Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study.

BACKGROUND: Systemic opioids are immunosuppressive, which could promote tumour recurrence. We, therefore, test the hypothesis that supplementing general anaesthesia with neuraxial analgesia improves long-term oncological outcomes in patients having radical prostatectomy for adenocarcinoma. METHODS: Patients who had general anaesthesia with neuraxial analgesia (n=1642) were matched 1:1 based on age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease with those who had general anaesthesia only. Medical records were reviewed. Outcomes of interest were systemic cancer progression, recurrence, prostate cancer mortality, and all-cause mortality. Data were analysed using stratified proportional hazards regression, the Kaplan-Meier method, and log-rank tests. The median follow-up was 9 yr. RESULTS: After adjusting for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, general anaesthesia only was associated with increased risk for systemic progression [hazard ratio (HR)=2.81, 95% confidence interval (CI) 1.31-6.05; P=0.008] and higher overall mortality (HR=1.32, 95% CI 1.00-1.74; P=0.047). Although not statistically significant, similar findings were observed for the outcome of prostate cancer deaths (adjusted HR=2.2, 95% CI 0.88-5.60; P=0.091). CONCLUSIONS: This large retrospective analysis suggests a possible beneficial effect of regional anaesthetic techniques on oncological outcomes after prostate surgery for cancer; however, these findings need to be confirmed (or refuted) in randomized trials.

Treatment of M1a/M1b prostate cancer with or without radical prostatectomy at diagnosis.

BACKGROUND: The aim of the study was to evaluate survival and perioperative outcomes of metastatic prostate cancer (mPCa) patients treated with surgery or androgen deprivation treatment (ADT) only. METHODS: We retrospectively selected 47 metastatic PCa patients treated at a single center (Mayo Clinic, Rochester, MN) by two urologists (RJK and EK) between 2007 and 2014. Overall, 31 (66%) underwent radical prostatectomy (RP) with or without adjuvant therapies and 16 (34%) underwent ADT only. Surgical patients were treated by a single surgeon (RJK). Complications and functional outcomes were recorded for surgery group. Cancer-specific mortality (CSM) was analyzed by Kaplan-Meier estimation. Univariable Cox regression analyses were used to test the risk factors associated with CSM in mPCa patients treated with RP. RESULTS: Median age at diagnosis was 61 years. During median follow-up 38.8 months, 12 deaths were recorded. At 5 years, the overall CSM-free survival rate of the whole cohort was 57.9%. When patients were stratified according to the treatment, CSM-free survival rate at 5 years was 62% and 46% for patients who underwent surgery and ADT, respectively (P=0.3). Median length of stay was 3 days, with a 30 days readmission rate of 9.7%. The 30-day all complication rate was 29% (n=9). Specifically, we recorded: 2 lymphoceles (6.5%), 2 wound infection (6.5%), 2 ileus (6.5%), 2 hematoma (6.5%) and 1 anastomosis leak (3.2%). Within 90 days after surgery, 2 (6.5%) and 5 (16.1%) patients needed 1-2 supportive and 3 or more pads, respectively. However, continence was achieved by all treated patients during the follow-up period. CONCLUSIONS: We demonstrated the feasibility of local surgical treatment of primary tumor in mPCa patients. However, in the short term, no survival benefits have been observed for patients treated with surgery when compared with patients treated with ADT only. Further prospective studies are warranted to explore the treatment of M1a/M1b prostate cancer patients.

The association of tumor volume with mortality following radical prostatectomy.

BACKGROUND: Data regarding the prognostic significance of tumor volume (TV) in prostate cancer are conflicting. Herein, we evaluated the association of TV with prostate cancer mortality following radical prostatectomy (RP), and assessed the additive prognostic value of TV to an established predictive model. METHODS: We identified 13,687 patients who underwent RP without preoperative therapy between 1987 and 2009. TV was estimated using the prolate ellipsoid formula. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of TV with mortality. The ability of TV to enhance the performance of an established prognostic model (Mayo Clinic GPSM (Gleason, PSA, seminal vesicle and margin status) score) was assessed using the c-index. RESULTS: Median TV was 1.57 cm(3) (interquartile range (IQR) 0.48-4.19). Increasing TV was associated with significantly higher risks of seminal vesicle invasion (hazard ratio (HR) 1.58; P<0.0001), positive surgical margins (HR 1.28; P<0.0001) and lymph node involvement (HR 1.26; P<0.0001). Median postoperative follow-up was 9.4 years (IQR 5.0-14.5). Patient grouping into quartiles according to TV resulted in a significant stratification of outcome, as the 15-year cancer-specific survival by TV quartile was 99%, 98%, 95% and 88%, respectively (P<0.0001). Moreover, on multivariate analysis, greater TV remained associated with significantly increased risks of systemic progression (HR 1.27; P<0.0001), death from prostate cancer (HR 1.29; P<0.0001) and all-cause mortality (HR 1.05; P<0.0001). Meanwhile, addition of TV to the GPSM score increased the c-index for the model's prediction of prostate cancer mortality from 0.803 to 0.822. CONCLUSIONS: TV is associated with survival following RP, and enhances, although modestly, the performance of an established prediction model. As such, TV warrants continued assessment in risk stratification tools.

Obese men have more advanced and more aggressive prostate cancer at time of surgery than non-obese men after adjusting for screening PSA level and age: results from two independent nested case-control studies.

BACKGROUND: It remains unclear whether the hemodilution effect of body mass index (BMI) on PSA levels translates to inappropriate prostate cancer (PCa) screening in obese men. To address this, we conducted two nested case-control studies within prospective cohorts of men undergoing radical prostatectomy for newly diagnosed PCa. METHODS: We identified 1817 men with BMI 30 kg m(-2) (cases) and 1244 men with BMI <25 kg m(-2) (controls) who underwent surgery to treat PCa at Mayo Clinic in Rochester between 2000 and 2009. Cases and controls were frequency matched on age and PSA level. In a similar manner, we identified 206 cases and 133 controls treated at Mayo Clinic in Florida between 2006 and 2011. We employed logistic regression models to evaluate the association of pathologic features of aggressiveness with obesity status. RESULTS: After adjusting for age and PSA level, we noted that obese men in the Rochester population are more likely to present with Gleason grade 8-10 tumors (OR= 1.50; 95% CI 1.14-1.96; P=0.003) and pT3, pT4, pTxN+ stage disease (OR=1.30; 95% CI 1.05-1.62). We noted a similar association seminal vesicle involvement (OR= 1.41; 95% CI 1.03-1.92; P=0.03). Results from the smaller Florida population supported these same associations but did not achieve conventional statistical significance. CONCLUSIONS: Obese men present with more aggressive PCa tumors compared with non-obese men of similar age and PSA screening values. If confirmed, this would support the need to explore PSA-based screening in obese men to possibly account for a hemodilution effect.

Clinicopathological predictors of systemic progression and prostate cancer mortality in patients with a positive surgical margin at radical prostatectomy.

BACKGROUND: Although a positive surgical margin (PSM) at radical prostatectomy (RRP) has been consistently linked to an increased risk of biochemical recurrence, the impact of margin status on patient survival continues to be debated. We evaluated long-term outcomes of patients with a PSM at RRP and determined predictors of systemic progression (SP) and mortality in these men. METHODS: We reviewed our institutional registry of 16,749 patients who underwent RRP between 1990 and 2008 to identify 2895 patients with a PSM. Median follow-up was 10.6 years. Postoperative survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with SP and death from prostate cancer. RESULTS: A 15-year SP-free and cancer-specific survival was 90 and 93%, respectively. On multivariate analysis, higher tumor volume, increased pathological Gleason score and advanced pathological tumor stage were associated with significantly increased risks of SP and death from prostate cancer, whereas number and location of PSM did not predict mortality. CONCLUSIONS: The risks of SP and prostate cancer death in patients with a PSM remain low on long-term follow-up. Tumor variables are the primary determinants of cancer death. These results should be considered when evaluating patients with a PSM for adjuvant therapy.