Faculty Bibliography

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

We followed two subjects with resected stage Ta superficial transitional cell carcinoma (TCC) of the bladder who had not received intravesicle bacillus Calmette-Guerin (BCG) and received supplementation with the agent Genistein Combined Polysaccharide (GCP) in an IRB approved study. The observation period was 12 months for both cases. After the yearly oral dosage of GCP, there was no recurrence in either of the subjects as determined by cytoscopy, urine cytology, and fluorescence in-situ hybridization analysis of urine (UrovysionTM FISH Assay). The intravenous pyelogram (IVP), obtained at baseline and after 12 months, was also negative. There were no adverse events over the course of treatment and had full patient compliance and tolerability of the GCP agent in both cases.

OBJECTIVE:To gather a pooled database from six tertiary-care referral centres using salvage cryotherapy (SC) for locally recurrent prostate cancer, and develop a pretreatment nomogram allowing a prediction of the probability of biochemical failure after SC, based on pretreatment clinical variables. PATIENTS AND METHODS/METHODS:We retrospectively analysed 797 men treated at six tertiary-care referral centres with SC for locally recurrent disease after primary radiotherapy with curative intent. The median duration of follow-up from the time of SC to the date of last contact was 3.4 years. The primary study endpoint was biochemical failure, defined as a serum prostate-specific antigen (PSA) level after SC of >0.5 ng/mL. RESULTS:Overall, the rate of biochemical failure was 66% with a median of 3.4 years of follow-up. A logistic regression model was used to predict biochemical failure. Covariates included serum PSA level at diagnosis, initial clinical T stage, and initial biopsy Gleason score. On the basis of these results, a pretreatment nomogram was developed which can be used to help select patients best suited for SC. Our pretreatment nomogram was internally validated using 500 bootstrap samples, with the concordance index of the model being 0.70. CONCLUSION/CONCLUSIONS:A pretreatment nomogram based on several diagnostic variables (serum PSA level at diagnosis, biopsy Gleason grade, and initial clinical T stage) was developed and might allow the selection of ideal candidates for SC.

OBJECTIVES/OBJECTIVE:To determine the safety, tolerability, maximal tolerated dose, and efficacy of a concentrated cranberry liquid blend, UTI-STAT with Proantinox, in female patients with a history of recurrent urinary tract infections (rUTIs). METHODS:The study agent was administered orally at 15, 30, 45, 60, and 75 mL daily for 12 weeks to women with a history of 2.78 ± 0.73 rUTIs <6 months. Blood and urine samples were collected at baseline and weeks 4 and 12. The women took daily doses of the agent. The primary endpoints were the safety, tolerability, and maximal tolerated dose. The secondary endpoints were the efficacy with regard to rUTI and quality-of-life (QOL) symptoms. RESULTS:A total of 28 subjects were included in the study. Of these 28 women, the data from 23 were analyzable. The average age was 46.5 ± 12.8 years. The maximal tolerated dose of UTI-STAT was 75 mL/d, and the recommended dose was set at 60 mL/d. The secondary endpoints demonstrated that only 2 (9.1%) of 23 reported a rUTI, a markedly better rate than the historical data. At 12 weeks, the reduction in worry about rUTIs and increased QOL with regard to the physical functioning domain and role limitations from physical health domain, as measured by the Medical Outcomes Study short-form 36-item questionnaire, were significant (P = .0097). A lower American Urological Association Symptom Index indicating greater QOL was also significant (P = .045). CONCLUSIONS:The novel concentrated cranberry liquid blend showed a good safety profile and tolerability in both pre- and postmenopausal women with history of rUTIs. The secondary endpoints demonstrated its effectiveness in reducing the incidence of rUTI and increasing QOL. Given this evidence, supplementation might be beneficial in the prevention of rUTIs in this population.

AIM/OBJECTIVE:To demonstrate the efficacy of PectaSol-C modified citrus pectin (MCP) on prostate cancer in vitro. METHOD/METHODS:Cytotoxicity analysis of PectaSol-C was performed by MTT assay, as were parallel studies with the former brand version of MCP called PectaSol. Apoptosis and inhibition of cell growth were investigated by Western blotting. RESULTS:Androgen-dependent and -independent human prostate cancer cell lines (LNCaP and PC3, respectively), androgen-dependent and -independent murine prostate cancer cell lines (CASP2.1 and CASP1.1, respectively), as well as noncancerous human benign prostate hyperplasia BPH-1 cell line, were used in the study. MTT assay revealed that 1.0% PectaSol exerted cytotoxicity on LNCaP, PC3, CASP2.1, CASP1.1, and BPH-1 cells for 4-day treatment by 48.0% +/- 2.1%, 54.4% +/- 0.3%, 15.4% +/- 0.8%, 46.1% +/- 1.7%, and 27.4% +/- 1.6%, respectively; whereas 1.0% PectaSol-C showed cytotoxity by 52.2% +/- 1.8%, 48.2% +/- 2.9%, 23.0% +/- 2.6%, 49.0% +/- 1.3%, and 26.8% +/- 2.6%, respectively. Western blotting further confirmed that both MCPs inhibit MAP kinase activation, increase the expression level of its downstream target Bim, a pro-apoptotic protein, and induce the cleavage of Caspase-3 in PC3 and CASP1.1 prostate cancer cells. CONCLUSION/CONCLUSIONS:PectaSol MCP and PectaSol-C MCP can inhibit cell proliferation and apoptosis in prostate cancer cell lines. Our data suggested that 1.0% PectaSol-C can be used for further chemopreventive and chemotherapeutic analysis in vivo.

INTRODUCTION/BACKGROUND:Ten-year disease-specific survival for clinically localized prostate cancer after radiation is 93%, 88%, and 80% for low-, medium-, and high-risk groups, respectively. The objective of this study was to report long-term cancer survival outcomes for patients who had undergone prostate cryotherapy at our institution more than 10 years ago. To date, this is the longest reported follow-up after cryotherapy. MATERIALS AND METHODS/METHODS:A retrospective patient chart review, conducted of an Institutional Review Board (IRB)- approved cryotherapy database, identified 76 men who had undergone prostate cryotherapy before January 1999. Pre-, intra-, and posttreatment data were collected. Primary study endpoints were overall mortality and prostate-cancer-specific death. Secondary endpoints were disease recurrence and clinical progression. RESULTS:Mean patient age was 69.2 (47.4-86.3) years; median preoperative prostate-specific antigen was 5.3 (0.2-208.0); mean Gleason score was 7. Forty of 76 (52.6%) were confirmed D'Amico high risk. Median follow-up was 10.1 (0.2-14.9) years; 25 patients underwent primary treatment; 51 postradiation. After 10 years of follow-up, 43 of 76 men (56.6%) were still alive; 33 men (43.4%) had died-10 (13.2%) from prostate cancer, 18 (22.4%) from noncancerous causes, and 5 (6.6%) unknown. CONCLUSIONS:The long-term results of prostate cryotherapy in our series indicate an 87% overall 10-year prostate-cancer-specific survival, despite early cryotherapy technology and the majority of patients being D'Amico high risk.

The anticancer effects of ProstaCaid, a novel integrative blend of vitamins, minerals, multiherb extracts, and derivatives, were tested in human and mouse androgen-dependent (AD) and -independent (AI) prostate cancer cell lines. ProstaCaid shows growth inhibitory effects on both human and mouse AD prostate cancer cells (LNCaP and CASP 2.1) and AI prostate cancer cells (PC3 and CASP 1.1) in a dose-/time-dependent manner. Consistently, long-term treatment with ProstaCaid also reduced colony formation capacities of prostate cancer cells. Flow cytometry assays revealed that ProstaCaid induces G2/M arrest and apoptosis in LNCaP and PC3 cells after 72 hours of treatment. Immunoblotting assay demonstrated that 25 microg/mL of ProstaCaid treatment resulted in (1) the reduction of cyclin D1, cyclin B1, and Cdc2 expression in a time-dependent way; (2) increase in p21(WAF1/Cip1) as early as 12 hours after the treatments in PC3 cells and reduction to base line at the 72-hour time point; and (3) repression of Bcl-2, BclxL, and induction of Bim as well as the cleavages of caspase-3 and poly(ADP-ribose) polymerase (PARP) at 72 hours of treatment, suggesting caspase-3-dependent apoptosis. Moreover, ProstaCaid suppressed activation of AKT and MAPK signaling pathways in PC3 and LNCaP cells by reducing phosphorylation levels of AKT, its downstream target S6 ribosomal protein and GSK3beta, and ERK1/2, respectively. In summary, these findings strongly suggest that ProstaCaid may be a potential chemopreventive and therapeutic agent for both AD and, more importantly, AI prostate cancer.

PURPOSE/OBJECTIVE:Focal cryoablation targets unilateral disease, sparing healthy tissue and the ipsilateral neurovascular bundle. Given half the prostate is spared, proper patient selection is imperative to optimize outcomes. We report focal cryotherapy outcome data and evaluate the accuracy of the 2007 Task Force patient selection criteria at predicting disease recurrence. MATERIALS AND METHODS/METHODS:This is a retrospective patient chart review from a single academic institution. Inclusion criterion is having unilateral prostate cancer treated with primary hemicryoablation. Patients were stratified using the Task Force selection criteria. Exclusion criterion is having had past radiation or hormone therapy. Progression-free survival was calculated using follow-up TRUS biopsy (biopsy done with transrectal ultrasound) and serial prostate-specific antigen (PSA) results (Phoenix criteria). Kaplan-Meier curves were constructed and Cox regression analyses performed, comparing outcomes across patient selection cohorts. RESULTS:From 2002 to 2009, 77 men underwent primary focal cryosurgery: mean age, 69.5 (SD, 6.7) years; median follow-up time, 24 months (range, 0-87 months); mean precryosurgical PSA, 6.5 (SD, 4.9) ng/mL; median Gleason score, 6 (range, 5-8). There were 44, 31, and 2 men who had D'Amico low-, intermediate-, and high-risk disease, respectively. Seventeen men met Focal Task Force Selection Criteria. After treatment, 22 patients underwent prostate biopsy for suspicion of recurrent disease. Of the 22 patients, 10 (45.5%) had confirmed prostate cancer. Of the 10 patients, 2 had ipsilateral disease, 7 had contralateral disease, and 1 had bilateral disease. Overall biochemical and pathological progression-free survival rates were 72.7% and 87%. The cumulative incidence of biochemical disease progression, using the Kaplan-Meier method, was greater than 75% at 3 years for men with more than 2 positive preoperative biopsy cores and greater than 50% at 5 years for men with 2 or less positive preoperative biopsy cores. No survival differences were seen across cohorts. Pretreatment PSA level, pretreatment Gleason score, number positive cores, and total tumor length were associated with disease progression. CONCLUSIONS:Focal cryotherapy is a promising option for carefully selected patients, although optimization of inclusion criteria is required. Current selection criteria are associated with cancer-free survival. Given no accurate definitions for biochemical failure after focal cryotherapy exist combined with our high biochemical failure rate, mandating 12-month follow-up TRUS biopsy may improve accurate detection of cancer progression. Further follow up will determine optimal patient selection criteria and follow-up protocols for patients undergoing primary focal unilateral nerve-sparing prostate cancer treatment.