Edilberto I. Ramirez

The distribution of prostate specific antigen in men without clinical or pathological evidence of prostate cancer : relationship to gland volume and age

We estimated the in vivo prostate gland volume in 408 men (320 without clinical evidence of prostate cancer, and 88 with an abnormal digital rectal examination and/or transrectal prostate ultrasound and negative biopsies) using sequential step-section ultrasound analysis and correlated it to the serum prostate specific antigen (PSA) value. Of the men 331 (81.1%) had a PSA value of 4 ng./ml. or less. The PSA value was greater than 4 but less than or equal to 10 in 64 men (15.7%) and greater than 10 in 13 (3.2%). The men were subclassified by prostate gland volume at arbitrary break points. A total of 139 men (34.1%) had a gland of 25 cm.3 or less, 2.2% of whom had a PSA value of greater than 4. Further analysis revealed that the incidence of a PSA value greater than 4 increased as the prostate volume increased (18.4% for greater than 25 but less than or equal to 50, and 65.4% for greater than 50) and as age increased. We found a statistically significant association between prostate gland volume and patient age (p less than 0.00005) to the serum PSA concentration. The finding of a PSA value of greater than 10 was uncommon regardless of the prostate gland volume. Clinical implications of these results are discussed, and a statistical model to estimate the serum PSA by gland volume and patient age was constructed.

Tumor volume and prostate specific antigen : implications for early detection and defining a window of curability

PURPOSE We attempted to determine the relationship between tumor volume and extent of localized prostate cancer, as well as the interrelationships of tumor volume with prostate specific antigen (PSA) level, grade and stage. MATERIALS AND METHODS Serial whole mount sections from 128 patients who underwent radical prostatectomy were analyzed using a computer assisted volumetric program. Statistical evaluations were performed using logistic and simple regression analyses. RESULTS The median tumor volume for patients with organ confined disease was significantly lower than for those with extraprostatic extension (1.25 versus 2.94 cc, p < 0.001). A significant incidence (32%) of small volume cancers (0.51 to 1.5 cc) exhibited extraprostatic extension while that of extraprostatic disease increased to 66% for patients with tumor volumes greater than 1.5 cc (p < 0.001). Of men with clinically significant (greater than 0.5 cc, or Gleason score 7 or more) pathological stage B disease 31% had a serum PSA value of 4 ng./ml. or less. Multivariate regression analysis of tumor volume as a function of PSA, grade and stage demonstrated that log PSA had the strongest association with tumor volume. Goodness-of-fit analysis (coefficient of determination) revealed that only 40 to 50% of the PSA levels are explained by tumor volume. CONCLUSIONS These data suggest that the window of curability for prostate cancer decreases significantly once the tumor grows to a volume greater than 1.5 cc, and that grade and tumor volume are more significantly related to stage than PSA.

Prostate cancer staging: Correlation between ultrasound determined tumor contact length and pathologically confirmed extraprostatic extension

PURPOSE We determine whether a new parameter, the amount of tumor in contact with the fibromuscular rim (capsule) of the prostate, correlates with extraprostatic extension, and ascertain whether estimating the new parameter using transrectal ultrasonography can predict extraprostatic extension. MATERIALS AND METHODS We analyzed step sectioned prostatectomy specimens from 189 patients who had had positive peripheral zone biopsies. We measured the contact length, maximum length (mm.) of the portion of the peripheral zone cancer that was in contact with the fibromuscular rim, and determined the contact ratio from the quotient (%) of the contact length divided by the tumor circumference. We evaluated the correlation between the pathological and ultrasound measurements of these parameters, as well as the accuracy of these criteria for predicting microscopic extraprostatic extension. RESULTS Among the 189 cancers there was a significant difference (p <0.0001) between organ confined tumors and tumors with extraprostatic extension in contact length and contact ratio. There was a positive correlation (r = 0.691) between the contact lengths measured ultrasonically and histologically among 95 patients who had hypoechoic lesions associated with positive biopsies. A receiver operating characteristics curve of the ability of ultrasound estimated contact length to predict extraprostatic extension revealed the best cutoff value to be 23 mm. with 77% accuracy. Logistic regression analysis revealed that pathological contact length correlated better with extraprostatic extension than tumor volume, Gleason score, prostate specific antigen (PSA) level and pathological contact ratio. The best preoperative predictor of extraprostatic extension was the ultrasound contact length, followed by the contact ratio, PSA value, percentage of the biopsy specimen that was cancer and presence of perineural invasion in the biopsy specimen. Multiple logistic regression analysis revealed that the predictability of ultrasound contact length was improved by considering PSA value also. Probability plots for predicting extraprostatic extension were developed by combination of ultrasound contact length with PSA value. CONCLUSIONS The length of tumor contact with the fibromuscular rim is more significantly related to extraprostatic extension than tumor volume, PSA level and tumor grade. For hypoechoic cancers a new ultrasound staging criterion, contact length, has been defined. For men who are clinically candidates for radical prostatectomy and have peripheral zone hypoechoic cancers the combination of ultrasound contact length and PSA value is the best predictor of extraprostatic extension.

PROSTATE SPECIFIC ANTIGEN AND PATHOLOGICAL FEATURES OF PROSTATE CANCER IN BLACK AND WHITE PATIENTS: A COMPARATIVE STUDY BASED ON RADICAL PROSTATECTOMY SPECIMENS

PURPOSE We compared the relationship of pathological features and preoperative prostate specific antigen (PSA) levels of a consecutive series of black patients to a stage matched cohort of white patients treated during the same period. MATERIALS AND METHODS The radical prostatectomy specimens of 40 black patients were reviewed and tumor volume was determined. Histopathological features (stage, grade, zonal distribution of cancer foci), tumor volume and prostate weight were correlated to pretreatment serum PSA levels. These parameters were compared with those of 148 white patients matched by pathological stage. RESULTS Black patients exhibited a significantly higher incidence of seminal vesicle involvement (p=0.03) and cancers with a Gleason score of 8 or more (p=0.02), and a trend toward decreased pathologically organ confined, margin negative disease (40% black versus 53% white men, p=0.13). Although the incidences of multifocal cancer were virtually identical (90 and 82%) in the 2 groups, black patients exhibited a higher incidence of transition zone cancer foci (p <0.001). Mean prostate tumor volume, total gland weight and serum PSA level among black and white patients with pathological stage pT2-, pT2+ and pT3- cancer were not significantly different. However, with advancing pathological stage (pT3+ and pT3c) disease black patients had higher preoperative serum PSA levels on univariate and multivariate analyses despite similar total gland weight and tumor volume. CONCLUSIONS Black patients who underwent radical prostatectomy often exhibited adverse pathological features. Two novel findings were that the distribution of cancer foci within the prostate was significantly different between black and white patients, and that serum PSA levels in patients with locally advanced prostate cancer were higher in black than in white men, despite adjustment for known variables affecting PSA. These observations suggest that differences in the biology of prostate cancer between these 2 races may exist.

Comparative Analysis of Prostate Specific Antigen and its Indexes in the Detection of Prostate Cancer

PURPOSE Prostate specific antigen (PSA) density and age referenced PSA have been proposed in an attempt to improve the power of PSA in the detection of early prostate cancer. Reported results have been controversial and disappointing. Because the association of gland volume with PSA is stronger than that of age we developed a new index, volume referenced PSA, and compared it to PSA density and other indexes. MATERIALS AND METHODS Volume referenced PSA was developed from a control group of 408 men without clinical evidence of prostate cancer using a standardized Z score. A retrospective analysis was performed comparing PSA and all its indexes in 580 men who underwent prostate biopsy. In addition to overall analysis, PSA and its indexes were evaluated with receiver operating characteristic curves by age and volume subcategories. RESULTS Cancer was identified in 35% of the 580 men. The number of missed cancers using established thresholds significantly favored volume referenced PSA clinically and statistically compared to all other indexes but it was equivalent to PSA alone clinically. Age referenced PSA prevented more biopsies from being done than did volume referenced PSA (39% versus 31%) but resulted in the diagnosis of 48% fewer cancers. Receiver operating characteristic curve analysis demonstrated a significantly better performance for volume referenced PSA and PSA density compared to PSA alone and age referenced PSA. CONCLUSIONS Volume based PSA indexes are superior to PSA and age referenced PSA statistically. However, clinically volume referenced PSA is comparable to PSA, and both are superior to age referenced PSA and PSA density in the detection of prostate cancer.

Deoxyribonucleic acid flow cytometry and traditional pathologic variables in invasive penile carcinoma : Assessment of prognostic significance

OBJECTIVES The identification of reliable prognostic factors to guide the selection of patients at high risk of harboring subclinical metastases in penile cancer is important. We evaluated traditional pathologic variables and deoxyribonucleic acid (DNA) flow cytometry to determine the prognostic significance of these variables for the subsequent development of lymph node metastases. METHODS Clinical data and pathologic specimens were retrospectively reviewed from patients treated surgically at university-affiliated hospitals from 1958 to 1987. Pathologic analysis (grade, depth of invasion, and pathologic stage) and DNA flow cytometry were performed on specimens from 46 patients with invasive penile carcinoma and complete medical records. Pathologic variables were compared with DNA flow cytometry results in patients who never developed lymph node metastasis (32 patients, median follow-up 121 months) and in those who presented with or developed proved lymph node metastases (14 patients, median follow-up 18 months). RESULTS The distributions of diploid and nondiploid tumors were similar in patients with or without lymph node metastasis. In addition, there was no significant difference in the grade distributions of tumors with respect to lymph node status. Patients with positive nodes more commonly had tumors that invaded greater than 0.5 cm or that exhibited pathologic Stage T2 or greater (deep invasion). All 14 patients who presented with or subsequently developed metastasis had deep primary tumors. Thirteen of 36 patients with clinically negative nodes had superficially invasive tumors (pathologic Stage T1 and depth of invasion 0.5 cm or less), and none developed metastasis (median follow-up 124 months [range 58 to 240]). Tumor grade was significantly related to the likelihood of deep invasion but was not an independent prognostic factor for metastasis. CONCLUSIONS DNA flow cytometry does not add prognostic information to that obtained by pathologic assessment in patients with invasive penile carcinoma. The presence of pathologic Stage T2 or greater or depth of invasion greater than 0.5 cm defines a group of patients at high risk of inguinal node metastasis. A novel finding was that patients with minimally invasive lesions (0.5 cm or less) and no evidence of corporal invasion (pathologic Stage T1) have little risk of inguinal node metastasis. Close observation of reliable patients meeting these criteria may be a safe alternative to prophylactic lymphadenectomy.

Monoclonal prostate-specific antigen in untreated prostate cancer. Relationship to clinical stage and grade.

The authors evaluated 440 men with clinically staged and untreated prostate cancer with a monoclonal prostate‐specific antigen (PSA) assay. The serum PSA value correlated significantly with both the stage and grade of disease (P < 0.00005). The relationships between PSA and consecutive Stages A, B, C, and D2 (α = 0.15) and between progressive Gleasons scores 2 to 4, 5 to 7, and 8 to 10 (α = 0.15) were statistically significant. Also statistically significant was the correlation between serum PSA level and intracapsular versus extracapsular disease (P < 0.00005), although no one value can be used to differentiate reliably between patients in these two categories. The probability of clinically detectable metastasis (Stage D2) is 85% if the serum PSA level is greater than 30; however, 12% of patients without clinical evidence of metastases (Stages A, B, and C) have such a serum PSA value. Despite the statistically significant association between PSA and tumor differentiation and volume as reflected by tumor grade and clinical stage, this marker cannot be used to determine either for an individual patient.

Early detection program for prostate cancer: results and identification of high-risk patient population

Three hundred sixty-two men underwent transrectal ultrasound of the prostate (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen (PSA) determination as part of an early detection program for prostate cancer. Thirty-seven (10%) cancers were detected. DRE had the highest sensitivity and specificity, 89 percent and 84 percent, respectively. TRUS and PSA had comparable sensitivities (84% and 81%) and specificities (82% and 82%). The positive predictive values of DRE, TRUS, and PSA determination were 39 percent, 35 percent, and 33 percent, respectively. We found a cancer detection rate of 16 percent among patients with symptoms of bladder outlet obstruction and 5 percent in patients without these symptoms. The detection rate was 36 percent for physician-referred patients and 3 percent for self-referred patients. This suggests to us that at the present time the best utilization of medical resources to increase prostate cancer detection is to educate men to have annual medical evaluations by primary-care physicians who are encouraged to incorporate risk assessment and screening DRE as part of their routine practice. Any man with either abnormal findings on examination or increased risk should be referred to a urologist for further evaluation.

Diagnostic testing for prostate cancer detection: Less is best

The incidence of clinically organ-confined prostate cancer has markedly improved in programs designed to detect this disease by utilizing a combination of diagnostic modalities including digital rectal examination (DRE), transrectal ultrasonography (TRUS), and prostate-specific antigen (PSA). Biopsies were performed on 436 men who had abnormal findings on DRE, TRUS, or PSA. Overall, 39 percent of these men had histologic confirmation of prostate cancer. TRUS diagnosed more cancer (94%) than either DRE (80%) or PSA (89%), while the combination of TRUS and PSA diagnosed a similar number of cancers as the combination of DRE and PSA (100% vs 98%). The positive predictive value (PPV) of DRE and PSA combination was significantly better than that of TRUS and PSA (p = 0.01), but was not different from that of a combination of all three tests. DRE and PSA would have missed 4 cancers, but would have cost approximately 140 percent less than any program employing TRUS. Consequently, we recommend that the combination of DRE and PSA be used in primary early detection for prostate cancer and that TRUS be performed only when either or both DRE and PSA results are abnormal.

Original Articles: Bladder Cancer: Management of Transitional Cell Carcinoma Involving Von Brunn's Nests

We reviewed data collected from 371 patients with superficial transitional cell carcinoma of the bladder to determine whether carcinoma within von Brunns nests is a risk factor for cancer progression and an indication for radical cystectomy. Cystectomy was done in 20 of 73 patients (27%) with transitional cell carcinoma in von Brunns nests and in 42 of 298 patients (14%) without von Brunns nest involvement. There was no significant difference in the Kaplan-Meier crude and disease-specific survival between patients with and without transitional cell carcinoma in von Brunns nests, irrespective of whether radical cystectomy was performed initially. Of those patients with von Brunns nest involvement none who underwent cystectomy died of bladder carcinoma, while 3 (6%) managed conservatively died of bladder cancer. Of those patients without von Brunns nest involvement 1 (5%) managed with cystectomy and 9 (4%) managed conservatively died of bladder carcinoma. Furthermore, only 8 patients (15%) with and 29 (11%) without transitional cell carcinoma in von Brunns nests showed disease progression after initial conservative management. Based on this analysis, our conclusion is that transitional cell carcinoma within von Brunns nests is not a risk factor for disease progression or an absolute indication for radical cystectomy.