Prostatic Neoplasms: Cookson MS

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM, Anonymous00324. · American Urological Association Education and Research, Inc. · J Urol. · Pubmed #17509297 No free full text.

This publication has no abstract.

Dahm P, Yeung LL, Chang SS, Cookson MS. · Department of Urology, University of Florida, College of Medicine, Gainesville, Florida, USA. · J Urol. · Pubmed #18550100 No free full text.

Abstract: PURPOSE: Increasingly there is a recognized need for the development of high quality, evidenced-based clinical guidelines to assist clinicians and patients in critically important treatment related decision making. We review the different approaches used by leading urological organizations to develop guidelines for the management of clinically localized prostate cancer and their specific recommendations for case management. MATERIALS AND METHODS: Guidelines for the management of localized prostate cancer developed by leading professional organizations were identified through the National Guidelines Clearinghouse, PubMed, cited references and personal communication with prostate cancer experts. A structured data abstraction was applied to assess how the guideline was developed, what type of professionals and stakeholders were involved in the development process, how the primary evidence was identified and graded, and what specific final recommendations were reported. RESULTS: Clinical practice guidelines on the management of clinically localized prostate cancer demonstrate major differences in their specific recommendations. Few recommendations are based on high level evidence, and there are considerable discrepancies among the systems used to grade the quality of the evidence and the strength of the recommendations. CONCLUSIONS: There appears to be a need to standardize the process used by leading urological organizations to develop clinical guidelines for the management of prostate cancer. A unified approach may offer considerable rewards in terms of efficiency, guideline credibility and optimal clinical decision making. Furthermore, increased efforts are indicated to promote studies that yield high quality evidence to guide the management of prostate cancer.

Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, Anonymous00008. · The Johns Hopkins Hospital, 600 North Wolfe St., Marburg 407, Baltimore, Maryland 21287-2411, USA. · J Urol. · Pubmed #17570435 No free full text.

Abstract: PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Kaufman MR, Baumgartner RG, Anderson LW, Smith JA, Chang SS, Herrell SD, Cookson MS. · Department of Urologic Surgery, Vanderbilt University, Nashville, TN, USA. · BJU Int. · Pubmed #17309550 No free full text.

Abstract: OBJECTIVE: To assess reports supporting the novel and comprehensive evidence-based pathway for radical prostatectomy (RP), as collaborative-care pathways have helped to optimize management of patients treated with RP and such clinical pathways provide an ideal framework for constructing an original evidence-based pathway for the complete peri-operative care of these patients. PATIENTS AND METHODS: We searched for articles on Medline via PubMed to identify reports describing consensus opinions on appropriate aspects of the peri-operative management of patients treated with RP, specifically seeking to discern information on preoperative antibiotic regimen, peri-operative laboratory testing, use of beta-blockers for those at cardiac risk, pulmonary treatment, deep venous thrombosis prophylaxis, diet advancement, pain management, anti-emetic use, bowel regimen, and catheter removal after RP. RESULTS: Available reports were used to substantiate each variable of our collaborative-care pathway for RP. When available, meta-analyses were used to provide a broad review of the recognized clinical research. Otherwise, many controlled studies and retrospective reviews were relied upon to provide evidence to construct a framework for clinical decision-making. CONCLUSIONS: This is the first pathway for the peri-operative management of major urological procedure that is well integrated into current literature. The critical aspects of clinical decision-making in the patient treated with RP were validated by the available research.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · J Urol. · Pubmed #17222629 No free full text.

Abstract: PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Chang SS, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · Urology. · Pubmed #16904428 No free full text.

This publication has no abstract.

Kasper S, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA. · Urol Clin North Am. · Pubmed #16631458 No free full text.

Abstract: Advanced and metastatic prostate cancers remain potentially lethal tumors. Although androgen deprivation therapy remains the most effective treatment, patients who progress to androgen independence die of their disease. This article focuses on the mechanisms by which hormone resistance develops, including the reactivation of androgen receptor during androgen deprivation therapy, the role of cancer stem cells, and the emergence of epithelial-mesenchymal transition cells, which have increased metastatic potential. It is through an enhanced understanding of these mechanisms that new therapies can be developed to combat this disease.

Cookson MS. · Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · Mol Urol. · Pubmed #11062362 No free full text.

Abstract: Over the past decade, the sextant biopsy technique has emerged as the standard of care in the detection of prostate cancer. This technique is easy to learn and well tolerated by patients and has a major complication rate of <1%. However, limitations in cancer detection have been appreciated, particularly a false-negative rate approaching 25%. This high failure rate has led investigators to refine biopsy techniques to improve cancer detection. Intuitively, increasing the total number of cores should improve cancer detection. However, the optimal core number has yet to be defined. Confounding factors include variability of prostate size, tumor volume, and tumor location. Currently, a new standard is emerging prescribing a minimum of eight cores, of which at least three are directed at the lateral aspect of the peripheral zone. These additional biopsies appear to enhance cancer detection by about 15%. The improved yield is most pronounced among patients with a serum prostate specific antigen concentration between 4 and 10 ng/mL and larger gland volume (>50 cc). These additional biopsies may decrease the need for repeat biopsies. In the meantime, strategies are being developed for the optimal technique of repeat biopsies among patients with persistent clinical suspicion in the setting of a prior negative biopsy. Currently, recommendations include increasing the biopsy number to a minimum of 10 cores, including sampling of the lateral peripheral and transition zones.

Kibel AS, Rosenbaum E, Kattan MW, Picus J, Dreicer R, Klein EA, Chatta GS, Nelson JB, DiPaola RS, Roth BJ, Cookson MS, Wilding G, Jarrard DF, Beer TM, Ryan CW, Petrylak DP, Benson MC, Partin AW, Garrett-Mayer E, Eisenberger MA. · Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63105, USA. · J Urol. · Pubmed #17437819 No free full text.

Abstract: PURPOSE: Patients with adverse pathological features are at high risk for recurrence following radical prostatectomy. To improve outcomes in this population we performed a phase II study of adjuvant docetaxel in these high risk patients. MATERIALS AND METHODS: Patients with nonmetastatic radical prostatectomy at greater than 50% risk for recurrence by 3 years were eligible. Pathological findings were centrally reviewed and risk assessment was based on a validated multivariate Cox proportional hazards model. Treatment consisted of 6 cycles of 35 mg/m(2) docetaxel weekly given 4 to 12 weeks following surgery. Progression was defined as a prostate specific antigen of 0.4 ng/ml or greater, radiological/pathological evidence of recurrent disease or death from any cause. To screen for the potential benefit of adjuvant weekly docetaxel we used nomogram predicted progression-free survival as a historical control. RESULTS: A total of 77 patients were registered between April 2002 and January 2004. Two patients had grade IV hyperglycemia and 20 had grade III toxicity. At a median followup of 29.2 months (range 1.6 to 39.2) 46 of 76 evaluable cases (60.5%) progressed. Observed median progression-free survival was 15.7 months (95% CI 12.8-25.1). Predicted median progression-free survival in a matched population was 10 months. Seven patients died, including 4 of prostate cancer, 1 with intra-abdominal bleeding during treatment and 2 of pneumonia and sudden cardiac death, respectively, following treatment. CONCLUSIONS: Adjuvant docetaxel for prostate cancer is feasible with significant reversible but acceptable toxicity. The actual median progression-free survival of 15.7 months was longer than the nomogram predicted rate for this patient population. Adjuvant docetaxel treatment should be further evaluated in phase III trials in patients with high risk prostate cancer.

Webster TM, Herrell SD, Chang SS, Cookson MS, Baumgartner RG, Anderson LW, Smith JA. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · J Urol. · Pubmed #16093986 No free full text.

Abstract: PURPOSE: Laparoscopic prostatectomy, whether or not coupled with robotic assistance, is often considered less invasive than open radical retropubic prostatectomy (RRP). Minimal postoperative pain has been reported following robot assisted laparoscopic prostatectomy (RALP) but there have been few comparative studies with RRP. We compared perioperative narcotic use and patient reported pain in a prospective patient series. MATERIALS AND METHODS: Between June 2003 and May 2004, 314 patients underwent radical prostatectomy at our institution, including RALP in 159, RRP in 154 and conversion in 1. All patients were treated on a postoperative clinical pathway that included 30 mg ketorolac intravenously immediately postoperatively, followed by 15 mg intravenously every 6 hours. No regional anesthesia (epidural/spinal) narcotics or patient controlled analgesic pumps were used. All narcotic use was converted to morphine sulfate equivalents for purpose of analysis. A Likert scale of 0 to 10 was used to assess pain on the day of surgery, and on postoperative days 1 and 14. RESULTS: The total mean morphine sulfate equivalent +/- SD in patients in the RALP and RRP groups was low and, when corrected for length of stay, it was not statistically different (22.41 +/- 1.13 vs 23.01 +/- 1.16 mg, p = 0.72). Mean Likert pain perception scores were low at all time points in the RALP and RRP groups but statistically lower on the day of surgery in the RALP cohort (2.05 +/- 1.99 vs 2.60 +/- 2.25, p = 0.027). Patient reported mean pain scores were almost identical for RALP vs RRP on postoperative days 1 (1.76 +/- 1.87 vs 1.73 +/- 1.77, p = 0.880) and 14 (2.51 +/- 1.91 vs 2.42 +/- 1.84, p = 0.722). CONCLUSIONS: Perioperative narcotic use and patient reported pain are low regardless of the surgical approach used for radical prostatectomy. RALP did not provide a clinically meaningful decrease in pain compared with RRP, primarily because of the low pain scores reported in each group. Outcomes other than pain will ultimately determine the role of laparoscopic radical prostatectomy and RALP.

Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER, Wells N, Smith JA. · Department of Urologic Surgery, Vanderbilt University, Nashville, TN, USA. · J Urol. · Pubmed #12478123 No free full text.

Abstract: PURPOSE: The low rate of pelvic node metastasis in most contemporary series of patients undergoing radical prostatectomy for carcinoma of the prostate has been attributed to earlier and better patient selection than historical series. Alternatively, it has been suggested that the limited dissection commonly performed misses nodal metastasis in a substantial number of patients. To assess the value of an extended node dissection in detecting nodal metastasis, we performed a randomized prospective study. MATERIALS AND METHODS: A total of 123 patients undergoing radical prostatectomy were randomized to an extended node dissection on the right versus the left side of the pelvis with the other side being a limited dissection. The extended dissection included removal of all external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. The limited dissection included only the nodes along the external iliac vein and obturator nerve. RESULTS: Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p = 0.08). CONCLUSIONS: Extended node dissection in contemporary series of patients undergoing radical prostatectomy identifies few with nodal metastases not found by a more limited dissection. A trend toward an increased risk of complications attributable to the lymphadenectomy occurs with an extended dissection.

Fowke JH, Motley SS, Smith JA, Cookson MS, Concepcion R, Chang SS, Byerly S. · Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee 37203-1738, USA. · J Urol. · Pubmed #19286210 No free full text.

Abstract: PURPOSE: Nonsteroidal anti-inflammatory drugs such as aspirin prevent cardiovascular disease and several prior studies suggest that nonsteroidal anti-inflammatory drugs also decrease prostate inflammation and prostate cancer risk. We investigated the association between nonsteroidal anti-inflammatory drug use, prostate specific antigen and prostate volume, hypothesizing that there would be lower prostate specific antigen and prostate volume with nonsteroidal anti-inflammatory drug use. MATERIALS AND METHODS: The Nashville Men's Health Study uses a multicenter, rapid recruitment protocol to collect clinical, biological, behavioral and body measurement data on 1,277 men older than 40 years who are scheduled for diagnostic prostate biopsy. Nonsteroidal anti-inflammatory drug use was ascertained by survey and clinical interview. Medical charts were reviewed to ascertain current prostate specific antigen, prostate volume and clinical diagnoses following biopsy. RESULTS: Approximately 46% of patients reported receiving nonsteroidal anti-inflammatory drugs, primarily aspirin (37%). After adjusting for age, race and other factors prostate volume was similar between aspirin users and nonusers (47.6 vs 46.0 ml, p = 0.16). In contrast, prostate specific antigen was significantly lower in aspirin users (7.3 vs 8.0 ng/ml, p = 0.01). The association between prostate specific antigen and aspirin was significant in men with latent prostate cancer (6.1 vs 7.3 ng/ml, p <0.01), marginal in patients with high grade prostatic intraepithelial neoplasia (5.0 vs 5.9 ng/ml, p = 0.09) and nonsignificant in those with a negative biopsy (5.6 vs 5.7 ng/ml, p = 0.64). The strongest prostate specific antigen-aspirin association was in men with cancer and a prostate volume of 60 ml or more (7.3 vs 12.7 ng/ml, p <0.01). CONCLUSIONS: Prostate specific antigen was significantly lower in aspirin users with latent cancer. Prostate volume was not associated with nonsteroidal anti-inflammatory drug use. Results suggest that aspirin may affect prostate cancer detection, suggesting a potential detection bias to address in future studies of nonsteroidal anti-inflammatory drugs and prostate cancer prevention.

Chan RC, Barocas DA, Chang SS, Herrell SD, Clark PE, Baumgartner R, Smith JA, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA. · BJU Int. · Pubmed #18399829 No free full text.

Abstract: OBJECTIVE: To evaluate the outcomes based on gland size between robotically assisted radical prostatectomy (RALP) and open RP (RRP), as larger prostates might increase the difficulty of RP. PATIENTS AND METHODS: We reviewed 660 patients who had RALP and 340 who had RRP from May 2003 to August 2006; the patients were divided into two groups, with a prostate of >75 and <or=75 g. The clinical characteristics, surgical approach, perioperative and postoperative outcomes were evaluated. RESULTS: Patients with large prostates were significantly older (P < 0.001), but had a lower pathological stage (RALP, P = 0.046, and RRP, P = 0.008) than patients with small glands, regardless of technique. There was no difference in length of stay or transfusion rates between the groups. A large prostate increased the operative duration of RALP (P < 0.001) but not of RRP. For both RALP and RRP, positive margin rates were lower with larger glands (RALP, P = 0.014; RRP, P = 0.033). Overall, the positive margin rates were lower with RALP (9.9% and 19.0%) than RRP (18.5% and 35.5%) among patients with larger or smaller (P < 0.001) glands, respectively. CONCLUSIONS: Prostates of >or=75 g had fewer positive margins than smaller glands, regardless of surgical technique. There was also a significant decrease in positive margin rate in among prostates of >75 g in favour of RALP. Thus, RALP appears to be comparable with RRP for patients with large glands, and might reduce the positive margin rate.

Fowke JH, Matthews CM, Buchowski MS, Signorello LB, Chang SS, Cookson MS, Blot WJ. · Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN 37203-1738, USA. · Prostate Cancer Prostatic Dis. · Pubmed #17938644 No free full text.

Abstract: Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n=121) and Caucasian (CA) (n=121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA=0.99, 0.93, 0.75 and 0.53 ng ml(-1) across quartiles of C-peptide, respectively; P(trend)=0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA=0.84, 0.73, 0.77 and 0.45 ng ml(-1) across quartiles of HbA1c, respectively; P(trend)=0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.

Smith JA, Chan RC, Chang SS, Herrell SD, Clark PE, Baumgartner R, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · J Urol. · Pubmed #17936849 No free full text.

Abstract: PURPOSE: Surgical technique, patient characteristics and method of pathological review may influence surgical margin status. We evaluated the incidence and location of positive surgical margins in 200 sequential robotic assisted laparoscopic radical prostatectomy and 200 sequential open radical retropubic prostatectomy cases. MATERIALS AND METHODS: From July 2002 until December 2006 a total of 1,747 patients underwent radical prostatectomy at our institution (robotic assisted laparoscopic radical prostatectomy in 1,238, radical retropubic prostatectomy in 509). From these we selected the last 200 consecutive radical retropubic prostatectomies and 200 robotic assisted laparoscopic radical prostatectomies performed before August 2006. Preoperative clinical characteristics including age, clinical stage, prostate specific antigen and Gleason score were evaluated. Postoperatively pathological specimens were assessed for specimen weight, Gleason score, tumor volume, pathological stage and margin status. The incidence and location of positive surgical margins were compared between robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy. RESULTS: Patients undergoing robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy had more favorable tumor characteristics including lower prostate specific antigen, clinical stage and Gleason score. No statistically significant differences were found between groups for prostate volume or tumor volume. However, tumor volume as a percentage of prostate volume was higher among radical retropubic prostatectomy compared to robotic assisted laparoscopic radical prostatectomy cases (17.7% vs 13%, p = 0.001). The overall incidence of positive surgical margins was significantly lower among the robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy cases (15% vs 35%, p <0.001). The incidence of positive surgical margins according to pathological stage for robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy cases was 16 of 171 (9.4%) vs 33 of 137 (24.1%) for pT2 (p <0.001) and 14 of 28 (50%) vs 36 of 60 (60%) for pT3. In both groups the apex was the most common site of positive surgical margins with 52% in the robotic assisted laparoscopic radical prostatectomy group vs 37% in the radical retropubic prostatectomy group (p >0.05). CONCLUSIONS: In the hands of surgeons experienced in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy, there was a statistically significant lower positive margin rate for patients undergoing robotic assisted laparoscopic radical prostatectomy. The most common location of a positive surgical margin in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy cases was at the apex. Patients treated with radical retropubic prostatectomy had higher risk features which may have independently influenced these results. The method of pathological specimen analysis and reporting may account for the higher positive margin rates in both groups compared to some reports.

Fleshner N, Gomella LG, Cookson MS, Finelli A, Evans A, Taneja SS, Lucia MS, Wolford E, Somerville MC, Rittmaster R, Anonymous00051. · University Health Network, Princess Margaret Hospital, Toronto, ON, Canada. · Contemp Clin Trials. · Pubmed #17573244 No free full text.

Abstract: PURPOSE: Men with prostate cancer may live as long as men their age without prostate cancer. Those with low-risk disease may benefit from expectant management, which actively monitors disease progression. Dutasteride, a dual 5alpha-reductase inhibitor (5ARI), may delay prostate cancer progression or extend the time to initiation of more aggressive therapy. MATERIALS AND METHODS: The Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial will evaluate whether dutasteride decreases time to prostate cancer progression. Three hundred candidates for expectant management with biopsy-proven, low-risk, localized prostate cancer will receive dutasteride 0.5 mg/day or placebo for 3 years. Eligible men are between 50 and 80 years of age, have clinical stage T1c-T2a prostate cancer, a Gleason score of less than or equal to 6, and serum prostate-specific antigen (PSA) less than or equal to 10 ng/mL. Entry biopsy of at least 10 cores had to be performed within 6 months of screening and will be repeated at 1.5 and 3 years. Men will complete questionnaires to measure symptoms, quality of life (QOL), and anxiety. Because PSA is an important monitoring tool in expectant management that may impact patients' comfort levels, actual PSA values will be provided to physicians and subjects. Time-to-disease progression (primary therapy for prostate cancer or pathologic progression), positive cores, change in Gleason score, and QOL assessments will be compared between groups. RESULTS: The trial completed recruitment of 302 subjects in March 2007. The study will be completed in 2010. CONCLUSIONS: The REDEEM study will evaluate the potential for dutasteride to delay disease progression in men with low-risk, localized prostate cancer. This study will better define which patients with prostate cancer can be managed with less invasive and potentially less debilitating therapy.

Fowke JH, Motley SS, Wills M, Cookson MS, Concepcion RS, Eckstein CW, Chang SS, Smith JA. · Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, 1215 21St Ave. South, Nashville, TN 37232-8300, USA. · Cancer Causes Control. · Pubmed #17334811 No free full text.

Abstract: The relationship between obesity and prostate cancer remains unclear. We investigated the effect of prostate volume on the obesity and prostate cancer association. With a multi-centered, rapid-recruitment protocol, weight and body size measurements were collected prior to diagnosis, and medical charts were reviewed for pathology results (n = 420 controls, 119 high-grade prostatic intraepithelial neoplasia (PIN) cases, and 286 cancer cases (41% Gleason > 6). In multivariable logistic regression models adjusting for age, PSA levels and history, DRE results, and number of cores at biopsy, the association between BMI and cancer was restricted to men with a smaller prostate volume (volume < 40 cm(3): OR(BMI > or = 30) = 2.17 (1.09, 4.32), p (trend) = 0.02; volume > or = 40 cm(3): OR(BMI > or = 30) = 0.77 (0.34, 1.77), p (trend) = 0.17; p (interaction) = 0.03). Similarly, the WHR and PIN association was significantly modified by prostate volume (volume < 40 cm(3): OR((WHR: Tertile 3 vs. T1)) = 3.76 (1.54, 9.21) (p (trend) < 0.01); volume > or = 40 m(3): OR((WHR: T3 vs. T1)) = 0.63 (0.32, 1.23) (p (trend) = 0.17); p (interaction) < 0.01). In conclusion, prostate volume acts as a modifier, and BMI and WHR are significantly associated with prostate cancer or PIN, respectively, in the absence of biopsy sampling error derived from obesity-related prostate enlargement.

Nelson B, Kaufman M, Broughton G, Cookson MS, Chang SS, Herrell SD, Baumgartner RG, Smith JA. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · J Urol. · Pubmed #17296378 No free full text.

Abstract: PURPOSE: Minimally invasive surgery has been shown to decrease postoperative morbidity and length of stay for a number of surgical procedures. Furthermore, length of stay after open radical prostatectomy has decreased dramatically during the last decade. We examined differences in length of stay between a prospectively evaluated cohort of patients who underwent radical retropubic prostatectomy and robot assisted laparoscopic prostatectomy. MATERIALS AND METHODS: Between January 2003 and March 2006, 1,003 radical prostatectomies were performed at our hospital. Data were collected in prospective fashion and a comparison was made between 374 patients who underwent radical retropubic prostatectomy and 629 who underwent robot assisted laparoscopic prostatectomy. Length of stay, factors influencing length of stay, readmission rates and unscheduled clinic or emergency room visits were evaluated. Patients in the 2 groups were treated using the same clinical care pathway. RESULTS: Overall 94.3% of patients in the radical retropubic prostatectomy group and 97.5% in the robot assisted laparoscopic prostatectomy group were discharged home on or before postoperative day 1. Mean length of stay in the radical retropubic and robot assisted laparoscopic prostatectomy groups was 1.25 (median 1.09) and 1.17 days (median 1.03), which was similar and not statistically different (p=0.27). Readmission rates were similar in robot assisted laparoscopic and radical retropubic prostatectomy patients (7% and 5%, respectively, p=0.12). Unscheduled clinic or emergency room visits were the same in the robot assisted laparoscopic and radical retropubic prostatectomy groups (10%, p=0.95). CONCLUSIONS: Patients who underwent radical retropubic prostatectomy or robot assisted laparoscopic prostatectomy can be treated on the same clinical pathway. A targeted hospital discharge date of postoperative day 1 can be achieved in the majority of patients who underwent radical prostatectomy. Readmission rates or unscheduled hospital visits are necessary in a small percent of patients treated with an early discharge program, of which the majority are caused by ileus.

Jung C, Cookson MS, Chang SS, Smith JA, Dietrich MS, Teng M. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. · BJU Int. · Pubmed #17155969 No free full text.

Abstract: OBJECTIVE: To assess gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated with salvage radiotherapy (SRT) at doses of 70.2 Gy after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: Medical records were reviewed retrospectively to identify patients treated with SRT after RRP between January 1999 and December 2005. Of the 62 patients identified, 30 were included for analysis. GI and GU toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and the American Urological Association Symptom Index (AUASI), respectively. RESULTS: The median AUASI score of the 17 patients with scores before SRT was 4, of the 24 with scores after SRT was 6, and of the 15 with scores before and after SRT the median increase was 3. Of the 29 patients with GI toxicity data, nine (31%) had diarrhoea after SRT (three after <70.2 Gy and six after 70.2 Gy). In all cases, the diarrhoea was mild (grade 1). Of all patients, 12 (41%) had proctitis after SRT (four after <70.2 Gy and eight after 70.2 Gy); the proctitis was grade 1 in four and grade 2 in eight, with no cases of grade 3 proctitis. There was no statistically significant difference in the median change in AUASI scores and GI toxicity incidence between patients receiving <70.2 or 70.2 Gy of SRT. CONCLUSION: High-dose SRT (70.2 Gy) is generally well tolerated with acceptable low-grade GI toxicity and minimal changes in AUASI scores.

Hassan JM, Cookson MS, Smith JA, Chang SS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA. · J Urol. · Pubmed #16697802 No free full text.

Abstract: PURPOSE: We characterized initial relapse patterns in patients who underwent cystectomy for transitional cell carcinoma of the bladder at our institution. MATERIALS AND METHODS: Between June 1995 and December 2001 a total of 417 patients underwent radical cystectomy for transitional cell carcinoma. Of the 399 patients treated with orthotopic diversion or incontinent cutaneous diversion, recurrent TCC developed in 86 (21.6%). We retrospectively examined this population to determine if any perioperative variables influenced the first site of disease recurrence. RESULTS: Of the 86 patients in whom metastatic disease developed after cystectomy, the mean followup was 22.1 months. Mean time to disease recurrence was 15.1 months. Recurrence was most commonly initially in the pelvis (30.2%). Other common sites of first recurrence included the viscera (26.7%), the retroperitoneum (16.3%) and the skeletal system (16.3%). The site of first recurrence did not correlate significantly with gender, age, diversion type, pathological stage, nodal status, prostatic involvement or the presence of a positive surgical margin. Lymphovascular invasion was more prevalent in the pelvic recurrence group (62%) than in the retroperitoneal (36%), visceral (22%) or skeletal metastases (29%) groups (p = 0.03). CONCLUSIONS: While the pelvis is the most common site of disease recurrence following radical cystectomy, TCC of the bladder recurs in an unpredictable pattern and aggressive surveillance is indicated. Patients with local pelvic recurrence had a higher percentage of lymphovascular invasion on cystectomy than the other recurrence site groups.

Nelson BA, Shappell SB, Chang SS, Wells N, Farnham SB, Smith JA, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA. · BJU Int. · Pubmed #16686706 No free full text.

Abstract: Authors from the USA sought to establish the relationship between tumour volume, pathological stage and outcomes after radical prostatectomy. In a large series of patients they found that tumour volume was correlated directly with pathological stage, and that it was independently correlated with PSA recurrence. The authors suggested that tumour volume had a potential use for prognostication in patients undergoing radical prostatectomy. Two papers, one from the USA and one from Germany, advise a re-staging TUR in patients with superficial bladder cancer who are at high risk of early tumour progression. In a large series of patients they found that residual tumour after initial resection was commoner than might be expected, and that the second resection indicated the way to earlier radical treatment and a better prognosis. OBJECTIVE: To establish the relationship between tumour volume (TV), pathological stage and outcome after radical prostatectomy (RP), as TV is theoretically an important variable in prostate cancer pathology, but to date it has not been routinely reported and its independent prognostic significance is not well defined. PATIENTS AND METHODS: The study included 431 consecutive patients undergoing RP for clinically localized cancer, from January 2000 to January 2002, who had a pathological examination of totally submitted whole-mount processed RP specimens. In addition to Gleason grade, tumour stage and margin assessment by standard techniques, TV was determined by digital planimetry. The total TV or index TV, for cases with obvious discrete separate tumours, were correlated with pathological stage and prostate-specific antigen (PSA) recurrence. RESULTS: The mean (range) follow-up was 25.4 (6-51) months, and the mean TV for all patients was 3.28 (0.4-38.8) mL. There was a direct correlation between TV and pathological stage (P < 0.001). The TV for organ-confined and extraprostatic disease was 2.09 and 6.02 mL, respectively (P < 0.001). In a multivariate analysis, TV was an independent predictor of PSA recurrence (P = 0.04). The mean TV for patients with PSA recurrence vs no recurrence was 6.8 and 2.6 mL, respectively (P < 0.001). CONCLUSION: TV correlates directly with pathological stage in RP specimens; furthermore, it is independently correlated with PSA recurrence. TV has potential use for prognostication in patients undergoing RP, and may be combined with other well established clinical variables to aid in predicting outcomes.

Pitkänen-Arsiola T, Tillman JE, Gu G, Yuan J, Roberts RL, Wantroba M, Coetzee GA, Cookson MS, Kasper S. · Institute of Applied Biotechnology, University of Kuopio, Kuopio, Finland. · Prostate. · Pubmed #16652386 No free full text.

Abstract: BACKGROUND: Mechanisms regulating the transition from hormone responsive to hormone refractory prostate cancer (PCa) have remained unclear. METHODS: We analyzed androgen and anti-androgen treatment on endogenous AR activity in primary human prostate epithelial (HPE) cells cultured directly from patient radical prostatectomy specimens utilizing a transiently infected gene reporter (TIGR) assay. RESULTS: Flutamide treatment exhibited agonist activities in HPE cells derived from tumor and non-tumor specimens which contained wild-type AR. After proteomic comparison of these cells to those where flutamide functioned normally as an antagonist, we identified DJ-1, a positive regulator of AR. DJ-1 expression increased in HPE and LNCaP cells during flutamide treatment as a result of DJ-1 protein stabilization. CONCLUSION: Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.

Girasole CR, Cookson MS, Putzi MJ, Chang SS, Smith JA, Wells N, Oppenheimer JR, Shappell SB. · OUR Lab and Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. · J Urol. · Pubmed #16469583 No free full text.

Abstract: PURPOSE: We reviewed our results from a urological pathology reference laboratory with respect to the incidence of HGPIN, and atypical and suspicious lesions in the spectrum of ASAP. Subsequent CaP findings on repeat biopsy with relevant clinical implications were assessed. MATERIALS AND METHODS: A review of 42,667 prostate biopsies was performed. We defined atypical and suspicious as variants of ASAP with suspicious being more worrisome for CaP. Findings were correlated with the location of CaP on repeat prostate biopsy. RESULTS: The rate of subsequent CaP detection was significantly higher for an initial diagnosis of suspicious findings (51% or 54 of 107 cases) than for atypical findings (34% or 39 of 116) or HGPIN (22% or 79 of 358, p < 0.001). CaP was found on the same side of the prostate in 61 of 78 (78%), 30 of 39 (77%) and 41 of 54 patients (76%) with initial HGPIN, atypical and suspicious biopsies, respectively. There was no significant difference among the 3 groups in the likelihood of future CaP at the same site or the same side of the prostate. CONCLUSIONS: Patients with a suspicious biopsy were significantly more likely to have CaP on future biopsy than those with atypical findings or HGPIN, suggesting that there may be divisions with prognostic significance in the larger category of ASAP. To our knowledge the reproducibility of recognizing such divisions remains to be established. Neither atypical nor suspicious lesions were more likely than HGPIN to predict CaP at the same site or side of the prostate as the original diagnosis. Repeat biopsy may be indicated in any patient with HGPIN, or atypical or suspicious lesions and this biopsy should not be limited to the site or side of the original pathological findings.

Kaufman MR, Smith JA, Baumgartner RG, Wells N, Chang SS, Herrell SD, Cookson MS. · Department of Urologic Surgery, Vanderbilt University, Nashville, TN, USA. · BJU Int. · Pubmed #16469010 No free full text.

Abstract: OBJECTIVE: To define changes in the clinical pathway for open radical retropubic prostatectomy (RRP) and to determine their impact on patient care under the indirect influence of minimally invasive prostatectomy after implementing robotically assisted laparoscopic prostatectomy (RALP) at our institution and modifying the collaborative-care pathway. PATIENTS AND METHODS: We retrospectively reviewed the Vanderbilt Prostate Database since the initiation of RALP in May 2003, evaluating those patients who had open RRP. Data were analysed in three consecutive 5-month blocks to determine incremental changes in protocol and outcomes, including complications and re-admissions. RESULTS: Between May 2003 and August 2004, 196 patients had RALP and 183 had RRP. After May 2003, there was a progressive reduction for open RRP in the length of stay from 1.6 to 1.3 days. Analysis also showed an elimination of patient-controlled analgesia, a rapid diet advancement, and drain removal at the surgeon's discretion. There were no major complications after surgery, and three minor complications (1.6%). The rate of re-admission after open RRP was low throughout the study period (seven patients, 3.8%), and did not increase progressively. CONCLUSIONS: The management after open RRP was modified substantially after implementing RALP, with the two clinical pathways now similar. Despite these modifications in the treatment of patients having open RRP there was no increase in morbidity or compromise in patient outcome. Indeed, this study shows the feasibility and safety of a 1-day length of stay for open RRP.

Chang SS, Cole E, Smith JA, Baumgartner R, Wells N, Cookson MS. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. · Cancer. · Pubmed #15999365 links to  free full text

Abstract: BACKGROUND: Collaborative care pathways have proven to be a safe and effective method of decreasing length of hospital stay (LOS) and costs after radical retropubic prostatectomy (RRP). In the current study, the authors evaluated the safety and efficacy of a pathway transitioning from a 3-day to a 2-day LOS. METHODS: The authors performed a retrospective chart review of 994 patients who underwent RRP at the study institution between July 1994 and December 2001. A total of 561 patients were managed on a 3-day LOS pathway, 172 were managed during the transition period from 3 to 2 days, and 261 were managed on a 2-day LOS pathway. Statistical analysis was performed comparing preoperative variables and complications among the three groups. RESULTS: No statistically significant differences were found in comparisons of preoperative and demographic variables including age, race, medical comorbidities, preoperative prostate-specific antigen level, clinical stage of disease at presentation, and biopsy Gleason score. Forty-nine of the 561 patients (8.7%) remained longer than their targeted 3-day LOS, whereas 14 of 261 patients (5.4%) were hospitalized for longer than their targeted 2-day LOS, a difference that approached statistical significance (P = 0.058). During the transition period, 99 of 172 patients (57.6%) were discharged on postoperative Day 2 and 73 patients (42.4%) were discharged on postoperative Day 3. Complication rates were found to be significantly lower (P = 0.013) in the 2-day LOS group (2.3%) compared with the 3-day LOS group (7.0%) and the transition group (8.1%). The rate of readmission remained constant at 3% during this time period. CONCLUSIONS: Overall, greater than 90% of patients were discharged within 2-3 days of surgery with acceptable complication rates, suggesting that in a consistent patient population, the transition from a 3-day LOS to a 2-day LOS can be done successfully without compromising patient safety. Evaluation currently is ongoing with regard to a 1-day LOS.