SLAP lesions: a retrospective multicenter study

This study was performed to assess the relationship between the level and extent of prostatic capsular invasion (PCI) by cancer and the clinical and pathological features and prognosis of early-stage prostate cancer. We conducted a retrospective analysis of the clinical (age, stage, grade, prostate specific antigen [PSA] level) and pathological (tumor volume, stage, grade, surgical margins) features of 688 patients treated with radical prostatectomy to determine the pathological features and probability of recurrence associated with various levels of PCI. Radical prostatectomy specimens were serially sectioned and examined by whole-mount technique. Progression-free probabilities (PFP) after radical prostatectomy were determined by Kaplan-Meier and Cox proportional hazards regression analysis. Progression was defined as a rising serum PSA < or = 0.4 ng/mL or clinical evidence of recurrent cancer. Increasing clinical stage, Gleason grade in the biopsy specimen, and pretreatment serum PSA levels were each associated with increasing levels of PCI (P < .001). In the radical prostatectomy specimen, increasing levels of PCI were significantly associated with increasing tumor volume (P < .001), Gleason grade (P < .0001), seminal vesicle involvement (SVI, P < .001) and lymph node metastases (+LN, P < .001). None of 138 patients without capsular invasion had SVI or lymph node metastases (+LN), and all remained free of progression, even though some had large volume (up to 6.26 cm3) or poorly differentiated (Gleason sum up to 8) cancers. Invasion into the capsule (n = 271) was occasionally associated with SVI (6%) or +LN (3%) and a significantly (log-rank test) lower PFP of 87% at 5 years. Focal and extensive extraprostatic extension (EPE) were associated with progressively increased risk of SVI and +LN and lower PFP (73% and 42%, respectively). In a multivariate analysis, the level of PCI was an independent prognostic factor (P < .001). There is a strong association between the level of invasion of cancer into or through the prostatic capsule and the volume, grade, pathological stage, and rate of recurrence after radical prostatectomy. Prostate cancer does not appear to metastasize in the absence of invasion into the capsule regardless of the volume or grade of the intracapsular tumor. Subclassification of patients according to the levels of PCI provides valuable prognostic information.     

The role of PSA in the radiotherapy of prostate cancer

Pretreatment prostate-specific antigen (PSA) level is the single most important prognostic factor for patients undergoing radiotherapy for clinically localized prostate cancer. When combined with Gleason score and T-stage, pretreatment PSA enhances our ability to accurately predict pathologic stage. Patients with pretreatment PSA levels > 10 ng/mL are at high risk for biochemical failure when treated with conventional radiation alone. A PSA nadir of > 1 ng/mL and a post-treatment PSA > 1.5 ng/mL are associated with a high risk of biochemical failure. Postoperative radiotherapy delivered while the tumor burden is low (eg, PSA < 1 ng/mL) predicts a favorable outcome. Many of these conclusions about the usefulness of pretreatment PSA are based on the assumption that PSA can be used as a surrogate end point for disease-free and overall survival from prostate cancer. However, this assumption still remains to be validated by phase III trials.     

Serum antibodies to diphtheria-tetanus-pertussis vaccine components in Argentine children

In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage T1c). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-T1c tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-T1c tumors with preoperative PSA levels below 4 ng/ml, and non-T1c tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization mode, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics. T1c tumors are clinically significant tumors. The overall low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.     

Cosmetics, skin care products, and the dermatologic surgeon. Postsurgical selection of cleansing products

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or premalignant lesions, including hyperplasia and intraepithelial neoplasia. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy. Glomeruloid features may be a useful diagnostic clue for malignancy, particularly in some challenging needle biopsy specimens. This pattern of growth is usually seen in high-grade adenocarcinoma, often with extraprostatic extension. Further investigations are required to determine its independent predictive value and correlation with stage and Gleason score.     

Outcome based staging for clinically localized adenocarcinoma of the prostate

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.     

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.     

A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer

PURPOSE: A multivariate analysis is used to determine the predictive value of pretreatment clinical indicators on pathologic features associated with local failure after radical prostatectomy in patients with prostate cancer. METHODS AND MATERIALS: A retrospective review of the pathologic findings of 235 patients with adenocarcinoma of the prostate treated between 1990 and 1993 with a radical retropubic prostatectomy was performed. The preoperative clinical data including the serum prostate specific antigen, clinical stage, Gleason sum, and endorectal magnetic resonance scan findings are used to identify patients prior to definitive treatment who would be at high risk for having pathologic features associated with local failure at radical prostatectomy. Outcome prediction curves are constructed from a logistic regression multivariate analysis displaying the probability of pathologic involvement of the seminal vesicle, extracapsular disease, or positive surgical margins as a function of the preoperative prostate specific antigen and Gleason sum for the cases when the endorectal magnetic resonance scan is positive, negative, or not included in the multivariate analysis. RESULTS: Factors identified on multivariate analysis as significant predictors of seminal vesicle invasion include endorectal magnetic resonance scan findings (p < 0.0001), and preoperative prostate specific antigen (p = 0.017). Endorectal magnetic resonance scan findings (p = 0.0016), preoperative prostate specific antigen (p = 0.0002), and Gleason sum (p < 0.0001) were significant predictors of extracapsular extension and preoperative prostate specific antigen (p < 0.0001) and Gleason sum (p = 0.03) were significant predictors of disease extending to the margins of resection. Clinical stage was not a significant predictor (p > 0.05) of pathologic features associated with local failure on multivariate analysis. As a single modality, endorectal surface coil magnetic resonance imaging was accurate 93%, 69%, and 72% of the time for predicting seminal vesicle invasion, transcapsular disease, and final pathologic stage, respectively. Failure to recognize microscopic penetration of the capsule found at the time of pathologic evaluation in a prostate gland with a grossly intact capsule accounts for the majority (70%) of the staging inaccuracies. CONCLUSIONS: The use of the endorectal surface coil magnetic resonance scan findings in conjunction with both the serum prostate specific antigen and Gleason sum improves the clinical accuracy of predicting those patients at high risk for clinically unsuspected extraprostatic disease. In particular, for the subgroup of patients with moderately elevated prostate specific antigen (> 10-20 ng/mL) and intermediate grade clinically organ confined prostate cancer [Gleason sum: 5-7] where the specificity of these tests to predict for occult extraprostatic disease is suboptimal, the additional information obtained from the endorectal coil magnetic resonance scan allows the physician to definitively subgroup these patients into low and high risk for seminal vesicle invasion or transcapsular disease.     

Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate

BACKGROUND: The accumulation of chromogranin A (Chr A) and cathepsin D (Cath D) gene products may be important in prostate carcinoma progression. This study assessed whether the levels of immunoreactivity for Chr A and Cath D are better predictors of disease specific survival than conventional pathologic parameters of the primary tumor such as Gleason score, capsular penetration, seminal vesicle invasion, and percent tumor in the specimen for patients with clinically localized prostate carcinoma managed by radical prostatectomy. METHODS: Seventy-one patients with modified Jewett clinical stages A1 to B2 adenocarcinoma of the prostate underwent a radical prostatectomy after a negative metastatic workup. No neoadjuvant or adjuvant treatments were given and all disease recurrences and causes of death were recorded. Analysis of prostatectomy specimens was undertaken to determine the conventional pathologic parameters of the primary tumor and Chr A and Cath D immunohistochemical staining. Univariate and multivariate analyses were performed to determine the independent contributions of Chr A and Cath D in predicting survival. RESULTS: On univariate analysis Chr A was the only variable that reached statistical significance for disease specific survival (P = 0.035). Cath D nearly reached significance with a P value of 0.079 for disease specific survival. On multivariate analysis, the only independent factor predicting disease specific survival was the Chr A staining score (P < 0.05). In patients with unequivocal foci of Chr A immunoreactivity, the 14-year disease specific survival was 50% compared with 68% for patients lacking such foci. CONCLUSIONS: The level of Chr A immunohistochemical staining is a strong predictor of disease specific survival and is superior to standard pathologic prognostic factors. Such findings lay the groundwork for future prospective study of the utility of such markers on biopsy specimens to predict patient outcome.     

Improved lung function and quality of life following increased elastic recoil after lung volume reduction surgery in emphysema

OBJECTIVES: To investigate whether tumor volume, an important prognostic factor in prostate cancer, could be estimated from the amount of cancer in multiple core biopsies. METHODS: In 80 men, transrectal ultrasound-guided biopsies were taken from focal lesions detected by ultrasound and 8 to 10 standardized positions, including sextant biopsies (apex, midmedial, base) and midlateral and transition zone biopsies. The cancer length in the biopsies was measured. After radical prostatectomy, the prostates were totally embedded, whole-mounted, and tumor volume was measured planimetrically. RESULTS: The tumor volume correlated significantly with the total cancer length of all biopsies (r = 0.56) and of the sextant biopsies (r = 0.39). It was found that midlateral and transition zone biopsies provided independent information when included in a multiple regression model with tumor volume as the dependent variable and the sextant biopsies as explanatory variables. All men (n = 6) with less than 3 mm cancer length in only one positive biopsy and a Gleason score less than 7 had a tumor volume less than 1 mL. Nine of 10 men with less than 7 mm of cancer in one positive biopsy and Gleason score less than 7 had tumors smaller than 1 mL. Sextant biopsies did not reliably predict cancer volumes less than 1 mL. CONCLUSIONS: The cancer yield of 8 to 10 biopsies correlated better with the volume of prostate cancer than sextant biopsies. This extended biopsy protocol could be used to predict cancers of less than 1 mL in volume.     

Results of transition zone biopsy in black and white men with suspected prostate cancer

OBJECTIVES: To determine whether biopsy-detectable transition zone tumors are more common in black than in white men with suspected Stage T1c and T2 prostate cancer. METHODS: We performed a prospective study of transition zone prostate biopsy (TZ biopsy) in 1 78 black and 261 white men who had not undergone previous prostate biopsy and in 61 black and 65 white men who had undergone one benign sextant peripheral zone prostate biopsy (PZ biopsy). RESULTS: The mean age of the 239 black and 326 white study patients was 68.6+/-7.4 and 67.2+/-7.2 years, respectively (P = 0.02), the mean prostate-specific antigen (PSA) was 8.4+/-7.4 and 6.4+/-5.4 ng/mL, respectively (P = 0.003), and the mean PSA density was 0.20+/-0.23 and 0.16+/-0.16 ng/mL/mL, respectively (P = 0.006). Overall, cancer was diagnosed by TZ biopsy only in 7 black men (3%) and in no white men (0%) (P = 0.003). However, cancer detection with a TZ biopsy only was not significantly different in the black and white men when controlled for age, PSA, or PSA density (P>0.90). A TZ biopsy only detected cancer in 1% of patients who had not undergone prior PZ biopsy and in 2% of patients who had undergone prior PZ biopsy. Of the seven cancers detected with TZ biopsy, six (86%) had a Gleason score of 2 to 6. CONCLUSIONS: Prostate cancer detection with a TZ biopsy only is not common and when controlled for confounding variables is the same in black and white men. The preferential use of TZ biopsies in black men is not warranted, and the low diagnostic yield argues against routine use of the biopsy technique in men of either race.     

Clinical studies on the prognostic factors in prostate cancer

To evaluate the prognostic factors and the outcome of treatment, a retrospective study was done on 141 patients with prostate cancer who were newly diagnosed at Kitano Hospital between January 1985 and November 1996. In recent years, the number of patients and the ratio of low stage cancer have increased. The overall 5-year crude survival rate was 49.9%. The 5-year crude survival rate for clinical stage A, B, C and D was 67%, 70%, 62% and 30% respectively. The overall 5-year disease-specific survival rate was 65.6%. The 5-year disease-specific survival rate for clinical stage A, B, C and D was 100%, 89%, 72% and 42%, respectively. By univariate analysis, clinical stage, Gleason score, prostate specific antigen (PSA) level, and patient age were prognostic factors for disease-specific survival of prostate cancer. According to Cox's regression analysis by the stepwise forward regression method, clinical stage and Gleason score were selected as more valuable prognostic factors than PSA level, patient age, comorbidity, and initial treatment. In Gleason score 2 to 8, the prognosis became significantly worse as clinical stage advanced, but in Gleason score 9 and 10 the prognosis was poor regardless of clinical stage.     

Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth

BACKGROUND: Cervical lymph node metastasis has a major influence on survival in oral cancer. However, the factors influencing its occurrence are uncertain. Our aim was to improve the prognostic efficiency of the histologic assessment of the primary tumor in predicting metastasis in an individual patient. METHODS: The relationship between selected clinical and histologic features of the primary tumor of tongue/floor of the mouth and the actual metastatic status was investigated in 45 patients. Invasive cell grading was supplemented by histologic measurements of tumor size and assessments of vascular and perineural invasion. RESULTS: Ten histologic features showed significant differences in relation to metastasis. A logistic regression model with two predictor variables (total histologic malignancy score and vascular invasion) classified correctly 39 (87%) of the 45 cases. CONCLUSIONS: Histologic assessment of tumor size and malignancy grade are useful in predicting metastasis. Vascular and perineural invasion are important predictors and should be included in multifactorial malignancy grading schemes. Application of the prognostic index to the biopsy specimen would aid in treatment planning.     

Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy: a decision analysis

Indications for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy have not been established. Criteria to predict lymph node metastases were derived from the preoperative evaluations of 164 prostate cancer patients undergoing pelvic lymphadenectomy. Decision analysis was used to determine which criteria would be optimal indicators for laparoscopic pelvic lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal examination suggesting uncontained tumor, which was the best indication for laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If either parameter was met, the sensitivity for identifying patients with pelvic lymph node metastases was 88 percent and the positive predictive value was 42 percent. When both were met, the sensitivity fell to 47 percent but the positive predictive value increased to 67 percent. A combination of Gleason biopsy score and PSA was the best criterion that was independent of transrectal ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6 had a sensitivity of 71 percent and positive predictive value of 48 percent for identifying patients with pelvic lymph node metastases. In selecting patients for laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy, criteria with a positive predictive value greater than 39 percent maximize the utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph node metastases that would otherwise be undetected by prostatectomy alone. The sensitivity of selection criteria, therefore, should be increased, as long as the positive predictive value remains above 20 percent.     

Surgical control of clinically localized prostate carcinoma is equivalent in African-American and white males

BACKGROUND: Few studies have compared the outcome of radical prostatectomy between African-American males (AAM) and white males, and the results of the few studies that have are conflicting. Therefore, the authors examined the impact of radical surgery on localized prostate carcinoma in both patient populations, and assessed whether stratification by pathologic extent of local disease would yield an equivalent outcome. METHODS: Prostate specific antigen (PSA) failure and carcinoma-associated death rates were assessed in 1319 patients (115 AAM and 1204 white males), 872 of whom had a pretreatment serum PSA level taken. The percent of prostate involved by tumor, tumor wet weight, and DNA ploidy status were available in 755, 522, and 638 patients, respectively. RESULTS: AAM were diagnosed at an earlier age than white males (62.8 years vs. 65.4 years; P = 0.0001). The distribution of pathologic extent of local disease was similar in both races, and AAM had a statistically higher rate of tumors with a Gleason sum of 7-10 at surgery than white males (64% vs. 46%). Race did not play a role in the outcome of patients with organ-confined or specimen-confined tumors. However, in patients with positive surgical margins, the median time to PSA failure and the median carcinoma-associated survival were less in AAM compared with white males. Tumor volume was significantly larger in AAM compared with white males. After multivariate adjustment for the pathologic extent of local disease, tumor grade at surgery, preoperative PSA, tumor volume, and age, African-American race was not a significant prognostic indicator for carcinoma-associated death and PSA failure (P = 0.17 and 0.14, respectively). CONCLUSIONS: The outcome of radical prostatectomy was similar in both racial groups, although AAM with positive surgical margins tended to fail earlier than white males, suggesting greater biologic aggressiveness of residual disease. Because local extent of disease impacts on PSA failure and survival, and because the disease appears to present earlier in AAM, the AAM population may benefit from early detection programs.     

The predictive value of race as a clinical prognostic factor among patients with clinically localized prostate cancer: a multivariate analysis of positive surgical margins

OBJECTIVES: Several investigators have reported that African-American men with clinically localized prostate cancer have poorer survival than do white men. In addition, prostate cancer in African-American men is commonly diagnosed at a more advanced stage of disease. Is race or ethnicity predictive of outcome of clinically localized prostate cancer? It has been reported that the presence of positive surgical margins significantly influences time to progression independently of other prognostic factors. Therefore, we have elected to conduct a multivariate analysis of clinical factors including race as potential predictors of positive surgical margin outcome. METHODS: We studied 369 consecutive men (120 African-American and 249 white) who had radical prostatectomies at a single institution. Comparisons by race of Gleason score, stage, presence of positive surgical margins, and mean preoperative prostate-specific antigen (PSA) level were carried out. RESULTS: Our data demonstrate that African-American men have more pathologically locally advanced prostate cancer than do white American men: 69% among blacks compared with 57% among whites. However, the difference in rate of positive surgical margins between blacks and whites is statistically significant: 58% among blacks versus 40% among whites (P = 0.002). Four factors were predictive of positive surgical margins: preoperative PSA level, race, clinical stage, and Gleason score. CONCLUSIONS: We have demonstrated that race is an independent predictor of positive surgical margins among patients with clinically localized prostate cancer and should be included in treatment decisions. In addition, the risk of positive surgical margins increases noticeably when PSA is greater than 10 ng/mL.     

Repeat transrectal ultrasound-guided prostate biopsy: a strategy to improve the reliability of needle biopsy grading in patients with well-differentiated prostate cancer

OBJECTIVES: Gleason grade from prostate needle biopsy (PNB) specimens is important in guiding therapeutic decision making in patients with localized prostate cancer. Recent data from our institution suggest a significant discordance between Gleason grading from PNB versus the actual pathologic grade at radical prostatectomy (RRP). Of most concern is that a substantial proportion of patients with Gleason score of 6 or less from PNB actually have Gleason score of 7 or more at RRP. Under classic measurement theory, one useful way to improve the reliability of an inherently unreliable test is to repeat it. We investigated this strategy in an effort to reduce undergrading errors. METHODS: The control group of patients (n = 51) from our neoadjuvant androgen deprivation protocol was used as the test (two-biopsy) group in this study. These patients underwent two separate PNBs before RRP. We used the highest Gleason score from the two biopsies in these patients and compared the error rates with a concurrent group of patients treated at our institution (n = 226) who had only one set (single-biopsy group) of prostate biopsies. All pathologic slides were reviewed at our institution. Any PNB grade of 6 or less that was scored as 7 or more on final pathology was considered significant. RESULTS: Mean age, prostate-specific antigen levels, and stage distribution were not significantly different between these two groups. In the single-biopsy group, 165 patients had PNB Gleason score of 6 or less. Of these patients, 63 (38%) had final pathologic grade of 7 or more. In the two-biopsy group, 37 patients had PNB Gleason score of 6 or less. Of these patients, only 7 (19%) had final pathologic grade of 7 or more (P = 0.04). CONCLUSIONS: Prostate rebiopsy minimizes the inherent unreliability of PNB derived grade and should be considered for patients in whom watchful waiting or nomogram-based therapy has been selected.     

Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate specific antigen based screening

PURPOSE: Many small (less than 0.5 cc), well differentiated, organ-confined prostate carcinomas remain clinically undetected during the life of the patient and are identified only at postmortem examination. Thus, these cancers are often called latent or autopsy cancers. There is concern that serum prostate specific antigen (PSA) based screening may preferentially detect these cancers. There are limited prospective data concerning the pathological features of carcinomas of the prostate detected in a screening program. We determined if prostatic carcinomas detected via PSA based screening resembled autopsy cancers. MATERIALS AND METHODS: We assessed the pathological features of carcinomas in 100 consecutive, completely embedded radical prostatectomy specimens from men whose cancer was detected in a PSA based screening program. The tumors were evaluated for pathological stage, surgical margin status, Gleason histological grade and intraglandular tumor extent (morphometrically quantified as percentage carcinoma and tumor volume). RESULTS: Of 100 carcinomas 68 (68%) were larger than 0.5 cc in volume (mean 1.7, range 0.1 to 10.7). Mean amount of carcinoma in the surgical specimen was 10.3% (range 0.1 to 41.6). Of the 100 carcinomas 94 had a Gleason score of 5 to 8 (mean 5.7) and only 6 (6%) were well differentiated (Gleason score of 4 or less). Locally advanced disease was noted in 41 cases (41%) as judged by the presence of extracapsular carcinoma and/or cancerous surgical margins. CONCLUSIONS: We concluded that the pathological features of most prostatic carcinomas detected via PSA based screening do not resemble those of autopsy cancers, and that most prostatic cancers detected in screening programs are likely to be clinically important.     

Reduced space hidden Markov model training

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.