Prostate Carcinoma Screening Research Articles

Generalists' Prudence May Lead to Better Outcomes

Markson et al 1 have provided evidence of slower adoption of therapeutic modalities by primary care providers compared with specialists, using zidovudine in patients with the acquired immunodeficiency syndrome as an example. They imply that such patterns of adoption represent inferior care by primary care providers. Another interpretation of their observations should be offered, however. Specialists frequently use the latest diagnostic and therapeutic modalities, in some cases prior to demonstration of superior efficacy. The result could be seen as reckless embracement of newer is better, and the result has often been hazardous to patients. Certainly after the results of the Concorde Trial, 2 prudent physicians should take pause at the suggestion that broadly supplying zidovudine to patients with the acquired immunodeficiency syndrome represents superior health care. Other examples of overenthusiastic adoption of new technology might include prostatic serum antigen screening for prostatic carcinoma and the widespread use of cholesterol-lowering

Il follow-up longitudinale del paziente sottoposto a screening per carcinoma prostatico: Follow-up of patients submitted to screening for prostate cancer

Early-stage prostate cancer is usually asymptomatic and therefore, in the past, has often gone undetected, unless diagnosed by a digital rectal examination. Recently, in order to improve the detection of early stage disease, new tests have been introduced, namely prostate specific antigen and transrectal ultrasound. Considerable debate exists not only about the usefulness of the screening but also about the routine use of these tests. In this article the features of these tests, single or in combination are discussed, and how to perform follow-up of the patient already submitted to screening for prostatic carcinoma.

Volume adjustment for intermediate prostate-specific antigen values in a screening population.

In a screening population of 812 men, between the ages of 55 and 77 years, and prostate-specific antigen (PSA) below 10.0 ng/ml (Hybritech), digital rectal examination (DRE) and transrectal ultrasonography of the prostate (TRUS) were performed. Seventeen prostate carcinomas were detected. Four methods of prostate volumetry were used to determine volume-adjusted PSA levels. These were PSA density for the total gland volume (PSAD), for the inner zone volume (PSAT) and population-specific excess PSA values. There was a significant difference between the benign and the malignant population for age, PSA, PSAD, PSAT and excess PSA values. The maximal discriminatory potential, analysed by the area under receiver ROC curve, was 0.90, reached for prolate spheroid determined excess PSA. For PSA alone this was 0.86. Volume-adjusted PSA values have no additional benefit beyond unadjusted values in screening for prostate carcinoma in this study.

Chest radiography in patients with early stage prostatic carcinoma. Effect on treatment planning and cost analysis.

An evaluation of the impact of routine preoperative chest radiographs was retrospectively undertaken in a pilot group of 292 patients with prostatic carcinoma who were part of a prospective study of prostate specific antigen screening for prostate carcinoma. Retrospective. Hospital-based outpatients. A cost-effectiveness model was used to assess the value of routine chest radiography in this patient population. Chest radiography findings were categorized into four groups based on follow-up and impact. Forty-three patients (15 percent) had a total of 45 positive findings on their chest radiographs. No patient had intrathoracic metastases from prostatic carcinoma. Only two patients (both with unsuspected second neoplasms) had findings that impacted on their treatment and one avoided retropubic radical prostatectomy. Total cost was $2,000 (based on Medicare reimbursement), or $14,000 (based on physician and hospital charges). Although benefit is small in terms of number of patients affected, clinical impact, in the two patients with significant findings, was great. Although cost-effectiveness cannot be confirmed on the basis of this series, further evaluation of its utility for this application should be undertaken.

Age-Specific Reference Ranges for Prostate-Specific Antigen

<h3>To the Editor.</h3> —In their recent article in<i>JAMA</i>, Oesterling et al¹describe a randomly chosen population of 537 asymptomatic men between 40 and 79 years of age who participated in a clinical examination including prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS), and TRUS-guided biopsies on indication. Only 88% of these men formed the study population, since 61 men (11%) did not complete the investigations and five men (1%) were found to have prostatic carcinoma. The data of Oesterling et al are compatible with those of the Rotterdam feasibility study of screening for prostate carcinoma in 548 men between 55 and 75 years of age, published by Kirkels et al.²Although the correlation of serum PSA concentration with age was only.²¹in the study by Kirkels et al, the correlation of prostatic volume with age and PSA concentration was the same as in the

Screening for Prostatic Carcinoma with Prostate Specific Antigen: Results of the Second Year

Prostate specific antigen (PSA) has been shown to be useful alone and in conjunction with other tests in the diagnosis of prostatic carcinoma. Previously, we demonstrated that a PSA level of greater than 4.0ng./ml. as the initial diagnostic test in a screening population results in a detection rate of 2.6 and positive predictive value of 30.5. In the present investigation we performed digital rectal examination and transrectal ultrasound as well as ultrasound guided biopsy in men who in the initial year of the screening study had a PSA level of less than 4.0ng./ml. but on evaluation 1 year later they had a 20% increase in the PSA level.A total of 701 subjects returned for year 2 of the protocol and 260 (37.1%) demonstrated more than a 20% increase in PSA value. Biopsy was performed in 82 men and carcinoma was detected in 14 (17.1%). Of the men with carcinoma 12 had a second year PSA level of less than 4.0ng./ml.Radical prostatectomy was performed in 8 patients, 7 of whom had organ confined disease or tumor penetrating the capsule with negative margins. We conclude that a 20% annual change in PSA level may identify men at significant risk for prostatic carcinoma and that patients so identified have favorable pathological stage.

Value of transrectal prostate ultrasonography pre-transurethral prostatectomy in screening for occult prostate carcinoma

A total of 311 patients who underwent consecutive transurethral resection of prostate (T URP) for obstructive voiding symptoms were reviewed. All patients had benign prostate glands by digital rectal examination. Results of preoperative ultrasound screening of the prostate in 65 of 311 patients showed 41 with nonmalignant prostate, but pathologic examination showed cancer in 11 and benign hyperplasia in 30. Of seven ultrasounds interpreted as suspicious for cancer, pathologic examination revealed benign hyperplasia in all seven. Of 17 patients with ultrasound interpretations consistent with prostate cancer, 14 had transrectal ultrasound-guided prostate biopsies prior to T URP. Biopsy specimens revealed benign hyperplasia without carcinoma in all 14 patients. Two of 17 patients refused biopsies, and 1 underwent TURP without biopsy for urinary retention and did have cancer. Sensitivity of prostate ultrasound in evaluation of occult prostate carcinoma in this group of patients was 8.3 percent and specificity was 56.6 percent. Our results indicate that transrectal prostate ultrasound performed on men with obstructive voiding symptoms and benign glands as evidenced by digital rectal palpation has little value in predicting the presence or absence of occult prostate cancer.

Screening for Prostatic Carcinoma with Prostate Specific Antigen

Prostate specific antigen (PSA), neutral serine protease secreted exclusively by prostatic epithelial cells, has a number of applications in the management of men with prostatic carcinoma. While it is widely recognized that elevated PSA correlates with the presence of carcinoma, little data exist regarding the use of PSA as the initial test in the early detection of prostatic cancer. We measured serum PSA levels in men older than 50 years and performed digital rectal examination and ultrasound guided prostate biopsy of those who had a PSA level of greater than 4.0 ng./ml.A total of 1,249 men entered the protocol, of whom 187 (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and ultrasound guided biopsy were performed at our facility in 105 patients (56.2%). A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml. Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands demonstrating only asymmetry on digital rectal examination, and 3 men had carcinoma despite normal digital rectal examination and no hypoechoic peripheral zone lesion detected on ultrasound. Of the 32 patients 30 had clinically localized carcinoma but 7 of the 16 undergoing radical prostatectomy had pathological upstaging. We conclude that PSA represents an important adjunct to digital rectal examination for the early detection of prostatic carcinoma. The efficacy of this or any other early detection test to decrease prostate cancer mortality necessitates the results of prospectively randomized clinical trials.

Neuroendocrine differentiation in human prostatic carcinoma

Endocrine-paracrine (APUD, neuroendocrine) cells are located in the prostatic ductal and acinar epithelium. These cells are of the open and closed type and have dendritic processes. There is a wide range of secretory granule morphology presumably indicating a variety of different cell “type.” Secretory immunoreactive peptides include serotonin, calcitonin (and related peptides), somatostatin, bombesin-like, thyroid-stimulating hormone-like (beta chain), and alpha-glycoprotein chain-like. These cells may function by endocrine, paracrine, neurocrine, and lumencrine mechanisms and play an important regulatory role both during growth and differentiation of the prostate as well as in the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma is a frequent occurrence and manifests itself in several forms, including (1) small cell carcinoma, (2) carcinoid and carcinoid-like tumors, and (3) conventional adenocarcinoma with focal neuroendocrine differentiation. This latter pattern is the most common, and there is evidence that all or nearly all prostatic adenocarcinomas show at least some focal neuroendocrine differentiation. A review of the world's literature on this topic is included. Neuroendocrine differentiation generally portends a poorer prognosis but may also correlate directly with the grade. There is some evidence to suggest that neoplastic cells with neuroendocrine differentiation are resistant to hormonal therapy. Europic and ectopic hormone production may allow screening for prostatic carcinoma and/or monitoring for recurrence of prostatic carcinomas. Finally, the more basic implications of endocrine-paracrine cells and neuroendocrine differentiation are speculated on in reference to prostatic carcinogenesis and autocrine/paracrine tumor growth factor activity.

Mass screening for prostatic carcinoma and therapeutic options

In western countries, prostatic carcinoma is the most frequent neoplasia in the male sex after pulmonary neoplasia. Its early diagnosis is very important. The authors report the results of a screening for prostatic carcinoma effected in some municipalities of the district of Parma (Italy); 28 prostatic carcinomas were diagnosed (1.2% of the examined patients). Twelve patients were submitted to radical nerve-sparing prostatectomy according to Walsh. In all of them, PSA values decreased to values &lt; 1 ngr/ml, confirming the radicality of the operation and few complications occurred. The conclusion of the authors is that nowadays timely radical prostatectomy is the only “definitive” treatment of prostatic carcinoma, allowing a better quality of life, however long it is.

The Value of Screening for Prostatic Carcinoma: A Commentary

Can routine digital rectal examinations, transrectal ultrasound studies, and prostate-specific antigen determinations reduce deaths from prostatic carcinoma? The evidence is that the benefits of early diagnosis and treatment are at least neutralized by the limited reliability and high monetary and human costs of the test and by the lack of proof that treatment is effective for those tumors detected. One must conclude that universal screening is not now warranted and will await demonstration of effectiveness by controlled studies.

前立腺集団検診による前立腺癌および前立腺肥大症の実態調査

We conducted mass screenings for prostate diseases on male subjects over fifty years of age in three separate areas in Hokkaido. Prostate carcinoma and benign prostatic hypertrophy were searched in the 1,764 participants. Histopathologically proven prostate carcinoma was found in twenty-two (1.25%) of the 1,764 participants. This frequency of carcinoma was higher than any other carcinoma found in the mass screenings for gastric, uterine, breast and lung carcinoma in Hokkaido. Of the 22 prostate carcinomas found, 68% were in the early stage (stage B). This stage distribution was clearly distinct from that of prostate carcinoma found on the hospital visit, most of which had already progressed to an advanced stage. These results indicate that mass screening for prostate carcinoma on greater than or equal to 50 year old-male subjects is efficient in finding carcinoma of all stages but, in particular, carcinoma of early stage, when compared with mass screening for other carcinomas. BPH, defined as a moderately or markedly enlarged prostate on rectal palpation, was found in 10% of the participants. Questionnaire on subjective symptoms of voiding disturbance in the participants has confirmed that these symptoms, mainly elicited by BPH, become manifested in fifties and more frequent with age. Of thirteen patients with prostate carcinoma who received both rectal examination and prostate-related markers measurement in serum at the time of mass screening, three without induration of the prostate were diagnosed as having carcinoma from an abnormal value of the serum markers. This result suggests that the marker(s) is one of the useful screening tests for detecting carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for carcinoma of the prostate: Authors' reply

Screening for carcinoma of the prostate: Authors' reply

Prostate Specific Antigen—a Screening Test for Prostatic Cancer?

A series of 287 patients referred by their family doctors with symptoms of bladder outflow obstruction were asked to attend the hospital for "pre-clinic" screening for carcinoma of prostate (CaP). Blood samples were collected from 211 patients and analysed for serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Thirty-six patients had a serum PSA greater than 10 micrograms/l and 7 had PAP levels greater than 5 iu/l. In no instance was the PAP elevated without an associated increase in PSA concentration. Patients with raised markers underwent further investigations which included prostatic biopsy and/or resection; 17 patients were proved to have carcinoma of the prostate, 9 of whom had distant metastases. The specificity of PSA for detecting prostate cancer in this study was 90% with a sensitivity of 89.5%, in contrast to values for PAP of 100% and 36.8%. The routine use of PAP as a marker for prostatic cancer should be abandoned. The use of PSA as a screening test in a group of patients with prostatism appears justified, but with a positive predictive value of only 47%, its use in a mass unselected screening programme is not recommended.

Serum acid phosphatase activity in the diagnosis of carcinoma of the prostate

In an attempt to evaluate the role of serum acid phosphatase estimation in the diagnosis of prostatic carcinoma, computer files of both the Clinical Chemistry and Histopathology Divisions of the Institute of Medical and Veterinary Science and the case records of the Royal Adelaide Hospital were reviewed over the period February 1974 to February 1976. The case selection was as follows: All cases with a histological finding of carcinoma of the prostate and/or an elevated serum acid phosphatase level were included. This number totalled 311. Excluded were cases where histology or biochemistry was not performed or could be compromised. The final number of patients for our study=79. The predictive values and the true positive ratios were determined and the results are summarized in the table.Acid phosphatase elevationTotal aloneTartrate labile aloneBothHistological diagnosis:Carcinoma9120Non carcinoma1721Predictive value (of a positive test for carcinoma)0.35 (9/26)0.33 (1/3)0.95 (20/21)True positive ratio0.18 (9/55)0.02 (1/55)0.36 (20/55) There was little correlation between activity and the histological grading of malignancy or evidence of local or metastatic extension. The highest true positive ratio occurred when the total activity was elevated (0.53) but this had a poor predictive value (0.62). The best predictive value occurred when both fractions were elevated (0.95) but this had a lower true positive ratio (0.36). It is concluded that the determination of serum acid phosphatase activity is of definite value in certain clinical situations. However, the test will have little value in the screening for prostatic carcinoma until its sensitivity and specificity are improved.