John Eifler

Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer.

The ideal treatment for men with high‐risk prostate cancer is controversial, although most physicians agree that a multimodal approach, including radiation and hormone therapy with or without surgery, offers the best chance of cancer control. Minimally‐invasive radical prostatectomy has emerged as a treatment option for clinically localized cancer; however, critics argue that the open approach may afford advantages of tactile feedback and a better lymph node dissection. The present study demonstrates that open and minimally‐invasive radical prostatectomy offer equivalent short‐term outcomes for men with high‐risk prostate cancer at a highly experienced centre.

Pelvic Lymph Node Dissection is Associated With Symptomatic Venous Thromboembolism Risk During Laparoscopic Radical Prostatectomy

PURPOSEnVenous thromboembolism is a potentially catastrophic complication of radical prostatectomy. It is unknown whether pelvic lymph node dissection is related to the development of venous thromboembolism. We hypothesized that omitting pelvic lymph node dissection may be associated with a decreased incidence of venous thromboembolism.nnnMATERIALS AND METHODSnThe records of 773 consecutive patients who underwent laparoscopic radical prostatectomy by a single surgeon from 2001 to 2009 were reviewed for postoperative venous thromboembolism. All patients underwent laparoscopic radical prostatectomy with or without pelvic lymph node dissection and had at least 3 months of followup. Generally only patients at increased risk for lymph node metastasis received pelvic lymph node dissection. Diagnostic studies were not routinely performed but were initiated for clinical symptoms of venous thromboembolism. Separately a meta-analysis of radical prostatectomy studies with or without pelvic lymph node dissection was performed to evaluate associations with venous thromboembolism.nnnRESULTSnOf the 773 patients 468 (60.8%) underwent laparoscopic radical prostatectomy plus pelvic lymph node dissection, 302 (39.2%) underwent laparoscopic radical prostatectomy without pelvic lymph node dissection, and 3 were missing preoperative data and were excluded from study. Patients in the laparoscopic radical prostatectomy plus pelvic lymph node dissection and laparoscopic radical prostatectomy only groups were similar in age, body mass index and prostate volume, although they differed in pathological characteristics and operative time. Venous thromboembolism occurred in 7 of 468 (1.5%) patients who underwent laparoscopic radical prostatectomy plus pelvic lymph node dissection and in 0 of 302 (0%) who underwent laparoscopic radical prostatectomy only (p = 0.047). Patients in whom venous thromboembolism developed had greater body mass index (30.8 vs 27.1 kg/m(2), p = 0.015) than those in whom venous thromboembolism did not develop. No patient had a symptomatic lymphocele. Meta-analysis of the literature demonstrated a significant association between venous thromboembolism and radical prostatectomy plus pelvic lymph node dissection compared to radical prostatectomy only (RR 2.15, CI 1.14-4.04, p = 0.018).nnnCONCLUSIONSnPelvic lymph node dissection during radical prostatectomy increases the risk of venous thromboembolism. In carefully selected low risk patients omitting pelvic lymph node dissection may decrease the incidence of venous thromboembolism.

Real-time, Near-Infrared Fluorescence Imaging with an Optimized Dye/Light Source/Camera Combination for Surgical Guidance of Prostate Cancer

Purpose: The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo. Experimental Design: We have developed and validated a laparoscopic imaging system (including an optimized light source, LumiNIR) that is capable of imaging small tumor burdens with minimal background fluorescence in real-time laparoscopic extirpative surgery of small prostate tumor xenografts in murine and porcine models. Results: In a mouse model, we demonstrate the feasibility of using real-time NIR laparoscopic imaging to detect and surgically remove PSMA-positive xenografts. We then validate the use of our laparoscopic real-time NIR imaging system in a large animal model. Our novel light source, which is optimized for YC-27, is capable of detecting as little as 12.4 pg/mL of the compound (2.48-pg YC-27 in 200-μL agarose). Finally, in a mouse xenograft model, we demonstrate that the use of real-time NIR imaging can reduce positive surgical margins (PSM). Conclusions: These data indicate that a NIR-emitting fluorophore targeted to PSMA may allow improved surgical treatment of human prostate cancer, reduce the rate of PSMs, and alleviate the need for adjuvant radiotherapy postoperatively. Clin Cancer Res; 21(4); 771–80. ©2014 AACR.

Ureteral Stents Placed at the Time of Urinary Diversion Decreases Postoperative Morbidity

Objective: To determine the impact of stenting ureteroenteric anastomoses on postoperative stricture rate and gastrointestinal recovery in continent and noncontinent urinary diversions (UDs). Patients and Methods: We retrospectively reviewed the clinical and pathologic data on 192 consecutive patients who underwent a radical cystectomy and UD. Patients received either a continent or noncontinent UD with or without stent placement through the ureteroenteric anastomoses. Stricture rate, gastrointestinal recovery, length of hospital stay, and stricture characteristics were analyzed. Study endpoints were compared between four groups – stented and nonstented continent and stented and nonstented noncontinent UDs. Results: 36% of patients were stented and 64% were nonstented at the time of UD. Total ureteral stricture rate was 9.9%. There was no statistically significant difference in stricture rate (p = 0.11) or length of hospital stay (p = 0.081) in stented compared to nonstented patients. There was a significantly (p = 0.014) greater rate of ileus in patients who were nonstented in both continent and noncontinent UDs. Conclusion: Stenting of ureteroenteric anastomoses in both continent and noncontinent UD has no effect on postoperative stricture rate, but is associated with lower rates of postoperative ileus.

Causes of death after radical prostatectomy at a large tertiary center.

PURPOSEnMost men treated with radical prostatectomy do not die of prostate cancer. We evaluated the cause of death in a large series of patients who underwent radical prostatectomy and compared the rate of death to that of the general American population.nnnMATERIALS AND METHODSnThe study population consisted of 18,209 men who underwent radical prostatectomy at our institution between 1975 and 2009. Close patient followup and a national database were used to identify which patients died and classify the cause of death. These data were compared with general American population data from the National Vital Statistics System.nnnRESULTSnMedian age at radical prostatectomy was 59 years (IQR 54.0-63.0). At a median followup of 7.4 years (IQR 3.7-11.9) 1,419 patients had died (7.8%), including 379 of prostate cancer. Actuarial 10 and 20-year overall survival rates after radical prostatectomy were 92.6% and 69.2%, respectively. The overall death rate was lower in men treated with radical prostatectomy than in the general American population (standardized mortality ratio 0.47, 95% CI 0.44-0.49). Differences were particularly pronounced for heart disease, chronic respiratory conditions, diabetes and infection. Of men who died of a nonprostate cancer cause 44.0% died of a secondary malignancy.nnnCONCLUSIONSnOverall survival after radical prostatectomy is excellent. Men who undergo radical prostatectomy usually die of a nonprostate cancer cause. Almost half of patients who survive prostate cancer die of a secondary malignancy, likely due to the selection of surgical candidates at low cardiopulmonary risk.

Focal positive prostate-specific membrane antigen (PSMA) expression in ganglionic tissues associated with prostate neurovascular bundle: Implications for novel intraoperative PSMA-based fluorescent imaging techniques

OBJECTIVEnProstate specific membrane antigen (PSMA) is primarily expressed in glandular prostatic tissue and is frequently utilized to detect primary or metastatic prostatic adenocarcinoma (CaP). A purported novel application of PSMA detection is the intraoperative real-time identification of CaP using radioimmunoscintigraphy to define the extension of the surgical resection. Considering that PSMA expression has been reported in other tissues, we evaluated its immunoexpression in prostatic neurovascular bundle elements to assess the convenience and safety of the aforementioned procedure.nnnMATERIALS AND METHODSnTwenty consecutive specimens of radical prostatectomy (RP) were retrieved from our surgical pathology archives. PSMA immunoexpression (Clone 3E6, DAKO) was assessed in a representative section from each specimen containing neurovascular bundle elements.nnnRESULTSnPSMA expression was documented in 20/20 of examined CaP slides. Most cases exhibited an apical/cytoplasmic or cytoplasmic with membranous accentuation pattern of staining. Focal weak to moderate cytoplasmic staining was detected in associated ganglionic tissue in 3/15 of the examined RP. In all cases, staining was cytoplasmic, less extensive, and weaker than the pattern observed in CaP. None of the peripheral nerve sheath cells or lymphovascular components of the examined neurovascular bundles were positive for PSMA.nnnCONCLUSIONSnWe found focal positive PSMA expression in the ganglionic cells of the prostatic neurovascular bundle. Our results suggest that the radioimmunoscintigraphic detection of radiolabeled PSMA antibodies might not be entirely specific for prostatic cells; this observation must be taken into account should an intraoperative PSMA-based fluorescent imaging technique be used to define the extension of the surgical procedure.

MP93-18 CAVERNOUS NERVE RECONSTRUCTION BY PROCESSED NERVE ALLOGRAFT DURING ROBOT-ASSISTED RADICAL PROSTATECTOMY

recurrence after radical prostatectomy (RP), due in part to underpowered cohorts and limited follow up. Herein, we evaluated the association between obesity and PCa recurrence after RP using a large institutional dataset with long-term follow-up. METHODS: We reviewed years 1987-2013 of the Mayo Clinic RP Registry to identify men with Body Mass Index (BMI) information available. Men who underwent PCa treatment prior to RP and men with metastatic disease at RP were excluded. Patients were grouped into four BMI categories: < 25, 25-29.9, 30-34.9, and > 35. BMI > 30 was defined as obese. Standard descriptive statistics compared baseline characteristics, while forced entry multivariable cox proportional hazard models assessed the association of BMI with metastasis and prostate cancer mortality (PCM). Multivariable models were adjusted for pre-RP PSA, pathologic Gleason Score, pT stage, pN stage, margin status, age, adjuvant hormone therapy, adjuvant radiation, year of surgery, and open vs robotic approach. RESULTS: In our cohort of 18,039 men (median follow-up 9.3 years after RP), 20.6% (3,707), 51.9% (9,348), 21.9% (3,936) and 5.6% (1,016) had a BMI < 25, 25-29.9, 30-34.9, and > 35, respectively. Higher BMI categories had higher rates of pathologic Gleason Score 7-10 disease: 38.7%, 40.7%, 46.1%, 54.0%, respectively (p<0.001). Obese patients also had higher positive margin rates: 23.4%, 26.3%, 30.1%, 31.9%, respectively (p<0.001). PSA, pT stage, pN stage, and adjuvant therapy did not significantly differ between BMI categories (p>0.05). Log Rank comparisons found higher Kaplan-Meier rates of metastasis and PCM for patients with a BMI of 30-34.9 and > 35 (p<0.05 for all). On multivariable cox regression for metastasis, patients with a BMI 30-34.9 (HR 1.307, 95% CI 1.0731.592, p1⁄40.008) and BMI > 35 (HR 1.421, 95% CI 1.071-1.886, p1⁄40.015) had an increased risk of metastasis relative to patients with a BMI < 25. Similarly, patients with a BMI 30-34.9 (HR 1.323, 95% 1.010-1.733, p1⁄40.042) and BMI > 35 (HR 1.620, 95% CI 1.098-2.392, p1⁄40.015) had higher PCM rates relative to patients with BMI < 25 on multivariable analysis. CONCLUSIONS: Our data supports an independent association between BMI and PCa metastasis and cancer-specific mortality after RP. There was a direct increase in the odds of metastasis and PCM between the BMI 30-34.9 and BMI > 35 groups, further strengthening this link. Further study is warranted to determine if weight loss can abrogate this effect of obesity on PCa recurrence after RP.

Abstract 3919: A preclinical model of laparoscopy demonstrating the feasibility of detecting PSMA positive cells with a NIR fluorophore (YC-27): implications for strategies to decrease positive margins during prostatectomy.

Introduction: Depending on the stage there is approximately a 4-54% positive surgical margin (+SM) following prostatectomy. Patients with +SM face the associated expense and impaired functional outcomes of salvage radiotherapy. To circumvent this, a low-molecular weight urea-based near infrared (NIR) fluorophore (YC-27) was developed to target the prostate specific membrane antigen (PSMA) for use in intraoperative imaging. PSMA is a transmembrane protein expressed in normal prostate and upregulated in cancer. PSMA expression correlates with Gleason score, advanced stage and PSA. We optimized dosing and timing in a small animal model for laparoscopic resection of PSMA positive tumors. Secondly, we demonstrate the feasibility of applying such a system in a porcine model. Methods: PSMA positive and negative tumors were established contralaterally on the flank of athymic male nude mice. YC-27 was administered intravenously at varying doses (9.5, 19.1, 39.7 [ug/Kg]) and sequentially imaged using a custom built laparoscopic system to obtain probe kinetics (1, 2, 3, 4, 6, 8, 10, 24 hrs post IV injection). Arbitrary pixel count was used to evaluate dosing and timing for signal to noise ratio. NIR guided laparoscopic resection was performed on mice with established PSMA positive and negative tumors 6 hrs post injection of 39.7 ug/Kg YC-27. In a porcine model, prestained human xenografts generated in a murine host were implanted behind the peritoneum of the abdominal cavity, and exploratory NIR laparoscopy was performed. In a porcine model, the kidney was observed with our laparoscopic NIR system after intravenous YC-27 administration. Results: In a murine model, the highest signal to noise ratio was determined to occur 6 hrs after injecting 39.7 ug/Kg YC-27. Using these parameters, NIR guided laparoscopic surgery facilitated full resection of the xenograft. In a porcine model, exploratory laparoscopy with our NIR system allowed detection of a prestained tumor implanted behind the peritoneum. In another experiment, strong fluorescent signal was observed from the porcine kidney immediately after IV injection of YC-27 which may be attributed to specific binding to PSMA, renal clearance, or a combination of both. Conclusions: YC-27 allows intraoperative localization of PSMA in real time using a prototype NIR guided laparoscopic surgical system. Pilot studies in large animals demonstrated excellent potential for clinical translation. Citation Format: Brian P. Neuman, John B. Eifler, Mark Castanares, Wasim H. Chowdhury, Ying Chen, Martin G. Pomper, Ronald Rodriguez. A preclinical model of laparoscopy demonstrating the feasibility of detecting PSMA positive cells with a NIR fluorophore (YC-27): implications for strategies to decrease positive margins during prostatectomy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3919. doi:10.1158/1538-7445.AM2013-3919

Erratum: An updated prostate cancer staging nomogram (partin tables) based on cases from 2006 to 2011 (BJU International 111 (22-29))

A typographical error was identified in Table 2, for the cell corresponding to the probability for EPE in a man with clinical stage T1c, PSA > 10, and biopsy Gleason 4 + 3. The cell should read “38 (32–45)” rather than “28 (32–45).” Also, in the third paragraph of the Results section, the fourth sentence should be changed to “In contrast, the predicted risk of LN+ is no more than 3% for T1c tumours with biopsy Gleason score < 9 for an PSA below 10.”

Patient Selection for Active Surveillance

Due to a long natural history, the majority of men diagnosed with prostate cancer in the current era would never die of disease if left untreated. Unfortunately, a potentially lethal tumor cannot be reliably distinguished from an insignificant tumor with certainty. As a result, urologists have developed strategies to monitor carefully selected men with favorable risk prostate cancer, with curative intervention in the event of disease progression: active surveillance. This chapter focuses on the selection of appropriate candidates for active surveillance.