Faculty Bibliography

BACKGROUND:Salvage cryosurgery (SC) is a recognised option for patients who fail either primary radiation or cryosurgery. OBJECTIVE:To report outcomes of patients undergoing SC. DESIGN, SETTING, AND PARTICIPANTS/METHODS:A consecutive series of 396 patients who had failed either primary radiotherapy or cryosurgery underwent SC between October 1994 and August 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Demographic and clinical parameters before primary and salvage treatment were evaluated; disease-free-survival (DFS), overall-survival (OS), disease-specific-survival (DSS), and complications were assessed. RESULTS AND LIMITATIONS/CONCLUSIONS:Sufficient follow-up data were available for 328 patients. Median age was 65.8 yr (range: 45-81 yr), median serum prostate-specific antigen (PSA) level was 8.0 ng/ml (range: 0.6-290.0 ng/ml). After primary treatment, median time to recurrence was 55 mo (range: 0.0-183.6 mo). SC was performed at a median of 67.5 mo (range: 7.0-212.7 mo) later; median pre-SC PSA level was 4.0 ng/ml (range: 0.1-112.4 ng/ml). Median PSA nadir was 0.2 ng/ml (range: 0.01-70.70 ng/ml), reached after a median of 2.6 mo (range: 2.0-67.3 mo) after SC. Median follow-up was 47.8 mo (range: 1.6-203.5 mo). Respective 5- and 10-yr DFS was 63% and 35%; OS: 74% and 45%; and DSS: 91% and 79%. In univariate analyses, time from primary treatment to SC or recurrence, PSA level before SC, and PSA nadir after SC were all significant predictors of recurrence (p ≤ 0.01). PSA before SC and time to recurrence were also predictive of DSS (p=0.003 and p=0.01, respectively). In multivariate analyses, only PSA nadir after SC was predictive of recurrence and DSS (p<0.001 and p=0.012, respectively). Complications were rare (range: 0.6-4.6%). Fifty-five patients (16.7%) underwent focal SC. Median PSA nadir after focal SC was 0.44 ng/ml (range: 0.04-20.1 ng/ml). Twenty-seven patients (49%) experienced recurrence. Respective 5- and 10-yr DFS was 47% and 42%; OS: 87% and 81%; and DSS: 100% and 83%. CONCLUSIONS:Our analysis confirms SC as an effective treatment option for patients failing primary therapy. Patients experienced excellent survival outcome and minimal associated morbidity after SC. Focal SC is an efficacious treatment for properly selected patients.

OBJECTIVE:To report on biochemical recurrence (BCR) and major complications in patients with prior prostate resection that underwent cryosurgery (CS) for prostate cancer. METHODS:The Columbia University Urologic Oncology database identified patients that underwent CS after resection. Patient demographics, surgical details, prostate volume, prostate-specific antigen (PSA) levels, biopsy results, major complications, and BCR were recorded. RESULTS:Prior resection for benign prostatic hyperplasia was identified in 32 patients who underwent CS. Median age was 70.7 years (range 54.9-83.1 years). Median prostate volume before and after resection was 40 (range 30-90) and 20 cm(3) (range 9-54), respectively. Median time from resection to CS was 50.4 months (range 0-178.1 months). Twenty-one (16 full and 5 focal gland ablations) and 11 patients underwent primary and salvage CS, respectively. Median prostate-specific antigen at CS was 5.9 ng/mL (range 0.1-18.4 ng/mL), with a median nadir post-CS of 0.1 ng/mL (range 0.04-12.2 ng/mL). Median follow-up was 41.2 months (range 8.9-154.2 months). According to Stuttgart and Phoenix definitions, 11 and 10 patients, respectively, experienced BCR. Three patients underwent further CS for disease recurrence. Overall complications were rare and minor. Patients with smaller glands postresection (<20 cc(3)) experienced a similar incidence of BCR as those with larger glands after CS in all the settings. CONCLUSION/CONCLUSIONS:Although no patients experienced major complications after primary CS, 18% (2/11) had grade III or higher complications in the salvage setting. Postresection gland volume was not associated with BCR. Further research is needed to evaluate functional and oncological outcomes in postresection patients after CS because they are considered high-risk for major complications.

BACKGROUND:The use of frameless robotic stereotactic body radiotherapy has not been investigated in patients whose primary cryosurgery treatment failed. The aim of this series was to present initial experiences with frameless robotic radiosurgery in the treatment of local prostate recurrence after cryotherapy. METHODS:We reviewed the outcome of frameless robotic radiosurgery in 4 patients for biopsy-proven local recurrent prostate cancer after cryotherapy. The patients underwent stereotactic body radiation therapy (SBRT) at Winthrop University Hospital, Mineola, New York. RESULTS:The patients' ages ranged from 66 to 75 years old. The average follow-up was more than 4 months. Presalvage prostate-specific antigen (PSA) levels were 7.3, 11.9, 6.1, and 20.9 ng/mL for the four patients. Presalvage Gleason scores were 7, 7, 9, and 8 respectively. One patient had insufficient follow-up for inclusion. The 3 remaining patients showed reduction of PSA levels after SBRT. Follow-up post-SBRT PSA levels were 2.2, 0.19, and 2.0 ng/mL. The average PSA reduction was 7.0 ng/mL. Morbidity at 3-week follow-up included urinary urgency, dysuria, and constipation. There was no change in international prostate symptom score or The International Consultation on Incontinence Questionnaire-Short Form scores after SBRT. One patient experienced erectile dysfunction from SBRT. CONCLUSIONS:Initial results indicate that robotic SBRT is a viable option for patients who have failed initial cryosurgery therapy measures. The patients had minimal morbidity with significant reduction in PSA levels.

BACKGROUND:Interference of androgen receptor (AR) signaling is a target for prostate cancer (CaP) chemoprevention and treatment. We hypothesize that Zyflamend (ZYF) assert its anti-cancer effect by disrupting AR signaling. We also hypothesize that it may act synergistically with the anti-androgen bicalutimde to inhibit CaP cell growth. METHODS:Western blotting, ELISA and reporter assays were done to test ZYF on AR signaling. Semi-quantitative RT-PCR and AR half-life were also examined. Potential synergism between ZYF and bicalutimide were tested via cytotoxicity, colony formation assays, flow cytometry, and Western blotting in the human CAP line, LNCaP and 22RV1. RESULTS:ZYF reduced AR protein, mRNA and protein stability levels in LNCaPs. ZYF also reduced both full-length AR protein and truncated AR protein in the 22Rv1 cell line. Nkx3.1 and PSA were also reduced at the mRNA level. PSA promoter activity and secretion were lower after treatment of cells with ZYF. DHT induction of cell proliferation and AR responsiveness revealed reduction of AR, Nkx3.1, and PSA protein were demonstrated with ZYF treatment. Co-treatment with bicalutimide reducing cell growth, induced apoptosis, and reduced Bcl-2 and BclxL, caspase-3 and PARP. Co-treatment also reduced Nkx3.1 and PSA protein. CONCLUSIONS:These data indicate that ZYF suppresses cell growth mediated by AR signaling, and suggests that the co-treatment with the anti-androgen bicalutimide and ZYF may be a promising approach for cancer therapy and may demonstrate the mechanism of action of ZYF.

BACKGROUND:Various definitions of biochemical failure (BF) have been used to predict cancer recurrence following prostate cryoablation. However to date, none of these definitions have been validated for this use. We have reviewed several definitions of BF to determine their accuracy in predicting biopsy-proven local recurrence following prostate cryoablation. METHODS:The Columbia University Urologic Oncology Database was queried for patients who underwent prostate cryoablation between 1994 and 2010, and who subsequently underwent surveillance biopsy due to clinical suspicion of prostate cancer recurrence. Serial postoperative prostate-specific antigen (PSA) results were used to determine BF according to various definitions of BF. Biopsy results were used to determine local recurrence. Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curve area were calculated for each of the BF definitions. RESULTS:A total of 110 patients met inclusion criteria for the study. These patients were treated with primary full-gland (n = 38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer. The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and 0.64, respectively. CONCLUSIONS:Overall, the Phoenix definition best predicted local cancer recurrence following prostate cryoablation. These preliminary data may be useful for researchers evaluating the short-term efficacy of cryoablation, and for urologists assessing their patients for potential cancer recurrence.

PURPOSE/OBJECTIVE:Vitamin D has a well-known role in calcium metabolism and bone health. It may also help prevent a number of chronic diseases, including cardiovascular disease, diabetes and malignancies such as breast, colorectal and prostate cancer. To our knowledge the prevalence of vitamin D deficiency has never been reported in the general urological population. We evaluated the vitamin D status of this population at a large academic center. MATERIALS AND METHODS/METHODS:We retrospectively reviewed the records of 3,763 male and female patients from a urology database at a single academic institution. Patients were identified whose levels of serum 25-hydroxyvitamin D were measured for the first time between 1997 and 2010. We determined the prevalence of normal--greater than 30, insufficient--20 to 29 and deficient--less than 20 ng/ml 25-hydroxyvitamin D. Logistic regression analysis was performed to identify risk factors for vitamin D deficiency. RESULTS:Overall 2,559 patients (68%) had suboptimal 25-hydroxyvitamin D (less than 30 ng/ml), of whom 1,331 (52%) were frankly deficient (less than 20 ng/ml) in the vitamin. Vitamin D deficiency was more common in patients younger than age 50 years (44.5%), black (53.2%) and Hispanic (41.6%) patients (p <0.001), and patients without an existing urological malignancy (35.4%, p <0.001). On multivariate analysis race, age, season and cancer diagnosis were independent predictors of vitamin D status. CONCLUSIONS:Vitamin D deficiency is extremely common in urological patients at a major urban medical center. Urologists should consider recommending appropriate supplementation during the initial assessment of all patients.