0022-5347 /92/14 73-0837$03.00 /0 THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC. Vol. 147, 837-8,!,0, March 1992 Printed in U.S.A. THE DISTRIBUTION OF PROSTATE SPECIFIC ANTIGEN IN MEN WITHOUT CLINICAL OR PATHOLOGICAL EVIDENCE OF PROSTATE CANCER: RELATIONSHIP TO GLAND VOLUME AND AGE R. JOSEPH BABAIAN,* HIROAKI MIYASHITA, ROBERT B. EVANS AND EDILBERTO I. RAMIREZ From the Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ABSTRACT We estimated the in vivo prostate gland volume in 408 men (320 without clinical evidence of prostate cancer, and 88 with an abnormal digital rectal examination and/or transrectal prostate ultrasound and negative biopsies) using sequential step-section ultrasound analysis and correlated it to the serum prostate specific antigen (PSA) value. Of the men 331 (81.1 %) had a PSA value of 4 ng./ml. or less. The PSA value was greater than 4 but less than or equal to 10 in 64 men (15.7%) and greater than 10 in 13 (3.2% ). The men were subclassified by prostate gland volume at arbitrary break points. A total of 139 men (34.1 %) had a gland of 25 cm. 3 or less, 2.2% of whom had a PSA value of greater than 4. Further analysis revealed that the incidence of a PSA value greater than 4 increased as the prostate volume increased (18.4% for greater than 25 but less than or equal to 50, and 65.4% for greater than 50) and as age increased. We found a statistically significant association between prostate gland volume and patient age (p <0.00005) to the serum PSA concentration. The finding of a PSA value of greater than 10 was uncommon regardless of the prostate gland volume. Clinical implications of these results are discussed, and a statistical model to estimate the serum PSA by gland volume and patient age was constructed. KEY WORDS: prostatic diseases; ultrasonic diagnosis; palpation; antigens, neoplasm The recommended upper range of normal for the monoclonal prostate specific antigen (PSA) assay is 4 ng./ml. Several investigators have demonstrated that approximately 20% of the men without presumed prostate cancer have a PSA value that exceeds 4 ng./ml. 1 • 2 Stamey et al have shown that benign prostatic hyperplasia (BPH) can be associated with elevated levels of PSA as determined by a polyclonal assay. 3 However, there are sparse data that correlate the serum PSA value with the in vivo estimated prostate gland volume in men who have no clinical suspicion of prostate cancer, or in men who have either an abnormal digital rectal or transrectal prostate ultra- sound examination plus a biopsy sample negative for prostate cancer. Because prostate gland volume can be estimated accu- rately with transrectal ultrasound 4 • 5 we studied whether there was a relationship between the serum PSA value and prostate gland volume determined by ultrasound. The clinical implica- tions of the observed relationship are discussed. MATERIAL AND METHODS Between July 1987 and December 1989, 429 men with nega- tive prostate examinations or negative prostate biopsies were seen at the prostate cancer detection clinic at our university cancer center. Of these men 21 had abnormal studies and were excluded from this study because they did not undergo biopsy (positive transrectal ultrasound in 11, digital rectal examina- tion in 9 or both in 1). This report is based on the remaining 408 men, 88 of whom had an abnormal digital rectal examina- tion and/or transrectal ultrasound and a negative prostate biopsy. Each examinee underwent evaluation with a PSA de- termination, digital rectal examination and transrectal ultra- sound. A blood sample was drawn from each man, all of whom were outpatients, and a PSA determination was performed on the serum using the monoclonal enzyme immunoassay. t Trans- rectal ultrasound was performed with the patient in the left Accepted for publication May 24, 1991. *Requests for reprints: Department of Urology, Box 110, The Uni- versity of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030. t Hybritech, San Diego, California. 837 lateral decubitus position using the Bruel and Kjaer 1846 ultrasound machine. As part of this examination a planimetric (step-section) estimation of prostate gland volume was per- formed with a 5 mm. (July 1987 to May 1989) or a 2 mm. (June 1989 to December 1989) stepping unit and a 7 MHz. axial transducer (Bruel and Kjaer 8539). All volume estimates were performed by the same investigator (R. B. E.). The planimetric method is accomplished by estimating the sequential areas of the prostate at a fixed distance from the base of the gland to the apex using a stabilized stepping unit upon which the trans- ducer lies. The areas are then added together by the ultrasound machine's computer and the volume is derived. After comple- tion of the ultrasound study a digital rectal examination was performed with the patient in the modified jackknife position. The transrectal ultrasound and digital rectal examinations were performed and interpreted by the same board-certified urolo- gist. The median age of the examinees was 62 years (range 29 to 84 years). The men were either self-referred (343) or physi- cian-referred (65) because of an abnormal digital rectal exam- ination or transrectal ultrasound, or an elevated serum marker. Multiple regression analysis was used to develop 4 mathemat- ical models that relate PSA to prostate gland volume, PSA to patient age, prostate gland volume to patient age, and PSA to prostate gland volume and patient age. PSA and prostate gland volume were logarithmically transformed whenever used as the dependent variable to achieve normalcy. 6 • 7 RESULTS Digital rectal examination and transrectal ultrasound were negative in 320 men. Of the remaining 88 men 57 had an abnormal digital rectal examination, 68 had an abnormal trans- rectal ultrasound and 37 had abnormalities in both diagnostic studies. Of the 320 men 3 underwent a prostate biopsy because of an elevated PSA level. For the purposes of this study all 320 men were considered clinically free of prostate cancer. Some of these men, despite the normal examinations, probably have prostate cancer. All 88 men with an abnormal examination had a prostate biopsy: 48 ultrasound guided, 22 digital guided, and 18 ultrasound and digital guided. All biopsies were negative for