Koji Okihara

Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy

OBJECTIVESnTo evaluate the factors influencing the cancer detection rate in men whose initial and repeat biopsies were both performed using an extended multisite biopsy scheme. Sextant biopsy of the prostate is associated with a significant false-negative rate, as evident from the high cancer detection rate after repeat prostate biopsy. Extended multisite biopsy schemes have therefore been recommended to maximize cancer detection.nnnMETHODSnBetween June 1997 and August 2001, 939 men underwent prostate biopsy for early detection of prostate cancer using the extended multisite scheme (10 or 11 cores incorporating the anterior horn of the peripheral zone with or without midline peripheral zone and/or the transition zone). Of these 939 men, 89 (9.5%) underwent a repeat extended multisite prostate biopsy. The median prostate-specific antigen level was 6.9 ng/mL (range 0.7-36.1). Twenty-four men (27%) had an abnormal digital rectal examination at presentation. Most men (86%) in the group undergoing repeat biopsy had two or more risk factors for a positive biopsy. The median interval between biopsies was 4 months.nnnRESULTSnOf the 89 men, 15 (17%) had prostate cancer in the repeat biopsy specimen. Seven cancers (47%) were found only in the alternate biopsy sites, 5 (33%) cancers were found only in the sextant sites, and 3 in both sextant and alternate sites. Cancer was present in only one biopsy core in 11 (73%) of the 15 men, and the median Gleason score was 6 (range 6-8). On multivariate analysis, the presence of atypical glands suspicious for carcinoma (AGSC) was the only independent predictor of cancer in repeat biopsy (P <0.004). Of the 79 men without AGSC in the initial biopsy, 8 (10%) had a positive repeat biopsy. The total and percent free prostate-specific antigen level, digital rectal examination, ultrasound findings, and presence of high-grade prostatic intraepithelial neoplasia were not predictive of cancer detection.nnnCONCLUSIONSnThe probability of a positive result for a repeat prostate biopsy is lower after an initial extended multisite biopsy compared with an initial sextant biopsy. The presence of AGSC was the only significant predictor of cancer in the repeat biopsy. Because nearly 50% of cancers detected in the repeat biopsy were in alternate sites only, using a sextant biopsy scheme for repeat biopsy would have missed these cancers.

COMPARATIVE ANALYSIS OF COMPLEXED PROSTATE SPECIFIC ANTIGEN, FREE PROSTATE SPECIFIC ANTIGEN AND THEIR RATIO IN DETECTING PROSTATE CANCER

PURPOSEnWe evaluate the diagnostic use of total, free and complexed serum prostate specific antigen (PSA), and their ratios for enhancing the specificity in detecting prostate cancer.nnnMATERIALS AND METHODSnA total of 354 nonconsecutive men undergoing prostate biopsy were eligible for this retrospective and prospective study. Cancer was found in 122 of these 354 men (34%). Receiver operating characteristics curve analyses were used to calculate and compare the performance of total PSA (Hybritech, San Diego California and Bayer, Tarrytown, New York), complexed PSA (Bayer), percent complexed PSA and percent free PSA. In addition, sensitivity and specificity were calculated and compared.nnnRESULTSnThe area under the receiver operating characteristics curve was highest for percent free PSA, followed by percent complexed PSA, complexed PSA and the 2 total PSA assays (Hybritech and Bayer). The cutoff value of 3.45 ng./ml. for complexed PSA detected the same number of cancers and resulted in 1 additional false-positive case compared with a Hybritech total PSA threshold of 4.0 ng./ml. At sensitivities of 80% to 95%, there were no significant differences for detection comparing the corresponding specificities between Hybritech total PSA and complexed PSA for all 354 men. Complexed PSA alone did not enhance the overall diagnostic accuracy compared with percent free PSA in the Hybritech total PSA range between 4.01 and 6.00 ng./ml., between 6.01 and 10.00 ng./ml., and between 2.50 and 6.00 ng./ml. At sensitivities of 80% to 95% specificity of percent complexed PSA was almost identical to that of percent free PSA except for the Hybritech total PSA range less than or equal to 4.00 ng./ml.nnnCONCLUSIONSnThis study suggests complexed PSA is equivalent to total PSA for the early detection of prostate cancer. Percent free PSA outperforms complexed PSA and percent complexed PSA performed equivalently to percent free PSA in all total PSA ranges analyzed between 2.5 and 10 ng./ml.

Outcome Of Patients With Gleason Score 8 Or Higher Prostate Cancer Following Radical Prostatectomy Alone

PURPOSEnWe determine the effect of clinical and pathological variables on the outcome of patients with prostate cancer of Gleason scores 8 or greater treated with radical prostatectomy alone.nnnMATERIALS AND METHODSnBetween April 1987 and October 1998, 1,199 patients underwent radical retropubic prostatectomy. We identified 188 patients assigned a Gleason score of 8 or higher in the prostatectomy specimen who did not receive any neoadjuvant or adjuvant therapy. Median followup was 60 months (range 1 to 129). Disease recurrence was defined as any detectable prostate specific antigen level 0.1 ng./ml. or greater.nnnRESULTSnOf 188 patients 128 (68%) had no evidence of prostate cancer after a median followup of 60 months, while 60 (32%) demonstrated a detectable PSA level. There were 58 (31%) patients with disease confined to the prostate with negative surgical margins while 108 (57%) had prostate cancer confined to the surgical specimen. Positive surgical margin with extraprostatic extension was seen in 16 (9%) patients and seminal vesicle invasion was present in 40 (21%). The 5 and 7-year disease-free survival rates for the entire cohort were 71% and 55%, respectively. Patients with specimen confined disease had a significantly higher 5-year disease-free survival rate than those with nonspecimen confined disease (84% and 50%, p <0.0001). On multivariate analysis pathological status of the surgical specimen was the most significant independent predictor of disease recurrence. Age, ethnicity, clinical stage and preoperative PSA had no independent effect on disease recurrence.nnnCONCLUSIONSnLong-term disease-free survival can be expected in those patients with high grade prostate cancer whose disease is confined to the prostate and/or the surgical specimen.

CAN COMPLEXED PROSTATE SPECIFIC ANTIGEN AND PROSTATIC VOLUME ENHANCE PROSTATE CANCER DETECTION IN MEN WITH TOTAL PROSTATE SPECIFIC ANTIGEN BETWEEN 2.5 AND 4.0 NG./ML.

PURPOSEnWe assessed whether complexed prostate specific antigen (PSA) and complexed PSA referenced variables would enhance prostate cancer detection in men with serum total PSA between 2.5 and 4.0 ng./ml.nnnMATERIALS AND METHODSnTransition zone and total prostate gland volumes were determined in 151 men who underwent prostate biopsy using an 11 core biopsy strategy. In addition to measuring the Bayer section sign complexed PSA assay, we also calculated 2 computed complexed PSA values (Hybritech parallel total PSA--Hybritech free PSA and Bayer total PSA--Hybritech free PSA). We calculated 8 volume referenced variables using total and complexed PSA, and 2 computed complexed PSA values by dividing each value by the total prostate and transition zone volumes.nnnRESULTSnOf the 151 patients 37 (24.5%) had cancer. In 10 of the 37 men with cancer (27%) a positive core was present in only 1 or more of the 5 alternate regions not sampled by conventional sextant biopsies. At 92% sensitivity a cutoff value of 2.3 ng./ml. for complexed and 31% for free-to-total PSA provided 42% and 11% specificity, respectively (p <0.001). In the 116 men with a total prostate volume of 30 cc or greater at 92% sensitivity the specificity of complexed PSA density (55%) and complexed PSA adjusted for transition zone volume (52%) were better than that of complexed (40%) and free-to-total (11%) PSA. In the 35 men with a total prostate volume of less than 30 cc at 92% sensitivity the specificity of complexed PSA (50%), complexed PSA density (55%) and complexed PSA adjusted for transition zone volume (55%) were significantly better than that of free-to-total PSA (8%, p <0.001). The area under the curve of complexed PSA was almost identical to that of the 2 computed complexed PSA calculations.nnnCONCLUSIONSnA substantial proportion of men with total PSA values between 2.5 and 4.0 ng./ml. had prostate cancer. Complexed and computed complexed PSA were more specific than the free-to-total PSA ratio when total PSA was between 2.5 and 4.0 ng./ml. A 2.3 ng./ml. threshold for complexed and computed complexed PSA appears to stratify prostate biopsy results in men with total PSA between 2.5 and 4.0 ng./ml. The computed complexed PSA calculation appears to be equivalent to the complexed PSA serum assay for detecting cancer. Volume referenced complexed PSA performed better than complexed PSA in men with a total prostate volume of 30 cc or greater compared to men with a total prostate volume of less than 30 cc.