Martha K. Terris

Random Systematic Versus Directed Ultrasound Guided Transrectal Core Biopsies of the Prostate

Random systematic ultrasound guided transrectal core biopsies of the prostate were compared to directed biopsies of specific hypoechoic defects in 136 men with abnormal prostates on digital rectal examination. Prostate cancer was diagnosed in 83 of 136 patients (62 per cent). In 80 of 83 individuals (94 per cent) the cancer was detected by random systematic biopsies alone. Of 57 men in whom random systematic and directed biopsies were obtained the results of biopsy agreed in 86 per cent, while in 9 per cent random systematic biopsies found cancers missed by directed biopsies and in 5 per cent directed biopsies diagnosed cancers missed by random systematic prostate biopsies. Ultrasound guided random systematic biopsy is simple and easily learned. When combined with additional directed biopsies of the rare hypoechoic areas not included in the pattern of systematic sampling, it provides a highly accurate means to diagnose prostate cancer, minimizing observer and sampling errors. This technique of prostate mapping with 6, 1.5 cm. cores provides valuable additional information on cancer volume, Gleason grade and the potential location of surgically positive margins, all without compromising the operation or the chance for a surgical cure.

DETERMINATION OF PROSTATE VOLUME BY TRANSRECTAL ULTRASOUND

Estimation of prostate gland volume with transrectal ultrasound may provide important information in the evaluation of benign and malignant prostatic diseases. To determine the most accurate means of volume estimation 150 patients underwent transrectal ultrasound with 15 separate methods of volume estimation. All patients underwent subsequent radical prostatectomy or cystoprostatectomy. Prostate specimen weights were compared with the results of each volume estimation method. Step-section planimetry, previously assumed to be the most accurate means of volume measurement, exhibited a Pearson correlation coefficient of 0.93. The elliptical volume, widely used as an alternative to planimetry, demonstrated a correlation coefficient of 0.90. The most accurate method to estimate prostate weight (r = 0.94) was a variation of the prolate spheroid formula, expressed as pi/6 (transverse dimension)2 (anteroposterior dimension). When different volume ranges were considered, this prolate spheroid formula provided the closest estimate of weight in glands of less than 40 gm. and those in the 40 to 80 gm. range. The most accurate method to estimate prostates weighing greater than 80 gm. was the formula pi/6 (transverse dimension)3.

RISKS AND COMPLICATIONS OF TRANSRECTAL ULTRASOUND GUIDED PROSTATE NEEDLE BIOPSY: A PROSPECTIVE STUDY AND REVIEW OF THE LITERATURE

PURPOSE Transrectal ultrasound guided needle biopsy of the prostate is routinely performed to diagnose and stage prostate cancer. We prospectively evaluated the true incidence of complications and identified risk factors of needle biopsy. MATERIALS AND METHODS We prospectively studied 128 patients who underwent transrectal ultrasound guided needle biopsy. A pre-biopsy questionnaire provided demographic information. Immediate complications were recorded by the surgical team at the procedure. Information on delayed complications was obtained by telephone interview. Univariate and multivariate analyses were performed. RESULTS There was 1 major and 135 minor complications in 77 patients with at least 1 complication in 63.6%. Most patients tolerated the procedure with minimal discomfort regardless of the number and location of biopsies but younger patients had significantly more discomfort than older men (R = -0.26, p = 0.005). The most common complication was persistent hematuria in 47.1% of cases. None of the hemorrhagic complications was related to previous aspirin or nonsteroidal anti-inflammatory drug use, or the total number of biopsies performed. Infectious complications were rare with only a 1.7% incidence of fever. This rate was associated with the choice of antibiotic combination used (R = 0.25, p = 0.006). CONCLUSIONS Transrectal ultrasound guided needle biopsy is safe for diagnosing prostate cancer with few major but frequent minor complications. Patients are likely to have persistent hematuria for up to 3 to 7 days after the procedure. Recent use of aspirin or nonsteroidal anti-inflammatory drugs is not an absolute contraindication for this procedure. Additional analgesics are not required in patients who undergo anterior or multiple biopsies but they may be useful in younger patients.

Impact of Obesity on Biochemical Control After Radical Prostatectomy for Clinically Localized Prostate Cancer: A Report by the Shared Equal Access Regional Cancer Hospital Database Study Group

PURPOSE Given the limited information regarding the impact of obesity on treatment outcomes for prostate cancer, we sought to examine the relationship between body mass index (BMI) and cancer control after radical prostatectomy (RP). PATIENTS AND METHODS We compared clinicopathologic and biochemical outcome information across BMI groups from 1,106 men treated with RP between 1988 and 2002. Multivariate analysis was used to determine if BMI significantly predicted adverse pathology or biochemical recurrence. RESULTS Obesity was related to year of surgery (P <.001) and race (P <.001), with black men having the highest obesity rates. Obese patients had higher biopsy and pathologic grade tumors (P <.001). On multivariate analysis, BMI > or = 35 kg/m(2) was associated with a trend for higher rates of positive surgical margins (P =.008). Overweight patients (BMI, 25 to 30 kg/m(2)) had a significantly decreased risk of seminal vesicle invasion (P =.039). After controlling for all preoperative clinical variables including year of surgery, BMI > or = 35 kg/m(2) significantly predicted biochemical failure after RP (P =.002). After controlling for surgical margin status, BMI > or = 35 kg/m(2) remained a significant predictor of biochemical failure (P =.012). There was a trend for BMI > or = 35 kg/m(2) to be associated with higher failure rates than BMI between 30 and 35 kg/m(2) (P =.053). CONCLUSION The percentage of obese men undergoing RP in our data set doubled in the last 10 years. Obesity was associated with higher-grade tumors, a trend toward increased risk of positive surgical margins, and higher biochemical failure rates among men treated with RP. A BMI > or = 35 kg/m(2) was associated with a higher risk of failure than a BMI between 30 and 35 kg/m(2).

Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer

OBJECTIVES To determine the value of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) studies in the evaluation of patients with organ-confined prostate cancer. This imaging method has previously found little usefulness in localized prostate tumors because of excretion of the isotope into the urine, masking any lower urinary tract lesions. We evaluated this imaging modality using hydration, furosemide, and bladder emptying before the procedure to evacuate the nonspecific isotope in the urine. METHODS FDG PET scans were performed on 24 patients diagnosed with clinically organ-confined prostate cancer. No patient had received any prior treatments for the cancer. FDG PET scans were performed 1 hour after injection of 15 mCi of F-18 deoxyglucose. Patients were scanned from the base of the skull through the inguinal region (including the pelvis). Additional signal attenuation-corrected images of the inguinal region were acquired 30 minutes after intravenous injection of 40 mg of furosemide. The final diagnosis was made by histologic examination, correlative imaging studies, and/or clinical follow-up. RESULTS FDG PET studies were negative in 23 of the 24 organ-confined prostate cancers and the study was only faintly positive in 1 tumor (4.0% sensitivity). CONCLUSIONS FDG PET is not a useful test in the evaluation of clinically organ-confined prostate cancer.

Gene Expression Patterns in Renal Cell Carcinoma Assessed by Complementary DNA Microarray

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Detection of clinically significant prostate cancer by transrectal ultrasound-guided systematic biopsies

Systematic biopsies are a useful, sensitive means to detect carcinoma of the prostate. However, multiple biopsies pose a risk for detecting clinically insignificant prostate cancer, that is those cancers less than 0.5 cc in volume, which occur in approximately 32% of all white men more than 50 years old. Systematic biopsies were positive for cancer in 442 of 816 patients and 60 (14%) demonstrated only a minute focus of cancer (3 mm. or less) in 1 of the 6 biopsy specimens. In 27 patients with these minute foci who underwent radical prostatectomy a wide range of cancer volumes was observed; 30% of these 27 cancers were less than 0.5 cc (15% less than 0.2 cc) and may not have required therapy. Thus, the overall risk of detecting an insignificant cancer is 4.0% with systematic biopsies. Performance of confirmatory biopsies in patients with a minute focus (3 mm. or less) of cancer on initial systematic biopsies resulted in cancers less than 0.5 cc being removed in only 1 of 10 radical prostatectomies (10%, none was less than 0.2 cc). Thus, with the addition of confirmatory biopsies the risk of detecting insignificant cancer is 1.4%. Conservative management is recommended for patients without significant cancer on repeat biopsies in whom initial biopsies have revealed only a minute focus of cancer in 1 of the biopsy cores. We believe that concern is also warranted for patients who have 3 mm. or less of cancer demonstrated by several nonsystematic biopsies directed at a suspicious hypoechoic lesion in whom the digital rectal examination is normal.

Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer

OBJECTIVES Several reports suggest an increased incidence of osteoporosis and concomitant fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer. We sought to estimate the longitudinal effects of ADT on loss of bone density in this cross-sectional study. METHODS Hip and spine bone mineral density (BMD) studies were performed by dual-energy x-ray absorptiometry on 36 patients with prostate cancer. The year 0 cohort (n = 8) consisted of patients who had not yet begun planned ADT. These men were compared to patients receiving ADT who underwent BMD evaluation at year 2 (n = 6), year 4 (n = 7), year 6 (n = 5), year 8 (n = 5), and year 10 (n = 5) of therapy. All BMD values for the patients with prostate cancer were compared to age-matched control subjects. RESULTS Hip BMD was significantly lower in patients on ADT (mean BMD 0.802 g/cm(2)) compared with those not on ADT (mean BMD 0.935 g/cm(2)). Patients at year 0 had hip and spine BMD similar to age-matched control subjects. There was a significant trend for decreased hip BMD with increasing years of ADT (r = 0.46, P = 0.00008). This relationship was more dramatic when hip BMD at each time point was compared to age-matched control subjects (r = 0.55, P = 0.5 x 10(-16)). This bone loss was evident even up to year 10. BMD loss was more dramatic in patients who had undergone surgical castration than those receiving medical ADT (P = 0.08). Patients on intermittent ADT had similar BMD loss as patients on continuous ADT at year 2 and year 4 but demonstrated less bone loss at year 6 (P = 0.07) despite equivalently low testosterone levels. CONCLUSIONS There is diminished BMD with increasing duration of ADT. Continuous ADT and surgical castration may be more deleterious than medical therapy, particularly when the medical therapy is given in an intermittent fashion.

Original Articles: Prostate Cancer: Indications for Ultrasound Guided Transition Zone Biopsies in the Detection of Prostate Cancer

ABSTRACTTransrectal prostate ultrasound and systematic sextant biopsies have improved peripheral zone cancer diagnosis but they may miss many cancers arising in the transition zone. Biopsies directed into the transition zone have been used to detect residual prostate cancer in patients diagnosed by transurethral resection and they have been suggested as potentially useful additions to systematic sextant biopsies. To define the indications for transition zone biopsies 187 men underwent evaluation including systematic sextant biopsies and transition zone biopsies. These patients were classified into 4 categories based on clinical presentation. Category 1 included 26 men with palpable nodularity and an elevated prostate specific antigen (PSA), of whom 16 (61.5%) had positive biopsies but none was positive only in the transition zone biopsies. Category 2 consisted of 49 men with sonographic abnormalities in the transition zone, of whom 15 (30.6%) had positive biopsies, including 2 (13.3%) with only positive t...

Routine Transition Zone and Seminal Vesicle Biopsies in All Patients Undergoing Transrectal Ultrasound Guided Prostate Biopsies are Not Indicated

PURPOSE Transrectal ultrasound guided biopsies of the transition zone and seminal vesicles have been useful in select patients. More widespread use of these additional biopsies has been proposed. The efficacy of routine transition zone and seminal vesicle biopsies was examined. MATERIALS AND METHODS From January 1988 to October 1994, 736 transrectal ultrasound guided systematic sextant biopsies were performed. From October 1994 to July 1995, 161 consecutive patients underwent transrectal ultrasound with systematic sextant, transition zone and seminal vesicle biopsies. RESULTS Of the 736 patients undergoing only sextant biopsies 309 (42.0%) had cancer and 24 (3.3%) required repeat biopsy, compared to 55 (34.2%) and 4 (2.5%) of 161 undergoing combined sextant, transition zone and seminal vesicle biopsies. Prostate cancer was found only in the systematic sextant biopsies in 43 of the former 55 patients (78.2%), and in the transition zone and systematic sextant biopsies in 11 (20.0%). One patient (1.8% of patients with cancer or 0.6% of all 161 patients) had cancer in only the anterior biopsies and 6 (10.9 and 3.7%, respectively) had cancer involving the seminal vesicles. CONCLUSIONS Routine transition zone and seminal vesicle biopsies in all patients undergoing transrectal ultrasound guided systematic sextant biopsies are not warranted.