Have complication rates decreased after treatment for localized prostate cancer?

PURPOSE: The American Urological Association Prostate Cancer Clinical Guidelines Panel reviewed 12,501 publications on prostate cancer from 1955 to 1992 to determine whether the complication rates of external beam radiation therapy, interstitial radiotherapy and radical prostatectomy have decreased. MATERIALS AND METHODS: Complications reported in at least 6 series, study duration and sample sizes were extracted. Year specific study weighted mean patient ages and complication rates were computed. Regression analysis was performed of the study year on weighted mean patient age and complication rate. RESULTS: Study year had a significant effect on mean patient age and rate of the majority of complications examined. Data indicated a gradual increase in study patient age and a simultaneous decrease in complications from 1960 to 1990. CONCLUSIONS: Complication rates in the treatment of localized prostate cancer have decreased during the last 20 to 40 years. This decrease occurred despite evidence that the average age of treated patients had increased during the same period.

Prostate Cancer Clinical Guidelines Panel Summary report on the management of clinically localized prostate cancer. The American Urological Association.

PURPOSE: The American Urological Association convened the Prostate Cancer Clinical Guidelines Panel to analyze the literature regarding available methods for treating locally confined prostate cancer, and to make practice policy recommendations based on the treatment outcomes data insofar as the data permit. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles from 1966 to 1993 on stage T2 (B) prostate cancer and systematically analyzed outcomes data for radical prostatectomy, radiation therapy and surveillance as treatment alternatives. Outcomes considered most important were survival at 5, 10 and 15 years, progression at 5, 10 and 15 years, and treatment complications. RESULTS: The panel found the outcomes data inadequate for valid comparisons of treatments. Differences were too great among treatment series with regard to such significant characteristics as age, tumor grade and pelvic lymph node status. The panel elected to display, in tabular form and graphically, the ranges in outcomes data reported for each treatment alternative. CONCLUSIONS: In making its recommendations, the panel presented treatment alternatives as options, identifying the advantages and disadvantages of each, and recommended as a standard that patients with newly diagnosed, clinically localized prostate cancer should be informed of all commonly accepted treatment options.

Normal range prostate-specific antigen versus age-specific prostate-specific antigen in screening prostate adenocarcinoma.

OBJECTIVES: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men. METHODS: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values. RESULTS: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687). CONCLUSIONS: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older.

Several investigations have determined that the serum prostate specific antigen (PSA) concentration is dependent upon patient age and, as a result, reference ranges wider than 0.0 to 4.0 ng./ml. have been suggested for men 60 years old or older. To determine the clinical usefulness of the age-specific reference ranges--0.0 to 4.5 ng./ml. for men 60 to 69 years old and 0.0 to 6.5 ng./ml. for men 70 years old or older--the medical records of 2,988 men 60 years old or older who presented to a single urological practice were examined. All patients were evaluated with a serum PSA determination, digital rectal examination and transrectal ultrasound. A total of 1,686 prostate biopsies was performed (biopsy rate 56%) and 608 cancers were diagnosed (cancer detection rate 20%). By using the age-specific reference ranges as compared to the 0.0 to 4.0 ng./ml. reference range, the sensitivity of PSA for detecting early prostate cancer decreased by 9%, while the specificity and positive predictive value increased by 11% and 5%, respectively. If the age-specific reference ranges had been used 92 prostate biopsies (5.5%) performed could have been avoided, while 19 men in the study population (0.6%) would not have had prostate cancer diagnosed. Of the nondetected cancers 13 (67%) occurred in men 70 years old or older and 18 (95%) were small tumors of favorable pathological status unlikely to be of clinical consequence in these older men. These preliminary findings support the clinical usefulness of the wider age-specific reference ranges in men 60 years old or older. A prospective randomized clinical trial is currently underway to confirm the appropriateness of age-specific reference ranges compared to the reference range of 0.0 to 4.0 ng./ml.

Serum PSA adjusted for volume of transition zone (PSAT) is more accurate than PSA adjusted for total gland volume (PSAD) in detecting adenocarcinoma of the prostate.

OBJECTIVE: This study evaluates the accuracy of comparing serum prostate-specific (PSA) levels in the range between 4.1 ng/mL and 10.0 ng/mL (monoclonal) to the volume of the transition zone (TZ) of the prostate and total gland volume as a predictor of a positive biopsy. METHODS: Using sonographic voluming of the entire prostate and of the TZ, prostate-specific antigen density (PSAD) and prostate-specific antigen density of the TZ (PSAT) were calculated in 21 biopsy-positive patients and 38 biopsy-negative patients. Biopsy was directed at sonographically suspicious areas and did not include sextant biopsies. RESULTS: A statistically significant association was determined between a positive biopsy and gland volume, TZ volume, and PSAT. The association of a positive biopsy with PSA and PSAD was not statistically significant. CONCLUSIONS: PSAT is more accurate in predicting a positive biopsy than is PSAD for PSA levels between 4.1 ng/mL and 10.0 ng/mL.

Predictive value of prostate-specific antigen density for the presence of micrometastatic carcinoma of the prostate.

OBJECTIVE: To examine the efficacy of prostate-specific antigen (PSA) density (PSAD; serum PSA/prostate volume) as a predictor of clinical outcome of patients undergoing radical retropubic prostatectomy for clinically confined prostate cancer, and its ability to determine the presence of micrometastatic disease. METHODS: A retrospective analysis of patient outcome as reflected by surgical stage and postoperative PSA was performed with respect to PSAD as determined by preoperative PSA and pathologic prostate gland volume. The findings for 107 consecutive patients who underwent radical prostatectomy are reported. RESULTS: PSAD at low values was found to be 90 percent accurate in predicting operative success or absence of micrometastatic disease. PSAD at high values was shown to be 70 percent accurate in predicting failure. CONCLUSIONS: PSAD appears to be useful in selecting patients for radical prostatectomy and may be capable of identifying patients with micrometastatic disease.

Prostate-specific antigen and transrectal ultrasound of the prostate in detection of prostate cancer.

Detection of prostate cancer can be enhanced over the level historically obtained by digital rectal examination through the combined use of serum prostate-specific antigen and digital rectal examination, followed by transrectal ultrasonic examination of the prostate and ultrasonically guided biopsy if either of the initial studies is abnormal. Use of age-specific reference ranges for prostate-specific antigen results in greater sensitivity of this serum marker in patients below the age of 60 y and greater specificity in older patients.

Definition of the ideal tumor marker.

It is evident that the ideal tumor marker is not, nor should it be, a perfect tumor marker given the present level of our knowledge about prostate cancer. Further refinement of our information about prognosis and optimal treatment of this disease will ultimately lead to greater utility of many of the features of an ideal marker. On the other hand, the perfect tumor marker may become a moot issue if its development is overtaken by definitive information about prostate cancer etiology and prevention from the realm of molecular biology. Until that millennium is reached, we must continue to seek improvement in tumor markers that will permit us to take advantage of those features that are clinically useful at the current stage of our knowledge.

PSA density (PSAD). Role in patient evaluation and management.

Prostate Specific Antigen (PSA) is the most accurate serum marker for cancer of the prostate. However, sensitivity and specificity are suboptimal, especially at the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA levels, prostate specific antigen density (PSAD) provides unique information regarding the need for biopsy and the likelihood of prostate cancer. This article summarizes the utility of PSAD in diagnosing and treating prostate cancer.

Influence of patient age on the serum PSA concentration. An important clinical observation.

Although PSA is a most valuable tool for the practicing physician, it lacks sufficient sensitivity and specificity for detecting early prostate cancer to be the perfect tumor marker. The parameters PSAD and PSA velocity are useful attempts to make PSA a better tumor marker, but they likewise are not always reliable on an individual basis. There is now evidence from several investigations that the serum PSA concentration in healthy men without clinical evidence of prostate cancer increases with advancing age. This is primarily attributable to the concomitant increase in prostate size over the same time period. As a result, age-specific reference ranges have been determined and have the potential to make PSA a more sensitive tumor marker for men less than 60 years of age and a more specific tumor marker for men beyond 60 years of age. If one utilizes the age-specific reference ranges for serum PSA, it appears that PSAD can be eliminated as a parameter in the diagnostic evaluation of patients suspected of having prostate cancer. Thus, a new algorithm utilizing age-specific reference ranges has been developed.

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density.

Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is < or = 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is < or = 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1-10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important.2_

Prostate-specific antigen coordinated with digital rectal examination and transrectal ultrasonography in the detection of prostate cancer.

In a patient population, coordinated use of digital rectal examination and prostate-specific antigen can alert the physician as to the possible existence of prostate cancer. If both are used as first-line studies, abnormality of either can then direct the need for further study by transrectal ultrasonography and, in selected instances, prostatic biopsy. Such sequential use of these tests in a programmed manner results in an increased level of cancer detection as compared with use of the digital rectal examination alone.

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen.

Prostate specific antigen (PSA) is an extremely valuable tumor marker. However, its use in detection is limited by its low positive and negative predictive values. The ability of serum PSA to distinguish between benign and malignant prostatic conditions is particularly poor in the intermediate range of 4.1 and 10 ng./ml. by the Hybritech assay. We used transrectal ultrasound determined prostate volumes in a well characterized population of 533 men to form a serum PSA/prostate volume ratio called prostate specific antigen density (PSAD). The prevalence of cancer in the entire population was 18.4%. Discriminant analysis according to negative or positive outcome allowed for the construction of nomograms, which resulted in a PSAD defined cancer risk ranging from 3 to 100%. Predictive value nomograms created from PSAD may allow for a more individualized approach to evaluation of patients with intermediate levels of Hybritech serum PSA.

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Rectal examination and ultrasonography in the diagnosis of prostate cancer.

Most patients with prostate cancer have disease that has extended beyond the confines of the gland at the time of diagnosis. The effect of earlier detection on morbidity and death requires further study, as does assessment of prognostic factors and optimal therapy for individual patients. Recent reports indicate the utility of using prostate specific antigen and digital rectal examination as preliminary tests to identify patients in whom further study by prostate ultrasonography will improve detection rates. The algorithm presented may be a useful guide in sequencing detection approaches. The value of mass screening for prostate cancer by any existing means remains unproven.