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.

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.

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.

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'.

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.

Preoperative predictors of blood loss at the time of radical prostatectomy: results from the SEARCH database.

The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P<0.001). The mean-adjusted EBL in normal-weight men (BMI<25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BM I>or=35 kg/m(2)). Predicted EBL for men with the smallest prostates (<20 g) was 721 ml, compared to 1326 ml for men with prostates >or=100 g. Finally, statistically significant differences between centers were observed, with mean-adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (<20 g) to the largest prostates (>or=100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion.

Impact of nerve sparing on surgical margins and biochemical recurrence: results from the SEARCH database.

The effects of nerve sparing on the risk of positive surgical margins (PSMs) and biochemical recurrence after radical prostatectomy (RP) remain controversial. We examined data from 1018 men treated by RP between 1988 and 2006 at five centers in the Shared Equal Access Regional Cancer Hospital database. Neither bilateral nor unilateral nerve-sparing techniques were associated with a higher risk of PSM; on multivariate analysis of individual sides, the risk of PSM on either side was not increased by nerve sparing on either side. The risk for biochemical recurrence was not affected by bilateral or unilateral nerve sparing. When used on appropriately selected patients, nerve sparing does not increase the probability of PSM or biochemical recurrence after RP.

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.

Fluorodeoxyglucose positron emission tomography studies in the diagnosis and staging of clinically advanced prostate cancer.

OBJECTIVE: To determine the value of 18F-fluoro-2-deoxyglucose (FDG) positron-emission tomography (PET) studies in evaluating patients with advanced prostate cancer. PATIENTS AND METHODS: FDG-PET scans were taken in 30 patients with advanced prostate cancer 1 h after an injection with 555 MBq of FDG. Patients were scanned from the base of the skull to the inguinal region (including the pelvis). They were also assessed by computed tomography (CT) of the abdomen and pelvis, and bone scintigraphy, to evaluate them for metastases. RESULTS: Thirteen patients had locally extensive prostate cancer and 17 had metastatic disease. Twenty of the 30 patients were positive for radioisotope uptake in the prostate or extraprostatically. The patients with PET-detected prostate cancer were untreated (seven), treated hormonally while they had rising PSA levels (eight), or treated hormonally with a detectable but stable PSA (five). The remaining 10 patients were negative for FDG uptake in the prostate or any metastatic sites; these 10 patients were receiving hormone therapy, with undetectable PSA levels. CONCLUSION: FDG-PET imaging is not a useful test in evaluating advanced prostate cancer in patients being treated and who have an undetectable PSA level. Staging of advanced prostate cancer may be enhanced by FDG-PET imaging in patients who are untreated, who have had an incomplete response to therapy, or who have a rising PSA level despite treatment.

Prostate cancer detection in veterans with a history of Agent Orange exposure.

PURPOSE: Agent Orange, a chemical that was widely used in the Vietnam War as a defoliant, is widely accepted as a health hazard but its potential causative role in prostate cancer has been controversial. We evaluated the rate of prostate cancer in veterans referred for prostate biopsy who reported a history of Agent Orange exposure compared to the rate in veterans who denied such exposure. MATERIALS AND METHODS: A total of 400 consecutive veterans referred for prostate needle biopsy in a 30-month period completed a survey regarding Agent Orange exposure. Of these 400 patients 32 (8%) reported previous exposure to Agent Orange. From the remaining 368 patients who denied Agent Orange exposure 3 consecutive age matched controls were selected per each patient reporting exposure for a total of 96 age matched controls. Prostate specific antigen, prostate cancer, cancer grade and length of cancer in the biopsy cores were compared in Agent Orange exposed patients and unexposed controls. To determine whether the patient population referred for biopsy was skewed by proportionally more exposed and referred than unexposed patients those referred for biopsy were compared to the overall adult male veteran population followed at the outpatient clinics at our facility. RESULTS: Of the 32 Agent Orange exposed patients 13 (41%) had prostate cancer, while 33 of the 96 controls (34.4%) had cancer. There was no correlation of Agent Orange exposure with cancer (r = 0.06). There was also no statistically significant difference in the 2 groups in regard to PSA (p = 0.90), cancer (p = 0.15), proportion of well differentiated cancers (p = 0.41) or length of cancer in the biopsy cores (p = 0.34). Compared with the total adult male veteran population followed on an outpatient basis at our facility an average of 1.07% of those with a history of Agent Orange exposure were referred for prostate biopsy yearly versus 1.33% of unexposed patients. CONCLUSIONS: Agent Orange may have a role in the causation of some types of cancer but we identified no significant relationship of prostate cancer with Agent Orange exposure in patients referred for prostate biopsy.

Results of a screening program for prostate cancer in patients scheduled for abdominoperineal resection for colorectal pathologic findings.

OBJECTIVES: Because of the difficulty of accessing the prostate for tissue sampling after surgical removal of the rectum and obliteration of the anus, we started an early detection program for prostate cancer in all men scheduled for abdominoperineal resection. METHODS: Twenty consecutive men were screened for prostatic adenocarcinoma before planned abdominoperineal resection for colorectal pathologic findings. Patients were 48 to 77 years old (mean 66.9). Screening included serum prostate-specific antigen determination and digital rectal examination. Those patients with suspicious findings underwent transrectal ultrasound-guided sextant biopsies of the prostate. RESULTS: One patient was excluded because of a prior history of prostate cancer. Six (31.6%) of the remaining 19 patients demonstrated elevated prostate-specific antigen levels (greater than 4.0 ng/mL); two of these patients also had an abnormal digital rectal examination. Transrectal ultrasound and prostate biopsies in these 6 patients revealed prostatic adenocarcinoma in 3 patients (50% of those undergoing biopsies or 15.8% of those screened). The 13 patients who did not undergo prostate biopsies had prostate-specific antigen levels from 0.4 to 2.4 ng/mL (mean 0.9) and normal prostate glands according to the digital rectal examinations. CONCLUSIONS: Screening for prostate cancer in men 50 years old or older with 10 years or longer life expectancy before they undergo abdominoperineal resection detects a significant number of prostatic malignancies and should be encouraged.

Critical evaluation of the current indications for transition zone biopsies.

OBJECTIVES: Two primary indications for the performance of anteriorly directed transition zone (TZ) biopsies are (a) an elevated prostate-specific antigen (PSA) level and an enlarged, non-nodular prostate and (b) prior negative sextant biopsies of the prostate. These indications are, however, based on a study population evaluated early in the PSA era (1989 to 1992). The current analysis targeted a more contemporary series of patients (1995 to 2000) presenting with these two indications for TZ biopsies, who underwent ultrasound scanning and biopsies by the same examiner and with the same equipment as in the earlier series. METHODS: We evaluated 390 men, 274 (70.3%) of whom underwent sextant plus TZ biopsies for elevated PSA levels and an enlarged, non-nodular prostate; 116 (28.7%) underwent this biopsy strategy because of an elevated or rising PSA in whom prior sextant biopsies had not revealed cancer. RESULTS: Of the 274 patients who underwent initial sextant biopsies plus anterior biopsies for an enlarged, non-nodular prostate, 49 (17.9%) were found to have adenocarcinoma and in only 4 (1.5%) did only the TZ biopsies reveal cancer. Of the 116 patients who underwent TZ biopsies after prior negative sextant biopsies, 36 (31.0%) were found to have prostate cancer and in 11 (9.5%) only the TZ biopsies demonstrated cancer. CONCLUSIONS: The cancer detection rate for sextant plus TZ biopsies in this contemporary series of patients presenting with enlarged, non-nodular prostates was substantially lower than the rate in earlier reports (1.5% compared with 36.9%), despite the consistency in the equipment and examining physician. This may have been due to the stage migration of prostate cancer, which has been observed as a result of the widespread use of PSA measurement for early detection. Sextant plus TZ biopsies are more productive in patients with prior negative biopsies who have a persistent clinical suspicion for prostate cancer on the basis of an elevated and/or rising PSA level.