Pathology review in an early prostate cancer detection program: Results from the american cancer society-national prostate cancer detection project

Biopsy materials obtained in the American Cancer Society National Prostate Cancer Detection Project were reviewed at the Central Pathology Laboratory at the Armed Forces Institute of Pathology. Of 265 cases submitted, 177 were diagnosed as prostatic carcinoma, 7 as prostatic intraepithelial neoplasia (PIN), 13 as atypical glands or atypical hyperplasia, and the remaining 68 were benign hyperplasias. Irrespective of the means of detection or the grading system used (Gleason or WHO-Mostofi), a large majority of the cancers were detected as low-grade tumors. Of 27 cases of PIN reported, 20 were associated with cancer, leaving 7 cases with the sole diagnosis of PIN. These data may indicate the increased use of prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS) in the United States is shifting the spectrum of prostate cancer pathology toward early low-grade tumors. © 1995 Wiley-Liss, Inc.     

Digital rectal examination in the early detection of prostate cancer

Screening using digital rectal examination improves the clinical stage distribution of prostate cancer and prolongs survival. Unfortunately, digital rectal examination may not be sensitive enough to detect the small-volume tumors that are most amenable to cure. In several studies, approximately 50 per cent of cancers detected through screening had already spread beyond the prostate. Regardless, the key to demonstrating overall benefit from screening is a diminished disease-specific mortality rate. To date, this has not been shown. Lower mortality rates from prostate cancer can be demonstrated only through a randomized study comparing screened and unscreened populations. Such a study, which has recently been approved and funded by the National Institutes of Health, will require 10 to 15 years to complete. Until that time, the value of screening for prostate cancer by digital rectal examination or any other method will be unknown. Beyond a lack of proved benefit, screening for prostate cancer may be harmful because of the variable natural history of the disease and the morbidity and mortality rates associated with treatment. There exists a large population of patients with pathologically detectable prostate cancer who will never have clinical disease. The detection of some of these tumors may expose those patients to the risks of unnecessary treatment. Large-scale prostate cancer screening studies may ultimately be shown to be advantageous. The sooner this occurs, the earlier aggressive screening can be advocated, similar to screening for breast cancer. However, the temptation to embark on such screening programs without first demonstrating clear benefit should be resisted.     

Evaluation of transrectal ultrasound in the early detection of prostate cancer

To determine the ability of transrectal ultrasound to detect early localized prostate cancer, unsuspected (nonpalpable) cancer in the contralateral lobe of patients undergoing radical prostatectomy for clinically localized disease was evaluated. A total of 59 patients with palpable prostate cancer clinically confined to 1 lobe underwent transrectal ultrasound before radical prostatectomy and step-sectioning of the radical prostatectomy specimen. Transrectal ultrasound was performed with 5 or 7 MHz. real-time transrectal units. Pathological findings in these 59 cases revealed no tumor in the contralateral lobe in 34 (58%) and the presence of unsuspected tumor in 25 (42%). Transrectal ultrasound detected 13 of 25 unsuspected cancers for a sensitivity of 52%. Of 34 patients with no contralateral lobe lesion transrectal ultrasound was correct in 23 for a specificity of 68%. The positive and negative predictive values for transrectal ultrasound in this study group were 54 and 66%, respectively. There was no significant difference in the pathological size of the clinically suspected and clinically unsuspected cancers as measured by average largest dimension, and transrectal ultrasound sensitivity did not correlate with the size of the cancer. Based on careful sonopathological analysis, transrectal ultrasound may not be a good method to detect clinically unsuspected prostate cancer and the false positive rate would appear to be high.     

Metabolomic signatures of aggressive prostate cancer

BACKGROUND

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings.

METHODS

A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer‐free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography–mass spectrometry and ultrahigh performance liquid chromatography–tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement.

RESULTS

Prostate tumors had significantly altered metabolite profiles compared to cancer‐free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate‐specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness‐associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5‐year recurrence (AUROC from 0.53 to 0.64).

CONCLUSIONS

These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Prostate 73: 1547–1560, 2013 © 2013 Wiley Periodicals, Inc.     

Innovative concepts in early cancer detection and staging of localized prostate cancer

Prostate cancer is the most common malignancy in males. Men aged 50 years and older are recommended to undergo an annual digital rectal examination (DRE) and determination of prostate-specific antigen (PSA) in serum for early detection. Fortunately, disease-specific mortality continues to decline as a result of advances in screening, staging, and patient awareness. However, about 30% of men with a clinically organ-confined disease show evidence of extracapsular extension or seminal vesicle invasion on pathological analysis. Consequently, there is a need for more accurate diagnostic tools for planning tailored treatment. A variety of modern imaging techniques has been implemented in an attempt to obtain more precise staging, thereby allowing for more detailed counseling, and instituting optimum therapy. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients.     

Transrectal ultrasonography for the early detection and staging of prostate cancer

Relatively recent changes and improvements in equipment have vastly increased image resolution for transrectal ultrasonography of the prostate. The expanded use of transrectal ultrasonography has greatly furthered knowledge of prostate zonal anatomy and permitted clinical evaluation of internal prostate architecture. The technique is operator dependent, as the quality of the results is related directly to that person's knowledge and experience. The significant majority of prostate cancers originate from the peripheral zone. Palpable stage B nodules characteristically have a hypoechoic appearance. There is disagreement about the tumor characteristics that cause hypoechogenicity, but large tumors may obscure the normal prostate anatomy and appear isoechoic because of the lack of contrast with surrounding prostate tissue. The transition zone of the prostate is the origin of benign prostatic hyperplasia and almost 20 per cent of prostate cancers. These tumors probably correspond to most stage A lesions. Transrectal ultrasonography is less accurate in identifying transition zone tumors because of the mixed echogenicity of the transition zone, interference from prostatic calculi or calcified corpora amylacea, and poorer image resolution in this area. Studies evaluating the use of transrectal ultrasonography for early detection of prostate cancer generally have shown a twofold increase in the detection rate compared with digital rectal examination. However, the decreased morbidity and expense of transrectal prostate biopsy using an automatic gun device have increased the frequency of biopsy in ultrasound-examined patients compared with those historically evaluated by digital rectal examination. The increased detection rate may in part be a function of the increased use of biopsies, independent of other factors. Transrectal ultrasonography rarely detects cancer in patient with normal digital rectal examination and a normal serum prostate-specific antigen level. Transrectal ultrasonography may be capable of identifying early capsular penetration or seminal vesicle invasion in some patients with known prostate cancer. However, its superiority to digital rectal examination for this purpose has not been demonstrated unequivocally. Ultrasonography does allow directed biopsies of the seminal vesicles or other suspect areas, and this may be helpful in staging the disease. The use of transrectal ultrasonography in prostate cancer has evolved rapidly, and changes in technology antiquate reports within a few years.(ABSTRACT TRUNCATED AT 400 WORDS)     

The significance of early detection for prostate cancer in mass screening

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.     

The role of prostate-specific antigen velocity in prostate cancer early detection

Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.     

Transrectal ultrasound in early detection of clinical stage A prostate cancer

A group of 40 select men were studied to assess the value of transrectal ultrasound in the early detection of prostate cancer. All had a benign digital rectal examination and had either irritative lower tract symptoms, hematospermia, microhematuria, or an elevated acid phosphatase. Of the men, 28 had an abnormal ultrasound and underwent a directed prostate needle biopsy to assess the ability to detect clinical Stager A cancer. Eleven men (40%) were found to have cancer, all having hypoechoic lesions. The remainder were found to have benign prostatic hypertrophy (BPH) with hyperechoic lesions predominating (88%). Our results suggest that transrectal ultrasound is a useful and sensitive method for the detection of prostate tumors not clinically evident on digital rectal examination in select patients.     

Comparative evaluation of various prostate specific antigen ratios for the early detection of prostate cancer

OBJECTIVE: To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer. PATIENTS AND METHODS: The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated. RESULTS: Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios. CONCLUSIONS: The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.