Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

BACKGROUND: At the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment. METHODS: We conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk. RESULTS: On crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant. CONCLUSIONS: Overweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM.

Long-term oncological outcomes of apical positive surgical margins at radical prostatectomy in the Shared Equal Access Regional Cancer Hospital cohort.

BACKGROUND: Approximately 29-38% of all positive surgical margins (PSMs) at radical prostatectomy (RP) involve the apex. The prognostic significance of apical PSM remains unclear. We therefore compared the long-term oncologic outcomes of men with apical PSMs to those with negative PSMs, apical and other PSMs, and other PSMs at RP. METHODS: The SEARCH (Shared Equal Access Regional Cancer Hospital) database was used to identify 4031 men with prostate cancer (PCa) managed with RP with complete pathologic grade and stage data. Margin status was categorized as negative, apex only, or other positive. Multivariable Cox regression models adjusted for pathologic stage and grade were developed to test the relationship between margin status and biochemical recurrence (BCR), metastases and PCa death. RESULTS: In the final cohort, 34.3% had PSMs, whereas 65.7% had negative margins. Univariable analysis showed that compared with negative margins, apex-only PSM was associated with BCR (hazard ratio (HR): 1.4 [1.1-1.8]), but not metastases or PCa death, whereas apex and other PSMs were associated with BCR (HR: 3.3 [2.8-4]) and metastases (HR: 1.8 [1.02-3.1]) but not PCa death. Nonapical PSMs were associated with BCR (HR: 2.7 [2.4-3.1]), metastases (1.7 [1.2-2.5)] and PCa death (1.8 [1.05-3]). On multivariable analysis, apex-only, apex and other, and nonapical PSMs were associated with BCR but margin status was not associated with metastases or PCa death. CONCLUSIONS: In a large cohort of men undergoing RP, those with PSMs at the prostatic apex had lower BCR, metastases, or PCa death compared with those with PSMs at other locations. When adjusted for pathologic stage and grade, however, PSMs were associated with BCR but not long-term oncologic outcomes. These data confirm that men with apex-only PSMs may not be ideal candidates for adjuvant therapy after RP.

Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?

BACKGROUND: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT). METHODS: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000-2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain. RESULTS: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22-2.30; P=0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01-1.99; P=0.042). CONCLUSIONS: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.

Predicting bone scan positivity in non-metastatic castration-resistant prostate cancer.

BACKGROUND: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. METHODS: Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations. RESULTS: A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾ 50 ng ml(-1), respectively (P-trend <0.001). Men with PSADT ⩾ 15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan. CONCLUSIONS: PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.

Utilization of bone scans in conjunction with prostate-specific antigen levels in the surveillance for recurrence of adenocarcinoma after radical prostatectomy.

Follow-up evaluation of patients who have undergone radical prostatectomy routinely consists of serial bone scintigraphy and, more recently, prostate-specific antigen (PSA) levels. The utility of serial bone scans in combination with PSA levels is retrospectively reviewed in 118 men treated by radical prostatectomy for clinical Stage A or B disease who, at the time of surgery, had no evidence of metastatic disease. Of the 118 patients, 75.4% had no abnormality on either test (mean follow-up 32.4 mo), 9.3% demonstrated a detectable or rising PSA level with negative bone scan (mean follow-up 35 mo), and 8.5% exhibited a detectable and or rising PSA level and positive bone scan (mean follow-up 30.7 mo). Follow-up bone scans were read as either positive or indeterminate with undetectable PSA levels in 6.8% of patients (mean follow-up 27.3 mo). Critical review of the equivocal studies suggests that postoperative PSA levels more truly represent the clinical situation than bone scans. Following radical prostatectomy, routine bone scintigraphy provides little additional information when PSA levels are negative. If PSA becomes detectable or the patient develops symptoms, bone scintigraphy should then be performed.

Human papillomavirus detection by polymerase chain reaction in benign and malignant prostate tissue is dependent on the primer set utilized.

OBJECTIVES: Prior investigations evaluating the presence of human papillomavirus (HPV) in prostatic tissue by polymerase chain reaction (PCR) technology have yielded detection rates of 0% to 100%. Contamination by viral DNA from prostatic urethral colonization or less than optimal laboratory conditions have been suggested to explain this discrepancy. In addition, the various investigations have differed in the specific oligonucleotide primers utilized for amplification and, therefore, have searched for different segments of the viral genome. The objective of this study is to address these differences. METHODS: Forty-one archival radical prostatectomy specimens were evaluated, identifying areas of normal and abnormal histology. Meticulous technique was used during tissue acquisition, histologic confirmation, DNA isolation, PCR amplification, polyacrylamide gel electrophoresis, and staining. Primers for a 126- and 99-base pair (bp) fragment of the E6 portion of HPV 16 as well as a consensus primer for the L1 portion of the papillomavirus genome were utilized. RESULTS: Of the normal prostatic tissues, 13.5% (5/37) contained the 126-bp E6 viral DNA as did 33.3% (7/21) of benign prostatic hyperplasia (BPH) samples, 25% (5/20) of dysplasia, 18.2% (2/11) of Gleason grades 1 and 2 adenocarcinoma, 25.9% (7/27) of Gleason grade 3 adenocarcinoma, and 6.7% (1/15) of Gleason grade 4 adenocarcinoma. Sections from the urethras of the prostatectomy specimens contained viral DNA in 31.7% (13/41). Viral detection was variable among different specimens in the same patient. With amplification for the 99-bp fragment of HPV 16, 1 of 37 normal (2.7%), 2 of 21 BPH (9.5%), 1 of 20 dysplasia (5.0%), and 2 of 53 cancer (3.8%) specimens revealed HPV DNA. In none of the specimens was DNA amplified using primers for a 450-bp fragment of the L1 portion of HPV. CONCLUSIONS: Previously published discrepancies in HPV detection may be solely due to the differences in primer sets utilized.

Transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate.

OBJECTIVES: Although the clinical presentation and physical examination findings in patients with lymphoma or leukemia involving the prostate have been described previously, the transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate has not been previously described. METHODS: Nine patients with prostate cancer diagnosed by transrectal ultrasound-guided prostate biopsies were found to have hematolymphoid malignancies involving the prostate at the time of subsequent radical prostatectomy and pelvic lymph node dissection. The ultrasound images and prostate needle biopsy results are presented. RESULTS: Prospective analysis of transrectal ultrasound images revealed no abnormality other than hypoechogenicity typical of prostate cancer in 7 of the 9 patients (77.8%). In 2 patients, the ultrasound images were free of any abnormalities. In 2 of the 9 patients (22.2%), the prostate needle biopsies demonstrated suspicious lymphocytic infiltrate in addition to prostate cancer. CONCLUSIONS: Transrectal ultrasound does not detect hematolymphoid malignancies involving the prostate. Ultrasound-guided biopsies of the prostate have a very low rate of detecting these malignancies.

Correlation of transrectal ultrasound measurements of prostate and transition zone size with symptom score, bother score, urinary flow rate, and post-void residual volume.

OBJECTIVES: To assess the correlation of total prostatic size and prostate transition zone dimensions with various measurements of the severity of bladder outlet obstruction secondary to benign prostatic hyperplasia. METHODS: Prostate-specific antigen, creatinine, American Urological Association symptom score, bother score, urinary history, uroflowmetry, and post-void residual urine volume determination was followed by measurement of the prostate gland and transition zone on transrectal ultrasound images in 136 men undergoing systematic prostate biopsies. Patients were divided into five groups based on past urinary tract treatment history and the presence of prostate cancer on the biopsies. The total prostate and transition zone dimensions, as well as calculated prostate and transition zone volumes, were compared by Pearson correlation with both the subjective and objective voiding parameters in each patient group. RESULTS: The transition zone dimensions correlated positively with American Urological Association symptom score, bother score, and post-void residual urine volume and correlated negatively with maximum and mean flow rates, particularly in patients with no history of prostate surgery, alpha-blocker administration, urinary infections, irritative voiding symptoms, or prostate cancer. CONCLUSIONS: Transrectal ultrasound measurements of transition zone dimensions correlate better than total prostatic dimensions or calculated prostatic or transition zone volumes with the severity of benign prostatic hyperplasia. Of these, the transverse transition zone dimension demonstrated the best correlation; however, this correlation is probably not adequate for clinical utility.

Comparison of prostate size in university and Veterans Affairs Health Care System patients with negative prostate biopsies.

OBJECTIVES: Many important prostate studies take place at Veterans Affairs hospitals. We have examined whether the patient population at these institutions is comparable to the population presenting for prostate evaluation at university hospitals. METHODS: We included all patients presenting for transrectal ultrasound (TRUS) and biopsy in whom systematic biopsies failed to reveal prostate cancer at both Stanford University Medical Center (90 patients) and the Palo Alto Veterans Affairs Health Care System (103 patients) from August 1, 1995 to July 31, 1996. Identical techniques and equipment for TRUS examination and prostate size determination were used at both institutions. RESULTS: There was no significant difference in the age or prostate-specific antigen (PSA) levels of the patients at the two institutions. The mean prostatic volume of the Stanford University patients was 71 cm3 (median 63 cm3), whereas the mean prostatic volume of patients at the Palo Alto Veterans Affairs hospital was 52 cm3 (median 43 cm3), a highly statistically significant difference (P = 0.0009). CONCLUSIONS: The smaller size of the prostate glands in Veterans Affairs patients may be the result of differences in referral base, socioeconomic factors, or environmental factors. These data may have significance for trials conducted only on the prostates of men who are seen at Veterans Affairs hospitals.

Comparison of ultrasound imaging in patients undergoing transperineal and transrectal prostate ultrasound.

OBJECTIVES: Prostatic evaluation in men who have undergone prior abdominoperineal resection pose an unusual challenge for the urologist. Neither digital rectal examination nor transrectal ultrasound (TRUS) can be performed. Transperineal ultrasound (TPUS) has been suggested as an alternative means of imaging. This imaging modality was compared directly with the standard TRUS method. METHODS: TPUS was performed with a 4-MHz abdominal probe or biplane multiple frequency probe at a frequency of 5 to 7 MHz followed by TRUS at 7 MHz in 50 consecutive men referred for prostate ultrasound and biopsy who had not undergone prior abdominoperineal resection. Dimensions of the prostate and ultrasound findings such as hypoechoic, anechoic, or hyperechoic areas were noted for each sonographic approach. Volume calculation was performed by the prolate spheroid method. RESULTS: There was good TPUS visualization of the prostate in the transverse plane in 48 (96%) of 50 patients and in the sagittal plane in 45 (90%) of 50 patients. Prostate volume calculation by TPUS correlated well with the volume calculated by TRUS (r=0.876). Twenty-nine patients (58%) were found to have suspicious hypoechoic lesions by TRUS; none were seen by TPUS. Prostatic calcifications were present in 12 patients and were visualized by both TPUS and TRUS in all 12 patients. Six prostate glands demonstrated cystic lesions on TRUS imaging; three of these cystic lesions were also seen with TPUS imaging. CONCLUSIONS: TPUS allows visualization of the prostate with volume determination that is comparable to the volume determination by TRUS. Some intraprostatic findings such as calcifications and cysts can be identified; however, suspicious hypoechoic lesions were not identified by TPUS imaging of the prostate.

Prediction of prostate cancer volume using prostate-specific antigen levels, transrectal ultrasound, and systematic sextant biopsies.

OBJECTIVES: Prostate-specific antigen (PSA) levels, transrectal ultrasound, and systematic sextant biopsies have each shown limited ability to predict prostate cancer volume. In combination, these studies may allow more accurate estimation of volume and prognosis. METHODS: One hundred twenty-four patients were evaluated prior to radical prostatectomy. Interactive stepwise multiple regression and separate logistic regression analysis were performed for prediction of prostate cancer volume and volume range. RESULTS: The cancer volumes calculated correlated with the volumes in the radical prostatectomy specimens with R2 of 0.76. Cancers were predicted to be in the volume range associated with poor prognosis (more than 12 cc) or clinically insignificant cancer (less than 1.0 cc) with bias corrected error rates of 5.3% and 10%, respectively. CONCLUSIONS: The formula for prediction of cancer volume correlates well with actual cancer volume in 92 patients but is not adequate to predict volume for an individual patient. The formulas for prediction of volume range show promising predictive ability and may be useful if the extent of disease is unclear.

Is there a difference in outcome after radical prostatectomy between patients with biopsy Gleason sums 4, 5, and 6? Results from the SEARCH database.

PURPOSE: Fewer patients newly diagnosed with prostate cancer today have biopsy Gleason sums <6 compared to several years ago. Several tables and nomograms for predicting disease recurrence after definitive therapy provide little or no discrimination between biopsy Gleason sums 4, 5, and 6. We sought to examine the significance of biopsy Gleason sum for predicting biochemical failure following radical prostatectomy (RP) for men with biopsy Gleason sums of 4, 5, and 6. MATERIALS AND METHODS: We examined data from 988 men treated with RP between 1988 and 2002 who had biopsy Gleason sums of 4-6. Clinical and pathological variables as well as outcome information were compared between men with biopsy Gleason sums of 4-6. The log-rank and Cox proportional hazards analysis were used to determine whether biopsy Gleason sum provided unique prognostic information for men with low biopsy Gleason sums undergoing RP. RESULTS: There was statistically significant, but overall weak correlation between biopsy Gleason sum and Gleason sum of the RP specimen (Spearman's r=0.277, P<0.001). As biopsy Gleason sum increased from 4 to 5 to 6, there was a steady rise (HR=1.31 for each one point increase in Gleason sum, Cox's model) in the risk of PSA failure (P=0.025, log-rank). On multivariate analysis comparing biopsy Gleason sum, preoperative PSA, clinical stage, year of surgery, percent of biopsy cores positive, and age for their ability to predict time to biochemical recurrence, only PSA (HR 2.09, CI 1.56-2.80, P<0.001) and biopsy Gleason sum (HR 1.33, CI 1.05-1.70, P=0.019) were significant independent predictors of PSA failure. CONCLUSIONS: Despite weak correlation between biopsy and pathologic Gleason sum among men with biopsy Gleason sum 4-6 tumors, grade was a significant independent predictor of PSA failure following RP. In the range of 4-6, biopsy Gleason sum acted as a continuous variable for predicting PSA failure. The routine use of Gleason sums 4 and 5 to grade prostate needle biopsy specimens should not be abandoned.

Predicting bone scan positivity after biochemical recurrence following radical prostatectomy in both hormone-naive men and patients receiving androgen-deprivation therapy: results from the SEARCH database.

BACKGROUND: To evaluate the factors associated with positive bone scans after biochemical recurrence (BCR) following radical prostatectomy in both hormone-naive subjects and subjects after androgen-deprivation therapy (ADT). METHODS: Retrospective analysis of 380 bone scans of 301 hormone-naive subjects and 214 bone scans of 137 subjects after ADT following BCR from the Shared Equal Access Regional Cancer Hospital database. Generalized estimating equations and local regression plots were used to evaluate bone scan positivity by patients' demographics, pathological features, PSA levels and kinetics. RESULTS: Among hormone-naive subjects and subjects on ADT, bone scan positivity was seen in 24 (6%) and 65 (30%) subjects, respectively. In hormone-naive subjects, the higher prescan PSA, higher PSA velocity (PSAV) and shorter PSA doubling time (PSADT) were significantly associated with positive scans (P=0.008, P<0.001 and P<0.001, respectively). In subjects after ADT, the prescan PSA, PSAV and PSADT were significantly associated with positive scans (P=0.011, P<0.001 and P=0.002, respectively). Regression plots showed increased scan positivity with increasing PSA levels and shortening PSADT (all P<0.001) for both hormone-naive subjects and subjects after ADT. For a given PSA level and PSADT, subjects on ADT had higher bone scan positivity. CONCLUSIONS: In both hormone-naive subjects and subjects after ADT, more aggressive and advanced disease identified by higher PSA levels, higher PSAV and shorter PSADT were associated with higher bone scan positivity. For the same PSA level and PSADT, subjects after ADT had higher bone scan positivity than hormone-naive subjects. Therefore, PSA levels and kinetics may be used as selection criteria for bone scan in these patients.

High level of dioxin-TEQ in tissue is associated with Agent Orange exposure but not with biochemical recurrence after radical prostatectomy.

BACKGROUND: Agent Orange (AO) was previously identified as a significant risk factor for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer patients. In this study, we determined the levels of dioxin biological toxicity using toxic equivalency (TEQ) values and examined the impact of dioxin-TEQ level on BCR. METHODS: A total of 93 men who underwent RP, with a median of 5.3 years of postoperative follow-up, were included in the study. The dioxin-TEQ level of each patient was measured using intraoperatively harvested abdominal subcutaneous fat. The dichotomous categorization of dioxin-TEQ by the 50th percentile (low<50% vs high 50%) was also used to regroup the patient cohort, regardless of the previous history of AO exposure. Comparisons between the dioxin-TEQ levels, clinicopathological characteristics and BCR in AO-exposed and -unexposed men were made to allocate possible risk factors. The multivariable logistic regression model was used to identify significant risk factors associated with BCR, adjusting for other confounding factors. RESULTS: The median dioxin-TEQ level in 37 AO-exposed patients was significantly higher than that in 56 unexposed patients (22.3 vs 15.0 pg g(-1) fat, respectively, P<0.001). The men with AO exposure were more likely to have a high dioxin-TEQ level (P<0.001). Neither AO exposure nor the level of dioxin-TEQ was associated with BCR. Tumor stage (T3/T4 vs T2) and Gleason grade (Gleason 3+4) were independent risk factors for BCR after RP. CONCLUSIONS: Exposure to AO significantly increases the adipose level of dioxin-TEQ in patients treated with RP. However, exposure to AO or a high dioxin-TEQ level was not associated with an increased risk of BCR after RP. This lack of association supports the current conclusion that the evidence of carcinogenicity of AO in prostate cancer patients is not sufficient and remains 'limited'.

Emerging association between androgen deprivation therapy and male meningioma: significant expression of luteinizing hormone-releasing hormone receptor in male meningioma.

BACKGROUND: There is emerging data suggesting a potential risk for meningioma growth stimulation in patients on luteinizing hormone-releasing hormone (LHRH) analogs for prostate cancer. We examined the expression of LHRH receptor (LHRH-R), progesterone receptor (PR) and Ki67 labeling index (LI) in specimens from male meningioma (MM) and female meningioma (FM) patients. METHODS: A total of 24 MM and 24 FM paraffin blocks were retrieved from our institution between 1991 and 2008. Sections from the paraffin blocks were stained with mouse monoclonal antibodies against LHRH-R, PR and Ki67. All male patients had no previous history of prostate cancer (PCa) or previous history of hormone therapy. RESULTS: LHRH-R positivity was extensive in 92% of MM and 88% of FM samples, with both showing strong intensity (67% and 79%, respectively). PR was positive in 20 of 24 (83%) MM and 23 of 24 (96%) FM samples. MM is less likely to exhibit Ki67 LI >4% compared with FM. CONCLUSIONS: The majority of MM and FM samples were strongly positive for LHRH-R expression and PR expression. The emerging association of androgen deprivation therapy and meningioma growth should be recognized in urological practice. Caution should be taken when considering LHRH agonist administration for patients with PCa and concurrent meningioma or previous history of meningioma.

Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database.

BACKGROUND: While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP). METHODS: We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses. RESULTS: Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5). CONCLUSIONS: Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database.

BACKGROUND: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. METHODS: We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. RESULTS: In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining ≥ 2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI): 1.03-2.64, P=0.04) while weight loss ≥ 2.5 kg was not associated with BCR (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41). CONCLUSIONS: As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain ≥ 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain ≥ 2.5 kg may promote prostate cancer progression.

The influence of hepatic function on prostate cancer outcomes after radical prostatectomy.

Prostate growth is dependent on circulating androgens, which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2 and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum > or =7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; P=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade, but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing RP. The effect of moderate-to-severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.

The effect of race on the discriminatory accuracy of models to predict biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital and Duke Prostate Center databases.

To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015-0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (-0.036; range -0.078 to -0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3-4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race.