Stephen G. Williams

Use of statins and prostate cancer recurrence among patients treated with radical prostatectomy.

Statins have shown broad spectrum anti‐cancer properties in laboratory studies. In epidemiological studies, use of statins has been associated with reduced risk of advanced prostate cancer. However, the effects of statins on prostate cancer disease progression following curative treatment have not been extensively studied, and previous studies reported conflicting results. This study found no clear association between overall statin use and risk of disease progression, as well as lack of a monotone dose–response relationship between the use of statins, whether it was use before or after prostatectomy, and prostate cancer disease progression.

Impact of Robotic Training on Surgical and Pathologic Outcomes During Robot-assisted Laparoscopic Radical Prostatectomy

OBJECTIVES To prospectively compare outcomes during robotic prostatectomy between surgeons with formal training in either robotic prostatectomy (RALP) or laparoscopic prostatectomy (LRP). METHODS A total of 286 robotic prostatectomies were performed by 12 urologists between August 2008 and March 2009 as part of a new robotic surgery program at one of the largest health maintenance organizations in the United States. Four surgeons had formal training in RALP and 8 had formal training in LRP. We prospectively compared surgical and pathologic outcomes between these 2 groups of surgeons. RESULTS The 4 RALP surgeons performed 121 RALPs and the 8 LRP surgeons performed 165 RALPs. Patient demographics were similar between groups. The robot-naive group had significantly more clinical stage T1c than the robot-trained group (87.9% vs 74.4%, P = .003). Prostatectomy parameters were similar between the 2 groups of surgeons in terms of prostate size, Gleason score, pathologic stage, and estimated blood loss. The robot-trained surgeons had significantly lower overall positive margin rates (24% vs 34.6%, P = .05) and lower margin rates in T3 tumors (38.5% vs 61.8%, P = .07), which were approximately statistically significant. There was no difference in margin rates in T2 tumors. The robot-trained surgeons had significantly lower apical margin rates (8.3% vs 21.2%, P = .003) and lateral margin rates (1.7% vs 7.3%, P = .05). The robot-trained surgeons had 10%-15% shorter procedure times. There was no difference in complication rates. CONCLUSIONS Formal RALP training may be beneficial for surgical and pathologic outcomes of RALP compared with formal LRP training during the initial implementation of a new robotics program.

Statin therapy is not associated with prostate cancer recurrence among patients who underwent radiation therapy

We investigated whether statin use is associated with reduced risk of recurrence in prostate cancer patients who undergo radiotherapy. A retrospective cohort of 774 patients from a California health plan was followed for 5 years. Statin use prior to, during and after radiotherapy was not associated with prostate cancer recurrence [hazard ratio=0.99 (0.70-1.39), 0.87 (0.62-1.22) and 0.78 (0.55-1.09), respectively] in multivariable Cox models. No clear dose-response relationship was observed for average daily statin dose or duration of statin use. Our findings do not support a preventive benefit of statins in prostate cancer recurrence after radiotherapy.

PREDICTING PELVIC LYMPH NODE INVOLVEMENT IN CURRENT-ERA PROSTATE CANCER

PURPOSE The Roach formula [2/3 × prostate-specific antigen + (Gleason score--6) × 10], derived in 1993 during the early prostate specific antigen (PSA) screening era, has been used to predict the risk of pelvic lymph node involvement in patients with prostate cancer. In the current era of widespread PSA screening with a shift to earlier disease stages, there is evidence to suggest that the Roach score overestimates risk of nodal metastasis. This study retrospectively reviews the validity of this formula as a prediction tool. METHODS AND MATERIALS We conducted a retrospective institutional review including men with clinical T1c-T3 prostate cancer, with baseline PSA levels and biopsy-obtained Gleason scores who underwent radical prostatectomy with pelvic node dissection from 2001 through 2009 (N = 1,022). The predicted risk of nodal involvement was calculated for each patient using the Roach formula and then compared with actual rates following surgery. RESULTS The study included 1,022 patients; 99.6% had clinical T1c/T2 disease, with a mean of 10.3 lymph nodes surgically evaluated. Overall, 42 patients (4.1%) had nodal metastasis. For every range of scores, the Roach formula overestimates the risk of nodal involvement. Observed nodal positivity was 1%, 6.3%, 10%, 15.2%, and 16.7% for Roach scores ≤ 10%, >10%-20%, >20%-30%, >30%-40%, and >40%, respectively. The Roach score overestimates the risk by approximately 4.5-fold in patients with scores ≤ 10%, by 2.5-fold for all scores between 10% and 40%, and by 4-fold for scores >40%. CONCLUSION The Roach formula overpredicts the risk of pelvic nodal involvement in current-era prostate cancer patients undergoing regular PSA screening and with mainly T1c/T2 disease. Contemporary patients are much less likely to have nodal involvement for a given PSA and Gleason score.

Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer.

OBJECTIVES Luteinizing hormone releasing hormone (LHRH) agonist therapy is one of the mainstays of prostate cancer treatment. Three dosing regimens currently exist: calendar-based, intermittent, and a testosterone (T)-based (T-based) regimen. We investigated the differences in development of early castrate resistance rates between these different regimens. METHODS We evaluated 1617 patients with prostate cancer who received LHRH-agonist monotherapy in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006. Patients who had undergone surgery and/or radiation were excluded. Patients were grouped according to their dosing regimen: calendar-based, intermittent dosing, and T-based. Cox proportional hazard-regression analysis was used to estimate the hazards ratio (HR) for treatment failure. RESULTS A total of 692 patients who received an LHRH agonist as primary monotherapy for prostate cancer fit our criteria. Calendar-based dosing was used in 325 patients; 252 received T-based dosing and 115 received intermittent dosing. On multivariate analysis controlling for demographic and prostate cancer-related variables, the T-based dosing group showed a significantly lower relative risk of treatment failure (HR = 0.65, P = .02). The intermittent-dosing group trended toward a lower risk treatment failure (HR = 0.80, P = .3). Among the variables analyzed, only a Gleason score >8 (HR = 2.05, P = .01) and a pretreatment prostate-specific antigen >20 (HR = 2.00, P <.01) were associated with a higher risk of treatment failure. CONCLUSIONS During the time period studied, T-based and intermittent dosing regimen of LHRH agonist had lower rates of early castrate resistance compared with standard calendar dosing, based on measurements for early androgen resistance.

Achieving proficiency with robot-assisted radical prostatectomy: Laparoscopic-trained versus robotics-trained surgeons.

BACKGROUND Initiating a robotics program is complex, in regards to achieving favourable outcomes, effectively utilizing an expensive surgical tool, and granting console privileges to surgeons. We report the implementation of a community-based robotics program among minimally-invasive surgery (MIS) urologists with and without formal robotics training. METHODS From August 2008 to December 2010 at Kaiser Permanente Southern California, 2 groups of urologists performing robot-assisted radical prostatectomy (RARP) were followed since the time of robot acquisition at a single institution. The robotics group included 4 surgeons with formal robotics training and the laparoscopic group with another 4 surgeons who were robot-naïve, but skilled in laparoscopy. The laparoscopic group underwent an initial 7-day mentorship period. Surgical proficiency was measured by various operative and pathological outcome variables. Data were evaluated using comparative statistics and multivariate analysis. RESULTS A total of 420 and 549 RARPs were performed by the robotics and laparoscopic groups, respectively. Operative times were longer in the laparoscopic group (p = 0.002), but estimated blood loss was similar. The robotics group had a significantly better overall positive surgical margin rate of 19.9% compared to the laparoscopic group (27.8%) (p = 0.005). Both groups showed improvements in operative and pathological parameters as they accrued experience, and achieved similar results towards the end of the study. CONCLUSIONS Robot-naïve laparoscopic surgeons may achieve similar outcomes to robotic surgeons relatively early after a graduated mentorship period. This study may apply to a community-based practice in which multiple urologists with varied training backgrounds are granted robot privileges.

Abstract 647: Use of statin and risk of prostate cancer recurrence among patients who received radical prostatectomy

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: HMG-CoA reductase inhibitors (“statins”) have shown broad-spectrum anti-cancer properties in laboratory studies. In epidemiologic studies, statin use has been linked to reduced risk of advanced prostate cancer (PCa). We investigated whether statin use is associated with reduced risk of recurrence in PCa patients who received radical prostatectomy. Methods: All men with incident PCa diagnosed between 2004-2005 who subsequently underwent radical prostatectomy in Kaiser Permanente Southern California (KPSC) health plan were identified using KPSCs accredited cancer registry. Exclusion criteria included 0.2 ng/ml; and (2) clinical disease progression, defined as diagnosis of metastatic disease (identified using ICD-9 codes) or PCa-related death (i.e., PCa as primary cause of death). Information on statin use, demographics, co-morbid conditions, pathoclinical prognostic factors, e.g., stage and Gleason score, and outcomes were obtained from cancer registry and electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariable Cox models, adjusting for known prognostic factors. For post-operative statin exposure, a time-dependent Cox model was used. Results: A total of 1192 men were included; 38% had pre-operative and 55% had post-operative statin use. Neither pre- nor post-operative statin use was associated with risk of any outcome, as there was no evidence of a clear dose-response relationship (Table). Conclusion: These data suggest that despite statins protective effect in developing PCa, statin use may not prevent PCa progression. ![Figure][1] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 647. doi:1538-7445.AM2012-647 [1]: pending:yes