W. Bedford Waters

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.

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7–28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vβ gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

ERECTILE DYSFUNCTION AFTER RADICAL PROSTATECTOMY: HEMODYNAMIC PROFILES AND THEIR CORRELATION WITH THE RECOVERY OF ERECTILE FUNCTION

PURPOSE Despite the advent of nerve sparing radical prostatectomy some men experience erectile dysfunction. Many of these men have vasculogenic erectile impairment in the form of arterial insufficiency or venous leakage. Recent data imply that early postoperative injection therapy may decrease the rate of erectile dysfunction. We defined hemodynamic patterns in patients who underwent bilateral nerve sparing radical prostatectomy to assess the chronology of venous leakage development and explore the correlation of hemodynamic profiles with the return of functional erection 12 months postoperatively. MATERIALS AND METHODS Patients with excellent preoperative erectile function who underwent bilateral nerve sparing surgery and had no pharmacological support for erectile dysfunction in the initial 12 months after surgery received vascular evaluation at presentation. Vascular evaluation involved cavernosometry or penile ultrasonography. Patients were then interviewed again at least 12 months postoperatively to assess the ability to achieve sexual intercourse. RESULTS Our study group comprised 96 men with a mean age plus or minus standard deviation of 54 +/- 12 years who met all inclusion criteria. All patients had pathologically proved organ confined disease. Mean time to the initial postoperative presentation was 6 +/- 5 months. Patients were divided into 4 groups according to the time of vascular studies postoperatively, namely less than 4 to 8, 9 to 12 and greater than 12 months. Normal vascular status, arterial insufficiency and venous leakage were diagnosed in 35%, 59% and 26% of the group, respectively. No difference in the incidence of arterial insufficiency was noted in the 4 time groups. Time postoperatively was significantly associated with the incidence of venous leakage (14% at less than 4 months and 35% at between 9 and 12). In regard to the correlation of the vascular diagnosis with the return to functional erection 47% of the normal, 31% of the arteriogenic and 9% of the venous leakage group achieved sexual intercourse 12 months postoperatively. CONCLUSIONS These data imply that the longer the duration of erectile dysfunction after radical prostatectomy, the greater the risk of venous leakage. Furthermore, it appears that the prognosis for the return of functional erection is worst when venous leakage is present.

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.

Aggressive Surgical Approach to Renal Cell Carcinoma: Review of 130 Cases

AbstractA retrospective analysis of 130 patients with renal cell carcinoma seen between 1957 and 1977 disclosed important diagnostic and pathologic factors relating to prognosis. Initial symptoms did not correlate with prognosis but a third of the patients had metastases when first seen by a physician. The classic triad of hematuria, flank pain and mass was present in only 4 per cent of the patients.Angiography demonstrated hypervascular tumors in 93 per cent of the patients. Hypovascularity on an angiogram correlated well with papillary renal cell carcinoma with improved prognosis. The renal vein was involved in 21 per cent of the patients and the inferior vena cava was involved in 4 per cent.Radical nephrectomy with or without lymph node dissection was the most common operation and heminephrectomy was performed in patients with a solitary kidney or hypoplastic contralateral kidney. Management of tumor thrombus in the renal vein or inferior vena cava required specialized operative techniques, including v...

The prevalence and nature of orgasmic dysfunction after radical prostatectomy.

Section Editor

Sexual Impotence: The Overlooked Complication of a Second Renal Transplant

The incidence of sexual impotence in 20 men who have received at least 2 kidney transplants was 65% compared to 10% after the first transplant. The importance was transient (2 to 4 months) in both affected men after the first transplant but permanent (2 to 10 years) in 6 men after the second operation. We attribute this increased percentage of impotence to the second end-to-end arterial anastomosis that requires division of the internal iliac arteries. We suggest that the second transplant be placed end-to-side into the common iliac artery.

PROSTATIC LEVELS OF FATTY ACIDS AND THE HISTOPATHOLOGY OF LOCALIZED PROSTATE CANCER

PURPOSE The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test. RESULTS The percent of total prostatic polyunsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha-Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega-3 and omega-3-to-omega-6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined. CONCLUSIONS These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans.

Urodynamic Evaluation of Prostatic Enlargements with Micturitional Vesicourethral Static Pressure Profiles

We studied 58 men with prostatism, who were between 58 and 75 years old, with micturitional vesicourethral static pressure profiles. The study consisted of recording static (lateral) pressures of successive segments of the posterior urethra during voiding, with synchronous monitoring of the vesical pressure activity. An abnormal pressure decrease across the supramontane urethra was considered to be a functional compromise to the prostatic urethra. The studies indicated that the degree of prostatic urethral obstruction was not related to the clinical and endoscopic assessment of prostatic enlargement. Three major patterns emerged from our studies: 1) moderate to severe prostatic enlargement with severe obstruction, 2) moderate to severe prostatic enlargement with minimal or no obstruction and 3) minimal prostatic enlargement with severe obstruction. Also, a good correlation became apparent between micturitional vesicourethral static pressure profilometry and uroflowmetry.