To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.

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.

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ContextThe recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions.Objective To determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables.Design Retrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992. Setting University hospital.Patients Radical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostatespecific antigen (PSA) level.Main Outcome Measure Biochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing. ResultsCancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the .01 level. ConclusionThe % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression-capsular penetration and positive surgical margins-were not independently predictive of failure after radical prostatectomy.

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Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 102 men before hospitalization for radical prostatectomy. Prostate specimens were subjected to detailed histological and morphometric analysis. Levels of prostate specific antigen were significantly different between patients with and without a Gleason score of 7 or greater (p less than 0.001), capsular penetration greater than 1 cm. in linear extent (p less than 0.001), seminal vesicle invasion (p less than 0.001) and pelvic lymph node metastasis (p less than 0.005). Prostate specific antigen was strongly correlated with volume of prostate cancer (r equals 0.70). Bivariate and multivariate analyses indicate that cancer volume is the primary determinant of serum prostate specific antigen levels. Prostate specific antigen was elevated 3.5 ng. per ml. for every cc of cancer, a level at least 10 times that observed for benign prostatic hyperplasia. Prostate specific antigen is useful as a preoperative marker because no patient with lymph node metastasis had serum levels of less than 10 ng. per ml. (4 times the upper limit of normal range). Of the patients with greater than 50 ng. per ml. two-thirds had microscopic lymph node metastasis and 90 per cent had seminal vesicle invasion. Serum prostatic acid phosphatase levels showed a significantly weaker correlation with cancer volume (r equals 0.51) and every other pathological parameter. Of the patients 73 per cent had serum prostatic acid phosphatase levels in the normal range (0 to 2.1 ng. per ml.), including 7 per cent who had pelvic lymph node metastasis. Postoperative prostate specific antigen values were available in 97 of 102 patients, with a mean and maximum followup of 12 and 38 months. No patient with pelvic lymph node metastasis achieved an undetectable prostate specific antigen level without adjunctive therapy (hormonal or radiation). No difference in preoperative or postoperative prostate specific antigen levels, cancer volume, seminal vesicle invasion or incidence of pelvic lymph node metastasis was seen between patients with no capsular penetration and those with minimal capsular penetration (1 cm. or less total linear extent of full thickness penetration), providing the first quantitative evidence that small amounts of capsular penetration may not be of biological or prognostic significance.

Serum PSA was related to prostate cancer 20 years ago. In the last 5 years serum PSA has only been related to benign prostatic hyperplasia. There is an urgent need for serum markers that reflect the size and grade of this ubiquitous cancer.

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.