Michael T. Macfarlane

Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men

&NA; To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom‐E or Tandem‐R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 &mgr;g./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 &mgr;g./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 &mgr;g./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves.

A prospective clinical trial of prostate cancer screening was conducted at 6 university centers including 6,630 men 50 years old or older who underwent a serum prostate specific antigen (PSA) determination and digital rectal examination. Biopsies were performed if the PSA level was greater than 4.0 ng./ml. (Hybritech Tandem assay) or digital rectal examination was suspicious for cancer. We evaluated the effect on biopsy rate and cancer detection if the cutoff value was shifted from 4.0 to age-specific reference ranges recommended in the literature. In men 50 to 59 years old with normal digital rectal examination findings a decrease from 4.0 to 3.5 ng./ml. would have resulted in a 45% increase in the number of biopsies (39 of 87) and a projected 15% increase in cancer detection. An increase from 4.0 to 4.5 ng./ml. in men 60 to 69 years old would result in 15% fewer biopsies (35 of 238) and would miss 8% of the organ confined tumors (2 of 25). Increasing the cutoff to 6.5 ng./ml. in men 70 years old or older would result in 44% fewer biopsies (70 of 159) and would miss 47% of the organ confined cancers (7 of 15). The number of biopsies performed for each cancer detected with a PSA level of greater than 4.0 ng./ml. remains constant across age groupings, which suggests that the cutoff of 4.0 ng./ml. does not need to be altered in the older men, since it is apparently unaffected by the simultaneously increasing prevalence of benign prostatic hyperplasia and cancer with age. We conclude that a serum PSA concentration of 4.0 ng./ml. should be used as a general guideline for biopsy in all age groups.

Comparison of Prostate Specific Antigen Concentration Versus Prostate Specific Antigen Density in the Early Detection of Prostate Cancer: Receiver Operating Characteristic Curves

We present the results of a prospective multicenter clinical trial of nearly 5,000 men in which prostate specific antigen (PSA) density was compared to the serum PSA concentration alone for early detection of prostate cancer. All men were evaluated with PSA and digital rectal examination. If PSA was elevated (greater than 4 ng./ml., Hybritech Tandem assay) or digital rectal examination was suspicious, transrectal ultrasound guided biopsies were recommended. Prostate volume was estimated by transrectal ultrasound measurements using a prolate ellipse volume calculation and PSA density was calculated by dividing serum PSA concentration by gland volume. Using a PSA density cutoff of 0.15 as recommended in the literature enhanced specificity but at the cost of missing half of the tumors. Of the organ confined neoplasms 47% were detected by a PSA of greater than 4.0 ng./ml. but they were missed by a PSA density of more than 0.15. PSA density may not be predictive for cancer because accurate estimation of transrectal ultrasound volume is difficult (r = 0.61 for estimated transrectal ultrasound volume versus pathological prostate weight). However, a relationship does exist among transrectal ultrasound volume, PSA and positive predictive value for cancer. PSA concentrations of less than 4.0 ng./ml. did not indicate a need for biopsy (positive predictive value 12 to 17%) unless the digital rectal examination findings were suspicious for cancer. A high percentage of patients with a PSA of more than 10 ng./ml. had cancer (30 to 75%), regardless of gland size. Patients with intermediate PSA concentrations (4.1 to 9.9 ng./ml.) and a gland size of 50 cc or less had a 35 to 51% positive predictive value, while those with intermediate PSA concentrations and a large gland (more than 50 cc) had a 15% positive predictive value. We conclude that in men with a PSA level of 4.1 to 9.9 ng./ml., and normal digital rectal examination and transrectal ultrasound findings, the use of a PSA density cutoff of more than 0.15 for biopsy results in half of the tumors being missed. Thus, we recommend that men in this group undergo biopsy based upon serum PSA concentration rather than PSA density.

EFFECT OF PATIENT AGE ON EARLY DETECTION OF PROSTATE CANCER WITH SERUM PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION *

This study was designed to determine the effects of age by decade on the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men aged fifty and over. A prospective multicenter clinical trial was conducted at six university centers. All 6,630 male volunteers underwent a serum PSA (Hybritech, Tandem) determination and DRE. Quadrant biopsies of the prostate were performed if PSA was > 4 ng/mL or DRE suspicious. A total of 1,167 biopsies were performed, and 264 cancers were detected. The cancer detection rate increased from 3 percent in men aged fifty to fifty-nine to 14 percent in men eighty years or older (p < 0.0001). PSA detected significantly more of the total cancers than DRE at all age ranges (p < 0.05). The positive predictive values (PPV) for PSA were 32 percent (50-59 years), 30 percent (60-69 years), 34 percent (70-79 years), and 38 percent (80+ years). The corresponding PPVs for DRE were 17 percent, 21 percent, 25 percent, and 38 percent. Eighteen percent of the cancers were detected solely by DRE, whereas 45 percent of cancers were detected solely by PSA. Thus, the use of both tests in combination provided the highest rate of detection in all age groups. One hundred-sixty patients underwent radical prostatectomy and pathologic staging. Cancer was organ-confined in 74 percent (25/34) of men aged fifty to fifty-nine, 76 percent (65/86) of men aged sixty to sixty-nine, and 60 percent (24/40) of men aged seventy or over (chi 2, < 70 vs. > or = 70, p < 0.05). Early detection programs yield a lower, yet still substantial, cancer detection rate in younger men, and there is a greater likelihood for detection of organ-confined disease in this age range. Younger men have the longest projected life expectancy and, therefore, the most to gain from early prostate cancer detection.

Accuracy of Digital Rectal Examination and Transrectal Ultrasonography in Localizing Prostate Cancer

Not all prostate cancers are sonographically hypoechoic or palpable on digital rectal examination, and suspicious areas on transrectal prostatic ultrasonography or digital rectal examination often are not cancer. We present quadrant biopsy results from a multicenter prostate cancer screening study in which men were evaluated with prostate specific antigen (PSA) and digital rectal examination. If the PSA level was elevated (greater than 4.0 ng./ml., Hybritech Tandem assay) or digital rectal examination was suspicious quadrant biopsies were performed. Biopsy specimens were labeled separately, and histological findings were correlated by quadrant with the findings on ultrasonography and digital rectal examination. Of the 6,630 subjects enrolled into the study 16% were biopsied. Of 1,002 quadrants that were suspicious on digital rectal examination 110 (11%) had cancer, while 308 of 418 quadrants containing cancer (74%) were not suspicious on digital rectal examination. Of 855 quadrants that were sonographically suspicious 153 (18%) had cancer, while 282 of 435 quadrants containing cancer (65%) were not sonographically suspicious. Of 225 patients with cancer 137 (61%) would have been missed if only the exact site of the palpable induration had been biopsied. Of 251 patients with cancer 131 (52%) would have been missed if only the exact site of the hypoechoic lesion had been biopsied. We conclude that digital rectal examination and transrectal ultrasonography have limited accuracy in identifying and localizing prostate cancer. Our study emphasizes the importance of obtaining systematic biopsies if the PSA level is elevated, even in the absence of digital rectal examination or ultrasound anomalies.

Neoadjuvant Hormonal Deprivation in Patients with Locally Advanced Prostate Cancer

A total of 22 patients with locally advanced prostate cancer (stage B2 to C) was entered into a protocol for 3 months of preoperative hormonal deprivation. Of the patients 8 were judged to have clinical stage B2 and 14 to have stage C disease. The protocol regimen consisted of daily administration of flutamide (250 mg. orally 3 times per day) and leuprolide injection (7.5 mg. intramuscularly) every month. Patients with objective evidence of downstaging by prostate specific antigen (PSA) levels and transrectal ultrasound were offered surgical therapy. Of the 22 patients 20 have completed the protocol and are evaluable, and 2 of them did not show significant downstaging and elected radiotherapy. Preoperative hormonal therapy produced an average 33% downsizing of the prostate gland as determined by transrectal ultrasound volumetrics. Decreases in serum PSA values were demonstrated from a pre-hormonal average of 30 micrograms./l. (range 0.7 to 97.7) to an average of 0.53 micrograms./l. (range 0.2 to 5.7) after hormonal therapy. Of the 18 patients who underwent an operation after demonstrating significant downsizing 7 had pathologically confirmed stage B disease, 7 had stage C cancer and 4 had positive pelvic lymph nodes. Of the 8 clinical stage B2 cancer patients 3 had pathological stage B2 disease following the protocol. Of the 12 clinical stage C cancer patients 3 had pathological stage B disease, 4 had positive pelvic lymph nodes and the remainder had pathological stage C cancer. Thus, only 3 of 20 patients (15%) demonstrated pathological downstaging from the clinical stage. Downsizing the prostate volume and PSA changes with hormonal therapy were not predictive of patient outcome either alone or in combination. Preoperative hormonal therapy did not appear to facilitate the surgical procedure. Patients completing neoadjuvant hormonal therapy had an average estimated blood loss of 1,238 ml. and an average operating time of 183 minutes. A group of 20 consecutive patients with stage B2 prostate cancer who underwent radical prostatectomy without preoperative hormone therapy had an average estimated blood loss of 1,296 ml. and an average operating time of 171 minutes.

Detection of local recurrence after radical prostatectomy by prostate specific antigen and transrectal ultrasound

Twenty patients with detectable levels of prostate specific antigen (PSA) after radical prostatectomy with no identifiable distant metastases were evaluated for local recurrence by digital rectal examination and transrectal ultrasound combined with biopsies. Of the patients 9 (45%) were found to have histological evidence of local recurrence at the initial assessment. All 4 patients with an abnormal digital rectal examination had recurrent disease. Transrectal ultrasound displayed abnormalities in 12 of the 20 patients, 7 of whom had positive biopsies. Random biopsies of the vesicourethral junction were performed in 8 patients who had negative ultrasound findings and an unremarkable digital rectal examination, of whom 2 had histological documentation of local recurrence. Complications occurred in 1 patient (5%) who presented with clot retention. We conclude that PSA is an excellent tool for identification of recurrent disease after radical prostatectomy, and transrectal ultrasound guided biopsy is a useful diagnostic approach in patients suspected of local failure, especially when the digital rectal examination is unremarkable.

Pregnancy in Women with Bladder Exstrophy

AbstractLittle is known about pregnancies in women with bladder exstrophy. Of 28 women with bladder exstrophy who were evaluated 7 became pregnant and 5 delivered successfully. Problems seen during pregnancy, the long-term effects and the need for early, informed counseling by the urologist are discussed.

Long-Term Followup After Exstrophy Closure: Late Improvement and Good Quality of Life

Now that we have observed the growth and development of 17 of our anatomically reconstructed exstrophy patients through 20 or more years of followup, we are convinced that reconstruction should be the preferred primary treatment. Most of these patients are healthy, attractive, well educated adults and have achieved emotional maturity and stability, despite their many problems. Anatomical reconstruction also has considerable advantages over other current treatments for exstrophy that were not apparent initially.

PREOPERATIVE ENDOSCOPIC DIAGNOSIS OF FIBROEPITHELIAL POLYP OF THE RENAL PELVIS : A CASE REPORT AND REVIEW OF THE LITERATURE

Benign fibroepithelial polyps of the renal pelvis are rare, with only 9 cases described previously in the literature. We report an additional case and suggest how nephrectomy may be avoided.