Efficacy of prostatic fossa biopsy in detecting local recurrence after radical prostatectomy.

OBJECTIVES: To evaluate retrospectively the efficacy of prostatic fossa biopsy in detecting local recurrence of prostate cancer in men with biochemical failure after radical prostatectomy. METHODS: Between January 1997 and December 2002, 100 men without prior adjuvant therapy after radical prostatectomy underwent transrectal ultrasound (TRUS)-guided biopsy of the prostatic fossa. The TRUS findings, digital rectal examination (DRE) findings, serum total prostate-specific antigen (PSA) level at TRUS, PSA velocity, and pathologic stage and Gleason score of the radical prostatectomy specimen were correlated with the biopsy results. RESULTS: Overall, 29 (29%) of the 100 men who underwent biopsy had documented local recurrence. The sensitivity and specificity of DRE to detect biopsy-proven local recurrence was 72.4% and 64.8%, respectively. The corresponding values for TRUS were 86.2% and 53.5%. None of the men with a serum PSA concentration of less than 0.5 ng/mL at biopsy who had normal results for both TRUS and DRE had a biopsy-proven local recurrence. By stepwise multivariate logistic regression analysis, abnormal TRUS findings and serum PSA concentration at biopsy were independent predictors for positive fossa biopsy results. The combination of TRUS and serum PSA concentration was the best predictive model for a positive fossa biopsy result. CONCLUSIONS: Prostatic fossa biopsy should be avoided in patients with both or either normal DRE or TRUS findings when the PSA level is less than 0.5 ng/mL.

Transrectal ultrasound versus magnetic resonance imaging for detection of rectal wall invasion by prostate cancer.

BACKGROUND: This study compared the accuracy of transrectal ultrasound (TRUS) versus magnetic resonance imaging (MRI) in the detection of rectal wall involvement by prostate cancer in patients undergoing salvage total pelvic exenteration (TPE) or cystoprostatectomy. METHODS: We identified 16 patients who underwent TPE and 24 patients who underwent cystoprostatectomy for locally advanced prostate cancer as salvage procedures with palliative intent. Patients were examined by TRUS, MRI, or both within the month preceding surgery. Histologic evidence of rectal involvement with prostate cancer was considered the gold standard diagnostic criterion in patients undergoing TPE. Among patients undergoing cystoprostatectomy, posterior prostatic surgical margins and clinical evidence of rectal wall recurrence during a median follow-up duration of 18.6 months were considered the gold standard. The sensitivity, specificity, and overall accuracy with which TRUS and MRI detected rectal wall involvement were compared. RESULTS: Fifteen (93.7%) of the patients who underwent TPE had histologically-proven rectal wall involvement with prostate cancer. Rectal and perineal recurrence developed 10 months after surgery in 1 (4.1%) patient in the cystoprostatectomy group. The sensitivity, specificity, and overall accuracy of TRUS were: 92.9 (66.1-99.8), 87.0 (66.4-97.2), and 89.2 (74.6-97.0), respectively. The sensitivity, specificity, and overall accuracy of MRI were: 54.6 (23.4-83.3), 100 (76.8-100.0), and 80 (59.3-93.2), respectively. CONCLUSIONS: TRUS is a highly sensitive diagnostic modality for rectal wall involvement in patients with locally advanced prostate cancer. Although MRI is very specific, it cannot reliably rule out rectal involvement in the presence of a positive TRUS.

Evidence that transfer of functional p53 protein results in increased apoptosis in prostate cancer.

PURPOSE: INGN 201 (Ad-p53) is a replication-defective adenoviral vector that encodes a wild-type p53 gene driven by the cytomegalovirus promoter. INGN 201 has been shown to have antitumoral activity against human prostate cancer cell lines. This study was undertaken to determine the safety of INGN 201 in patients with locally advanced prostate cancer, to assess transgene expression, and to evaluate antitumoral activity. EXPERIMENTAL DESIGN: Our study included patients with clinical stage T3, T1c-T2a with Gleason score 8-10 disease, or T2a-T2b with Gleason score 7 disease and a prostate-specific antigen level >10 ng/ml. INGN 201 was administered by intraprostatic injection under ultrasonographic guidance. One course of INGN 201 was defined as three separate INGN 201 administrations 2 weeks apart. Biopsies at baseline and 24 h after the first administration were assessed for p53 protein by immunohistochemical staining and for apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: A total of 38 courses of INGN 201 gene therapy were administered to 30 patients, of whom 26 underwent radical prostatectomy. There were no grade 3 or 4 adverse events related to INGN 201 administration. Of the 11 patients with negative baseline immunostaining for p53 protein, 10 had positive p53 immunostaining after the first administration of INGN 201, and 8 had an increase in apoptotic cells by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. All 26 of the patients who underwent radical prostatectomy had significant residual viable prostate cancer, and 12 have experienced biochemical failure (median follow-up, 42 months). CONCLUSION: Intraprostatic INGN 201 gene therapy is safe and can reliably result in p53 protein production and apoptosis.

Role of systematic ultrasound-guided staging biopsies in predicting extraprostatic extension and seminal vesicle invasion in men with prostate cancer.

PURPOSE: To assess the presence of extraprostatic extension and seminal vesicle invasion in men with prostate cancer, we performed systematic staging biopsies targeting neurovascular bundles, seminal vesicles, and other extraprostatic tissues before the men underwent radical prostatectomy. We retrospectively evaluated the clinical efficacy of these systematic staging biopsies compared with digital rectal examination (DRE) and transrectal sonography (TRUS). METHODS: Two hundred forty-four candidates for prostatectomy who had a diagnostic biopsy Gleason score of 8 or higher and/or indications of extraprostatic extension (eg, seminal vesicle invasion) by DRE or TRUS underwent staging biopsies using an 18-gauge Tru-Cut needle under real-time TRUS guidance between June 1997 and March 2000. We determined the number of staging biopsy cores to be taken based on the Gleason score of the diagnostic biopsy as well as abnormal DRE and/or TRUS findings. The chi-square test was used to evaluate the statistical significance of differences. RESULTS: There were no complications of staging biopsy. In 75 (31%) of the 244 patients, results of the staging biopsies were positive. The clinical stage was upgraded by staging biopsy in 18 (24%) of these 75 patients. After the staging biopsies, 90 patients underwent radical prostatectomy. Among these 90 patients, staging biopsy specimens were positive for cancer in 20 (47%) of the 43 patients who received neoadjuvant therapy and in 1 (2%) of the 47 patients who did not receive neoadjuvant therapy. There were no false-positive staging biopsies in either group. Among the 90 patients who underwent radical prostatectomy, the false-negative rate for the prediction of organ-confined disease was 43% (30/69) for staging biopsies compared with 29% (10/34) for TRUS. The diagnostic accuracy of staging biopsies (67%; 60/90) was higher than that of DRE (52%; 47/90; p < 0.05) but lower than that of TRUS (79%; 71/90; p = 0.066). CONCLUSIONS: Staging biopsies can reliably sample extraprostatic tissue, including the seminal vesicles and neurovascular bundles. Positive staging biopsy results can aid in the selection of treatment options and in the prediction of outcome for individual patients by providing definitive histologic confirmation of locally advanced disease. Conventional predictive variables for staging can be applied when the results of staging biopsies are negative.