A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy.

Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) µmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) µmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) µmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) µmol/l ( - 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.

Upper and middle trunk brachial plexopathy after robotic prostatectomy.

We describe 3 patients who developed injury of upper and middle brachial plexus trunks during robotic-assisted prostatectomy, and review factors potentially associated with this type of injury. Three patients underwent robotic-assisted prostatectomy. Surgical exposure was facilitated by steep head-down tilt position. To secure patients and prevent sliding on the operating table, shoulders were supported with moldable beanbags. In all 3 cases, the left arm was abducted to approximately 90°, and the right arm was adducted. Postoperatively, all patients were diagnosed with left arm upper and middle trunk brachial plexopathies. The combination of arm abduction, extreme head-down position, and shoulder immobilization with beanbags resulted in several mechanistic forces that may have contributed to the development of brachial plexopathy in our patients. Steep head-down tilt may result in cephalad slide of the torso in relation to an abducted arm. When shoulder restraints are used to secure the patient, the compensatory movement of the shoulder girdle of an abducted arm is impeded. This may result in injurious stretching and compression of the brachial plexus, especially the upper and middle trunks. When steep head-down position is needed to facilitate surgical exposure, clinicians should consider adduction and tucking of both arms, and use of other methods to prevent sliding on the operating room table that do not require the use of restraints across the shoulder girdle.

Quality of lymphadenectomy is equivalent with robotic and open cystectomy using an extended template.

PURPOSE: Extended lymph node dissection for bladder cancer provides better staging, cancerous node removal and potentially survival. Minimally invasive techniques have been criticized about the ability to adequately perform extended lymph node dissection. We compared the extended lymph node dissection quality of robotic and open cystectomy by assessing node yield and positivity. MATERIALS AND METHODS: We compared extended lymph node dissection in 120 open and 35 robotic cystectomy cases. Extended lymph node dissection included skeletonization of structures in each nodal group below the aortic bifurcation (common iliac, external iliac, obturator, hypogastric and presacral nodes). Nodes were processed identically but submitted as 1 or 2 packets for robotic cases and as 10 or more packets for open surgery cases. RESULTS: The mean±SD node count in the open group was 36.9±14.8 (range 11 to 87) and in the robotic group the mean yield was 37.5±13.2 (range 18 to 64). Only 12 of 120 open (10%) and 2 of 35 robotic (6%) cases had fewer than 20 nodes. A total of 36 open (30%) and 12 robotic (34%) cases were node positive. Open extended lymph node dissection identified 80% and 90% confidence of accurate staging as pN0 when obtaining 23 and 27 nodes, respectively. A node count of 23 or 27 was achieved in 87% and 77% of open cases, and in 91% and 83% of robotic cases, respectively. Of patients with open surgery 36% received neoadjuvant chemotherapy compared to 31% of those with robotic surgery. CONCLUSIONS: No difference was identified in the lymph node yield or the positive node rate when comparing open and robotic extended lymph node dissection. Local recurrence and survival data are needed to confirm whether the 2 techniques are oncologically equivalent.

Presacral and retroperitoneal lymph node involvement in urothelial bladder cancer: results of a prospective mapping study.

PURPOSE: We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. MATERIALS AND METHODS: As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. RESULTS: A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). CONCLUSIONS: A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.

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

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

Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management.

OBJECTIVE: To report changes in grade and stage between initial diagnostic and repeat biopsies or resection for urothelial carcinoma (UTUC) and investigate the consequences for endoscopic management. Ureteroscopic management of upper tract UTUC is an alternative to nephroureterectomy, which is less invasive and preserves renal function. However, concerns about potential understaging, inaccurate grading, incomplete resection, lack of effective tertiary chemoprevention, and need for ureteroscopic surveillance limits it appeal. METHODS: Clinicopathological records of patients with UTUC treated at our institution were reviewed. Fifty-six patients with a histologic diagnosis of UTUC and 2 or more consecutive biopsies or biopsy followed by surgical resection were included, resulting in 65 biopsy specimens. RESULTS: The median interval between diagnostic biopsy and subsequent biopsy or resection was 6 weeks (range, 1 week to 60 months). Change in grade from the diagnostic biopsy occurred in 24 of 65 biopsies (37%), including 9 in which diagnosis changed from low to high grade. Change in the stage from the diagnostic biopsy occurred in 25 of 65 biopsies (38%). Overall, 24 (43%) patients were reclassified from low-grade, noninvasive disease to high-grade and/or invasive disease. CONCLUSION: A change in grade and/or stage from the diagnostic biopsy occurred in more than one third of patients with UTUC managed conservatively. Because of the short median time interval between biopsies, this finding likely represents variability in tumor sampling on biopsy. Because of the concerns of undergrading and understaging, appropriate patient selection and vigilant endoscopic surveillance are mandatory for UTUC managed endoscopically.

Neoadjuvant systemic therapy or early cystectomy? Single-center analysis of outcomes after therapy for patients with clinically localized micropapillary urothelial carcinoma of the bladder.

OBJECTIVES: To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is a rare variant of urothelial carcinoma with aggressive clinical behavior. Radical cystectomy is considered the standard approach for treatment of patients with localized disease; however, the role of perioperative systemic therapy has been poorly defined. MATERIAL AND METHODS: A retrospective review identified 38 consecutive patients who had been treated at our institution for MPBC from 2000 to 2010. The patient data were analyzed for the pre- and postoperative clinicopathologic features, treatment course, and cancer-specific survival. RESULTS: The median follow-up of surviving patients after cystectomy was 17 months (range 2-75). At the initial transurethral biopsy, 28 patients (74%) had clinical Stage T2N0 or less. In this group, 26 (93%) of 28 were upstaged to nonorgan-confined and/or lymph node-positive disease. Overall, 32 patients (86%) had evidence of lymph node metastasis on the final pathologic examination. All patients with cTis-T1 who had undergone initial bladder-sparing therapy with bacille Calmette-Guérin had pathologically advanced disease at cystectomy. All 15 patients who had received perioperative cisplatin-based chemotherapy died of metastatic disease. The 5-year overall survival rate was 40% (95% confidence interval 16-64). CONCLUSIONS: MPBC is an aggressive disease with a high likelihood of regional lymph node metastasis at the initial presentation. Although radical cystectomy plays a critical role in treatment, systemic neoadjuvant chemotherapy might be a more appropriate strategy than immediate cystectomy. Because of the poor response to current chemotherapy agents, the development of new and effective drugs for this subset of patients could be needed.

Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy.

BACKGROUND: The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under-developed, this has important implications on patients' ability to receive cisplatin-based combination chemotherapy (CBCC). METHODS: Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m(2) was used to determine the presence of CKD and eligibility for CBCC. RESULTS: Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m(2). Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2-pT4 and/or pN1-pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively. CONCLUSIONS: CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high-risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy.

Aggregate lymph node metastasis diameter and survival after radical cystectomy for invasive bladder cancer.

OBJECTIVES: The current tumor-node-metastasis (TNM)-staging system for urothelial carcinoma of the bladder (UCB) is based on the number and size of the largest positive lymph node (LN). The aggregate LN metastasis diameter (ALNMD) may better reflect the burden of metastatic disease and improve the ability to predict recurrence-free (RFS) and overall survival (OS). METHODS: Clinical characteristics and follow-up information of 134 patients with LN-positive UCB treated by radical cystectomy was modeled using Cox proportional hazards regression analysis to predict OS. Pathologic specimens were retrospectively reviewed by a single genitourinary pathologist unaware of treatment outcome to determine the greatest dimension of metastasis in all affected LN. The median follow-up of survivors was 23 months. RESULTS: The median OS was 17 months; median LN density, 17%; and median number of LN removed, 14. ALNMD was a significant predictor of RFS and OS after adjusting for pathologic T stage, lymphovascular invasion, LN density, comorbidity, and extranodal extension (adjusted HR 1.1; P = .02), even when restricting the analysis to patients in whom 10 or more LN have been removed. The predictive accuracy of a model for OS that contained ALNMD was superior to the one without this parameter and the TNM-staging system (c-index 0.71 vs 0.67 vs 0.62). CONCLUSIONS: ALNMD is a significant predictor of RFS and OS after adjusting for standard prognostic parameters among patients with LN-positive UCB and may be a useful parameter to include in future predictive nomograms and TNM-staging systems.

How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage?

PURPOSE: Determining pathological nodal stage in patients with bladder cancer is important for prognosis. We determined how the extent of lymphadenectomy and the lymph node count influence accurate nodal staging. MATERIALS AND METHODS: The study included 120 patients who underwent at least extended lymphadenectomy at radical cystectomy. Different anatomical templates for lymphadenectomy were evaluated for nodal staging accuracy. The cumulative percent was plotted to determine a lymph node count that confidently identified node positive cases. RESULTS: The mean +/- SD total lymph node count in the study population was 36.9 +/- 14.8 at extended lymphadenectomy. Of the patients 36 (30%) had lymph node metastasis, including 14 (39%) with metastasis involving the common iliac and/or presacral lymph nodes. Limited, standard and extended lymphadenectomy accurately identified 75%, 88.9% and 100% of node positive cases, respectively. Removing 23 and 27 lymph nodes provided 80% and 90% confidence, respectively, that a case was accurately staged as pN0. No patient had lymph node metastasis above the aortic bifurcation without nodal metastasis below the aortic bifurcation and none had a change in pN stage by extending lymphadenectomy above the aortic bifurcation. CONCLUSIONS: To accurately identify node positive and negative cases, and correctly assign pN stage in node positive cases it is necessary to perform extended lymphadenectomy. Identifying at least 23 to 27 lymph nodes on final pathological evaluation provides a high level of confidence that a case is correctly staged as node positive or negative.

Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder: a contemporary series.

BACKGROUND: The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting. METHODS: From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle-invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database. RESULTS: Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3-4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle-invasive bladder cancer to RC was 208 days (interquartile range, 149 days -327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0 patients-17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43 patients-81 patients) had nonorgan-confined residual cancer, and the overall median progression-free survival was 10.5 months (95% CI, 7 months -14 months). CONCLUSIONS: Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non-MVAC-based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC.

Preoperative hydronephrosis as an indicator of survival after radical cystectomy.

OBJECTIVE: We determined the prognostic significance of preoperative hydronephrosis in patients with transitional cell carcinoma (TCC) of the bladder undergoing radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of all patients undergoing radical cystectomy at a single institution from 1996 to 2006. Exclusion criteria included diagnosis other than TCC, upper tract TCC, incomplete medical records, or obstructing stones. Hydronephrosis was confirmed by radiographic imaging. Survival was determined by date of death or last clinic visit. RESULTS: Three hundred eight patients fulfilled the inclusion criteria; 203 (66%) had normal upper tracts, 82 (27%) had unilateral hydronephrosis, and 23 (7%) had bilateral hydronephrosis. Median overall survival of the study population was 34.3 months. There was a statistically significant difference in median survival between those without hydronephrosis (46.3 months), and those with unilateral (18.6 months, P = 0.004) or bilateral (13.4 months, P < 0.001) hydronephrosis. Preoperative hydronephrosis was significantly associated with higher pT stage (P < 0.001) as well postoperative positive margins (P = 0.039), but not with positive lymph nodes (P = 0.086). Preoperative hydronephrosis had no significant effect on survival in patients with pT0-3a, N0, surgical margin negative tumors, but was significantly correlated with decreased survival in patients with pT3b or greater, or N+, or surgical margin positive tumors (median survival 12.8 months vs. 23.4 months, P = 0.011). On multivariate analysis, preoperative hydronephrosis was a significant predictor of decreased survival. CONCLUSIONS: Preoperative hydronephrosis is an important and independent prognostic variable in patients with TCC of the bladder treated with radical cystectomy.

Analysis of T1c prostate cancers treated at very low prostate-specific antigen levels.

BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) has challenged the validity of recommended prostate-specific antigen (PSA) thresholds for prostate biopsy (> 2.5 ng/ml) given the 17% prostate cancer (pCA) detection rate at PSA of 1.1-2.0. The outcome of patients treated at PSA < or = 2.5 is poorly defined, and advantages associated with such an early diagnosis are uncertain. OBJECTIVE: Compare the outcome of patients with T1c pCA with pretreatment PSA < or = 2.5 and 2.6-4.0. DESIGN, SETTING, AND PARTICIPANTS: Since 1998, 351 patients with clinical stage T1c and PSA < or = 4.0 have been treated at our institution; 84 (24%) of those patients had PSA < or = 2.5. Clinical information was obtained from a prospective database. Treatment was radical prostatectomy (RP), brachytherapy, and external-beam radiotherapy (EBRT) in 261 (74%), 67 (19%), and 23 (7%) patients, respectively. INTERVENTION: Definitive therapy for clinically localized pCA. MEASUREMENTS: Progression-free probability and pathologic end points. RESULTS AND LIMITATIONS: No significant differences between the groups were observed in terms of biopsy (18% vs 22%) or specimen Gleason score 7-8 (44% vs 56%), non-organ-confined cancer (11% vs 13%), indolent cancer (34% vs 24%), or 5-yr progression-free probability (89% vs 93%; p>0.1 for all). More biologically unimportant cancers (defined as pathologically organ-confined and Gleason < or = 6) were identified among patients with PSA < or = 2.5 (55% vs 41%, p=0.050), and indolent cancers were three times more frequent than non-organ-confined cancers among these patients (p=0.003). CONCLUSIONS: The pathologic features and outcome of patients treated at low PSA levels are favorable and similar for patients with PSA < or = 2.5 versus 2.6-4.0. However, > 50% of the former have potentially biologically unimportant cancer. We failed to identify a therapeutic benefit to the diagnosis of cancers below accepted PSA thresholds for biopsy.

A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen.

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.

Panniculectomy concurrent with anterior pelvic exenteration for recurrent cervical cancer.

BACKGROUND: Panniculectomy concurrent with gynecologic cancer surgery is safe and facilitates pelvic exposure in the morbidly obese patient. CASE: A 41-year-old morbidly obese female is diagnosed with recurrent adenocarcinoma of the cervix and has previously been treated with teletherapy and brachytherapy. She undergoes an anterior pelvic exenteration for curative intent. CONCLUSION: Panniculectomy at the time of pelvic exenteration is feasible. Morbidly obese patients with recurrent cervical cancer after treatment with pelvic radiation should be considered candidates for curative surgery.

Prostate-sparing cystectomy: has Pandora's box been opened?

En bloc removal of the prostate has traditionally been an integral component of radical cystectomy for men with bladder cancer owing to a high incidence of occult prostatic malignancy. However, the risk of functional morbidity following this procedure is considerable and can delay patient acceptance of cystectomy, which can adversely affect the long-term prognosis. Recently, some investigators have advocated prostate-sparing cystectomy (PSCx) to improve postoperative continence and potency rates, and this may also improve timely patient acceptance of cystectomy. Several of these PSCx series describe excellent functional results postoperatively and PSCx may also facilitate a laparoscopic approach, offering further dividends. However, valid concerns regarding the oncologic efficacy of this procedure still predominate and protocols for patient selection, technique and postoperative surveillance are not well defined. The concept of PSCx is arguably one of the most controversial topics in the field of bladder cancer today.

Targeted elimination of prostate cancer by genetically directed human T lymphocytes.

The genetic transfer of antigen receptors is a powerful approach to rapidly generate tumor-specific T lymphocytes. Unlike the physiologic T-cell receptor, chimeric antigen receptors (CARs) encompass immunoglobulin variable regions or receptor ligands as their antigen recognition moiety, thus permitting T cells to recognize tumor antigens in the absence of human leukocyte antigen expression. CARs encompassing the CD3zeta chain as their activating domain induce T-cell proliferation in vitro, but limited survival. The requirements for genetically targeted T cells to function in vivo are less well understood. We have, therefore, established animal models to assess the therapeutic efficacy of human peripheral blood T lymphocytes targeted to prostate-specific membrane antigen (PSMA), an antigen expressed in prostate cancer cells and the neovasculature of various solid tumors. In vivo specificity and antitumor activity were assessed in mice bearing established prostate adenocarcinomas, using serum prostate-secreted antigen, magnetic resonance, computed tomography, and bioluminescence imaging to investigate the response to therapy. In three tumor models, orthotopic, s.c., and pulmonary, we show that PSMA-targeted T cells effectively eliminate prostate cancer. Tumor eradication was directly proportional to the in vivo effector-to-tumor cell ratio. Serial imaging further reveals that the T cells must survive for at least 1 week to induce durable remissions. The eradication of xenogeneic tumors in a murine environment shows that the adoptively transferred T cells do not absolutely require in vivo costimulation to function. These results thus provide a strong rationale for undertaking phase I clinical studies to assess PSMA-targeted T cells in patients with metastatic prostate cancer.

Tomatoes, lycopene and prostate cancer: a clinician's guide for counseling those at risk for prostate cancer.

Prostate cancer has become a major public health issue and the search for etiologic risk factors and the development of chemopreventive agents has gained momentum over the last decade. An important epidemiologic finding has been the association between the consumption of tomato products and a lower risk of prostate cancer. Several investigators have proposed that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Laboratory and clinical studies have been initiated with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate cancer. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound may possibly reduce prostate cancer risk.

Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15.

The genetic transfer of antigen receptors provides a means to rapidly generate autologous tumor-reactive T lymphocytes. However, recognition of tumor antigens by cytotoxic T cells is only one step towards effective cancer immunotherapy. Other crucial biological prerequisites must be fulfilled to expand tumor-reactive T cells that retain a functional phenotype, including in vivo cytolytic activity and the ability to travel to tumor sites without prematurely succumbing to apoptosis. We show that these requirements are met by expanding peripheral blood T cells genetically targeted to the CD19 antigen in the presence of CD80 and interleukin-15 (IL-15). T cells expanded in the presence of IL-15 uniquely persist in tumor-bearing severe combined immunodeficiency (SCID)-Beige mice and eradicate disseminated intramedullary tumors. Their anti-tumor activity is further enhanced by in vivo co-stimulation. In addition, transduced T cells from patients with chronic lymphocytic leukemia (CLL) effectively lyse autologous tumor cells. These findings strongly support the clinical feasibility of this therapeutic strategy.