2005 National Health Interview Survey (NHIS). PSA screening was defined as a PSA test as part of a routine exam within the past year. Demographic, socioeconomic, and functional characteristics were collected, and a validated 5-year estimated life expectancy was calculated. Age-specific rates of PSA screening were determined, and sampling weight-adjusted multivariate regressions were fitted to determine predictors of screening among men age 70 years or older. Results The PSA screening rate was 24.0% in men age 50 to 54 years, and it increased steadily with age until a peak of 45.5% among age 70 to 74 years. Screening rates then gradually declined by age, and 24.6% of men age 85 years or older reported being screened. Among men age 70 years or older, screening rates varied by estimated 5-year life expectancy: rates were 47.3% in men with high life expectancies (≤ 15% probability of 5-year mortality), 39.2% in men with intermediate life expectancies (16% to 48% probability), and 30.7% in men with low life expectancies (> 48% probability; P < .001). In multivariate analysis, estimated life expectancy and age remained independently associated with PSA screening (P < .001 for each). Conclusion Rates of PSA screening in the United States are associated with age and estimated life expectancy, but excessive PSA screening in elderly men with limited life expectancies remains a significant problem. The merits and limitations of PSA should be discussed with all patients considering prostate cancer screening.

3066 Background: Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts (CAF), a major component of tumor stroma, confer treatment resistance, promote local progression, metastasis and immunosuppression. Because FAP is selectively expressed in the tumor stroma of many cancers, radiolabeled small molecule ligands targeting FAP are being explored for their use as pan-cancer theranostic agents. The objective was to establish the spectrum of FAP expression across various cancers by immunohistochemistry (IHC) and to explore whether 68Ga-FAPi-46 PET image biodistribution faithfully reflects tumor FAP expression from resected tumor and non-tumor specimens. Methods: This study was a prospective, exploratory, imaging trial in cancer patients. Referred volunteer patients scheduled to undergo surgical resection of the primary tumor and/or metastases were eligible. Patients underwent one whole body 68Ga-FAPi-46 PET/CT scan. Subsequently, patients underwent surgical resection of the primary tumor and/or metastasis. The outcome measure was the correlation of 68Ga-FAPi-46 PET maximum standardized uptake value (SUVmax) with FAP IHC score in patient-matched cancer and non-cancer tissue. Results: The frequency of FAP expression across 14 cancers on tissue microarrays ranged from 25 to 100% (mean 76.6±25.3%). For imaging and IHC correlation, fifteen patients with the following cancer types were prospectively included: colorectal (n = 4), head and neck (n = 3), pancreas (n = 2), breast (n = 2),stomach (n = 1), esophagus (n = 2) and uterus (n = 1). All 15 patients underwent surgery following their 68Ga-FAPi-46 PET scan within a mean time interval of 16.1±14.4 days (range 1 – 50 days). For two patients the tumor was deemed unresectable. 68Ga-FAPi-46 SUVmax and IHC scores were higher in cancer tissue than in normal tissue: mean 68Ga-FAPi-46 SUVmax 7.4±4.6 (range 1.5-15.9) vs 1.6±1.2 (range 0.4-5.1), (p < 0.001) and mean FAP IHC score 2.38±0.65 vs 0.54±0.66 (p < 0.001), respectively. The FAP IHC scores strongly correlated with 68Ga-FAPi-46 SUVmax (p = 0.001, repeated measures correlation r = 0.85 (95% CI 0.53-0.95), p < 0.001). Conclusions: 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlates with FAP tissue expression as measured by IHC. This translational validation paves the way for large scale prospective trials on the use of 68Ga-FAPi-46 PET/CT as a biomarker and stratification tool for FAP-targeted therapies. Clinical trial information: NCT04147494.