The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series.

OBJECTIVE: To analyze the association of diabetes mellitus (DM) with risk of prostate cancer and cancer grade among men undergoing prostate biopsy and to analyze how obesity and race modify these associations. MATERIALS AND METHODS: Retrospective analysis of 998 men from the Durham VA undergoing first prostate biopsy between 2001 and 2009 with complete data available. History of DM was determined by chart review. Patients' characteristics at biopsy were analyzed with chi-square and ranksum. Multivariable analyses of DM and risk of cancer and cancer grade were done using logistic regression adjusting for PSA, body mass index, race, age, year, and digital rectal exam. RESULTS: At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p < 0.001). DM was not associated with prostate cancer risk on either bivariate (p = 0.600) or multivariate analysis (p = 0.485). Similar results were found after stratification by race and obesity. In multivariable analysis, DM was associated with greater risk of high-grade disease (RR = 2.13, p = 0.024). The association was stronger among obese men (RR = 3.84, p = 0.020) and null in non-obese subjects (RR = 1.39, p = 0.460). After further stratification by race, DM was associated with high-grade disease only in obese Caucasian men (CM; RR = 5.81, p = 0.025) but not in obese AAM. DM was not associated with risk of low-grade disease in all men together or after stratification by obesity or race. CONCLUSION: History of DM was associated with greater risk of high-grade disease. The association was strongest among obese CM suggesting the effect of DM on high-grade prostate cancer is modified by race and obesity.

Association between statins and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy.

BACKGROUND: Cholesterol-lowering drugs known as statins have been reported to have significant anti-inflammatory properties. Given that inflammation may contribute to prostate cancer progression and that statins may reduce the risk for advanced prostate cancer, we investigated whether statin use was associated with reduced intratumoral inflammation in radical prostatectomy (RP) specimens. METHODS: Inflammation within index tumors of 236 men undergoing RP from 1996 to 2004 was graded by a single pathologist as grade 0 (absent), 1 (mild: < or =10%), and 2 (marked: >10%). Preoperative statin use was analyzed by grouping subjects as statin users or nonusers. Type and dosage of statin was accounted for using dose equivalents with 20 mg simvastatin as reference. Logistic regression was used to determine the association between statin use and intratumoral inflammation controlling for age, race, body mass index, prostate-specific antigen, year of surgery, clinical stage, pathologic Gleason sum, surgical margin status, extracapsular extension, seminal vesicle invasion, prostate weight, time from prostate biopsy to RP, and nonsteroidal anti-inflammatory drug use. RESULTS: Preoperative statin use was significantly associated with lower risk for any (grade > or =1) intratumoral inflammation (odds ratio, 0.31; 95% confidence interval, 0.10-0.98; P = 0.047) on multivariable analysis, with doses > or =20 mg simvastatin equivalents being more strongly associated (relative to nonuse; odds ratio, 0.22; 95% confidence interval, 0.06-0.79; P = 0.02). CONCLUSION: In a cohort of men undergoing RP, statin use was associated with significantly lower risk of any inflammation within prostate tumors. IMPACT: Given previous reports that inflammation is associated with advanced prostate cancer, and statin use is associated with decreased prostate cancer progression risk, our findings suggest that inhibition of inflammation within tumors may be a potential mechanism for purported anti-prostate cancer properties of statins.

Diabetes and outcomes after radical prostatectomy: are results affected by obesity and race? Results from the shared equal-access regional cancer hospital database.

BACKGROUND: Diabetes is associated with lower prostate cancer risk. The association of diabetes with prostate cancer outcomes is less clear. We examined the association between diabetes and outcomes after radical prostatectomy and tested whether associations varied by race and/or obesity. MATERIALS AND METHODS: This study is a retrospective analysis of 1,262 men treated with radical prostatectomy between 1988 and 2008 within the Shared Equal-Access Regional Cancer Hospital database. We examined the multivariate association between diabetes at surgery and adverse pathology, biochemical recurrence (BCR), and prostate-specific antigen doubling time at recurrence using logistic, proportional hazards, and linear regression, respectively. Data were examined as a whole and stratified by race and obesity. RESULTS: Diabetes was more prevalent among black (22% versus 15%, P < 0.001) and more obese men (P < 0.001). Diabetes was associated with higher tumor grade (odds ratio, 1.73; P = 0.002), seminal vesicle invasion (odds ratio, 1.73; P = 0.04), but not BCR (P = 0.67) or PSADT at recurrence (P = 0.12). In the secondary analysis, among white obese men, diabetes was associated with 2.5-fold increased BCR risk (P = 0.002) and a trend toward shorter PSADT, whereas among all other men (nonobese white men and black men), diabetes was associated with 23% lower recurrence risk (P = 0.09) and longer PSADT (P = 0.04). CONCLUSION: In a radical prostatectomy cohort, diabetes was not associated with BCR. In the secondary analysis, diabetes was associated with more aggressive disease in obese white men and less aggressive disease for all other subsets. If externally validated, these findings suggest that among men with prostate cancer, the association between diabetes and prostate cancer aggressiveness may vary by race and obesity.

The Shared Equal Access Regional Cancer Hospital (SEARCH) nomogram for risk stratification in intermediate risk group of men with prostate cancer: validation in the Duke Prostate Center database.

OBJECTIVES: To validate the Shared Equal Access Regional Cancer Hospital (SEARCH) nomogram to better risk stratify men with intermediate-risk pathology after prostatectomy (positive surgical margins, PSM, and/or extracapsular disease, ECE, without seminal vesicle or lymph node involvement) in a tertiary referral centre (the Duke Prostate Center, DPC). PATIENTS AND METHODS: We retrospectively analysed 485 men in the DPC cohort with PSM and/or ECE but without seminal vesicle or lymph node involvement. The predicted risk of biochemical progression-free probability at 1, 3 and 5 years was estimated by the SEARCH and updated Kattan postoperative nomograms. Calibration plots were generated and accuracy assessed with the concordance index. RESULTS: The SEARCH nomogram appeared to be well calibrated, with the highest-risk quartile having a predicted <60% progression-free probability at 5 years, vs >80% for the lowest risk. In comparison, overall external calibration appeared to be similar for the updated Kattan nomogram, although there was less separation between the highest- and lowest-risk quartiles. The SEARCH model had an overall predictive accuracy of 0.65, which compared favourably with the updated Kattan nomogram (0.57). CONCLUSION: In an external dataset, the SEARCH nomogram to predict progression-free probability for men at intermediate risk after prostatectomy was well calibrated and performed better than the updated postoperative Kattan nomogram.

Obesity as a predictor of adverse outcome across black and white race: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database.

BACKGROUND: Across multiple studies, obesity has been associated with an increased risk of higher grade disease and prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Whether these associations vary by race is unknown. In the current study, the authors examined the association between obesity and outcome after RP stratified by race. METHODS: A retrospective analysis was performed on 1415 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1989 and 2008. The association between increased body mass index (BMI) and adverse pathology and biochemical recurrence was examined using multivariate logistic regression and Cox models, respectively. Data were examined stratified by race. RESULTS: After adjusting for preoperative clinical characteristics, higher BMI was associated with higher tumor grade (P = .008) and positive surgical margins (P < .001) in white men, and similar but statistically nonsignificant trends were observed in black men. No significant interaction was noted between race and BMI for associations with adverse pathology (P(interaction)> or =.12). After adjusting for preoperative clinical characteristics, higher BMI was associated with an increased risk of recurrence in both white men (P = .001) and black men (P = .03). After further adjusting for pathologic variables, higher BMI was associated with significantly increased risk of recurrence in white men (P = .002) and black men (P = .01). No significant interactions were observed between race and BMI for predicting biochemical progression adjusting either for preoperative factors (P(interaction) = .35) or for preoperative and pathologic features (P(interaction) = .47). CONCLUSIONS: Obesity was associated with a greater risk of recurrence among both black men and white men. Obesity did not appear to be more or less influential in 1 race than another but, rather, was identified as a risk factor for aggressive cancer regardless of race.

Validation of a nomogram to predict disease progression following salvage radiotherapy after radical prostatectomy: results from the SEARCH database.

OBJECTIVE: To externally validate the nomogram published by Stephenson et al. (termed the 'Stephenson nomogram') to predict disease progression after salvage radiotherapy (SRT) among patients with prostate cancer from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. PATIENTS AND METHODS: We analysed data from 102 men treated with SRT for prostate-specific antigen (PSA) failure after prostatectomy, of whom 30 (29%) developed disease progression after SRT during a median follow-up of 50 months. The predicted 6-year progression-free survival (PFS) was compared to the actuarial PFS using calibration plots. The accuracy of the nomogram to risk-stratify men for progression was assessed by the concordance index. RESULTS: The median PSA and PSA doubling time before SRT was 0.6 ng/mL and 10.3 months, respectively. The 6-year actuarial disease-free progression after SRT was 57% (95% confidence interval 42-69%). The overall concordance index of the Stephenson nomogram was 0.65. The nomogram predicted failure more accurately at the extremes of risk (lowest and highest) but in intermediate groups, the accuracy was less precise. Of the 11 variables used in the nomogram, only negative margins and high PSA level before SRT were significantly associated with increased disease progression. CONCLUSION: The Stephenson nomogram is an important tool to predict disease progression after SRT following radical prostatectomy. It adequately predicted progression in SEARCH with reasonable accuracy. Also, in SEARCH, disease progression was predicted by similar disease characteristics. However, the overall modest performance of the model in our validation cohort indicates there is still room for improvement in predictive models for disease progression after SRT.

Factors predicting prostatic biopsy Gleason sum under grading.

PURPOSE: We determined clinical factors affecting the under grading of biopsy Gleason sum compared with prostatectomy pathology and developed a model predicting the probability of under grading. MATERIALS AND METHODS: We analyzed a cohort of 1,701 patients treated for prostate cancer at our institution between 1988 and 2007 with complete biopsy and pathological data available. Patients with a biopsy Gleason sum of 7 or less were included in our analysis. Cases were categorized as under graded or not under graded by comparing biopsy and radical prostatectomy Gleason sums. Logistic regression was used to determine the predictors of under grading based on clinical variables (race, age at diagnosis, body mass index, prostate weight, diagnostic prostate specific antigen, biopsy positive-to-total core ratio, maximal cancer percent in positive cores and time from diagnosis to surgery). A nomogram was developed to calculate the probability of under grading. Results were validated using bootstrapping. RESULTS: Under grading occurred in 46.6% of our cohort. Significant variables predicting under grading were age at diagnosis, biopsy Gleason sum, diagnostic prostate specific antigen, prostate weight, biopsy positive-to-total core ratio and maximal percent of cancer in cores (p <0.05). Nomogram predictive accuracy was 72.4%. CONCLUSIONS: The risk of Gleason sum under grading can be predicted to a satisfactory level using our nomogram. Predicting under grading would improve patient consulting and identify those who should consider repeat biopsy, ultimately enhancing the accuracy of prostate cancer diagnosis.

Obesity and positive surgical margins by anatomic location after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database.

OBJECTIVES: To determine if there is predilection for any specific anatomical location of positive surgical margins (PSMs) after radical prostatectomy (RP) for prostate cancer in obese men, as previous studies found that obesity was associated with an increased risk of PSMs. PATIENTS AND METHODS: We analysed retrospectively 1434 men treated with RP between 1989 and 2007 within the Shared Equal Access Regional Cancer Hospital database. The association between increased body mass index (BMI) and overall and site-specific PSMs was assessed using multivariate logistic regression. RESULTS: After adjusting for several preoperative clinical and pathological characteristics, a higher BMI was associated with an increased risk of PSMs both overall and at all specific anatomical locations (all P or=35 kg/m2, there was more variation, with the highest excess risk of PSMs at the bladder neck and apex. CONCLUSIONS: Obesity was associated with an increased risk of overall PSMs and at all anatomical locations. Although the excess risk of PSMs was similar across all anatomical locations, there was a suggestion of a higher risk of apical margins among the most obese men, which if validated, further supports the importance of the apical dissection in all men and suggests added difficulty in obese patients.

Risk stratification for biochemical recurrence in men with positive surgical margins or extracapsular disease after radical prostatectomy: results from the SEARCH database.

PURPOSE: In men with extracapsular disease or positive surgical margins after radical prostatectomy immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We further stratified these men into a low risk group in which watchful waiting after surgery may be preferred and a high risk cohort in which adjuvant therapy may be preferred. MATERIALS AND METHODS: We performed a retrospective analysis of the records of 902 men treated with radical prostatectomy in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database between 1988 and 2007 with positive surgical margins and/or extracapsular disease without seminal vesicle invasion or lymph node metastasis. The significant independent predictors of biochemical recurrence were determined using a multivariate Cox proportional hazards model. Based on the recurrence risk generated from the multivariate Cox proportional hazards regression model we generated tables to estimate the risk of recurrence-free survival 1, 3 and 5 years after surgery. RESULTS: At a median of 3 years of followup 346 patients (39%) had biochemical recurrence. On multivariate analysis the significant predictors of biochemical recurrence were age more than 60 years, prostate specific antigen more than 10 ng/ml, Gleason score 4 + 3 and 8-10, 2 or more sites of positive surgical margins and prostate specimen weight 30 gm or less. As determined by the concordance index, the overall predictive accuracy of the model was 0.67, while it was 0.60 for the postoperative Kattan nomogram in this patient population. CONCLUSIONS: We have developed a simple instrument that, once validated, may aid in the postoperative decision making process for men at intermediate risk for recurrence after prostatectomy.

Prevention of prostate cancer: what we know and where we are going.

As one of the most prevalent cancers, prostate cancer has enormous public health importance and its prevention seems to be a rational approach to attenuate the economic, emotional, physical, and social impact of this disease. This review discusses some of the options available to clinicians worldwide under the broad headings of chemoprevention and dietary modification including lifestyle issues. From the review of available literature, it is appreciated that although many exciting options such as androgen inhibitors, vitamin E, and selenium are being actively considered, they are far from being included in clinical practice. So until large randomized trials confirm the benefit of chemopreventives and dietary modifications, patients may be advised to pursue a diet and lifestyle that ensures overall fitness.