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D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 127 records · Page 7Linked to original sources
PubMed1999

Overdiagnosis of prostatic adenocarcinoma.

A wide variety of histopathologic mimics of prostatic adenocarcinoma have been recently described, which may cause overdiagnosis of malignancy. To our knowledge, the frequency and causes of overdiagnosis of prostate cancer have not been previously examined. Two pathologists evaluated the Mayo Clinic experience with small foci of stage T1a cancer diagnosed between 1960 and 1970 in an effort to identify cases that were overdiagnosed as cancer. Only cases with available diagnostic slides and blocks were re-evaluated, and immunohistochemical studies were obtained in select cases to confirm the amended diagnoses. Follow-up was obtained in all cases from patient medical records. We identified a total of 31 patients who were overdiagnosed with prostatic carcinoma from among a series of 150 cases initially diagnosed as well-differentiated stage T1a cancer (21% incidence). Patients ranged in age from 42 to 85 years, and the weight of the transurethral resections varied from 6 to 90 g. Findings misinterpreted as cancer included atypical adenomatous hyperplasia (8 cases), basal cell hyperplasia (8), atrophy (5), sclerosing adenosis (3), high-grade prostatic intraepithelial neoplasia (3), xanthogranulomatous prostatitis (2), florid cribriform hyperplasia (1), and post-atrophic hyperplasia (1). None of the patients received additional treatment for prostatic disease. Mean follow-up was 10.8 years; 14 patients were alive with no evidence of disease, 14 died of intercurrent disease without recurrent prostatic disease, and the status of 3 was unknown. We conclude that misinterpretation of prostate cancer in transurethral resection specimens results from overdiagnosis of small microscopic foci of hyperplasia, atrophy, prostatic intraepithelial neoplasia, and granulomatous inflammation. The incidence of overdiagnosis three decades ago was 21% of small foci in transurethral resections, usually resulting from the presence of undescribed pathological entities. Long-term follow-up revealed no evidence of recurrent prostatic disease.

Adenocarcinoma↗
PubMed1999

Prostate-specific antigen and other serum markers: current concepts from the World Health Organization Second International Consultation on Prostate Cancer.

Serum prostate-specific antigen is credited with dramatic advances in the early detection, screening, and management of men with prostatic carcinoma. There has been more than a twofold increase in the number of men diagnosed during the last decade, and prostate cancer has emerged as the most common non-skin cancer and the second leading cause of cancer death in men. This report summarizes the history and current status of prostate-specific antigen and other serum markers, incorporating consensus opinions from the Second International Consultation on Prostate Cancer held in Paris in June 1999.

Age Factors↗
PubMed1999

Predictive factors in prostate cancer: current concepts from the 1999 College of American Pathologists Conference on Solid Tumor Prognostic Factors and the 1999 World Health Organization Second International Consultation on Prostate Cancer.

Many clinically important predictive factors in prostate cancer are derived from light microscopic examination of tissue specimens by the pathologist. Two separate international consensus conferences held in 1999 addressed the contemporary status of such prognostic factors, sponsored by the College of American Pathologists (CAP) and the World Health Organization (WHO). Both conferences concluded that the following factors are recommended for routine use based on evidence from multiple published trials: TNM stage, histological grade using the Gleason system, surgical margin status, and serum prostate-specific antigen concentration. The WHO conference additionally recommended use of WHO nuclear grade, location of cancer within the prostate, and pathological effects of treatment. Other factors were categorized as promising or of unproven utility, including a wide variety of histopathologic and genetic markers. Standards are needed for analysis and quantitation of methods of tissue analysis, particularly for immunohistochemical studies and genotypic studies. This report describes the recommendations and conclusions of these two conferences.

Apoptosis↗
PubMed1999

Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans.

Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United States, is the second leading cause of cancer-related deaths of males in this country. Because of the poor success rate in the treatment of PCA, an intervention at an early stage may reduce the progression of small carcinoma to large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts are needed to establish mechanism-based approaches to develop: (a) the markers for early detection of the disease as well as toward monitoring the efficacy of treatment(s); and (b) novel chemopreventive strategies against PCA. Using unique samples of pair-matched benign and cancer tissue obtained from the same PCA patient, we showed that ornithine decarboxylase (ODC) activity is significantly (P < 0.001) elevated in PCA (1142 +/- 100; mean +/- SE) than in paired benign tissue (427 +/- 51; mean +/- SE). The immunoblot analysis also showed a significant elevation in the protein expression of ODC in the PCA tissues as compared with the paired benign tissue. Furthermore, our data showed that the ODC activity in the prostatic fluid obtained by a digital rectal massage from the patients with PCA (3847 +/- 162; mean +/- SE) was significantly higher than in the patients with benign prostatic hyperplasia (2742 +/- 167; mean +/- SE) or normal individuals (1244 +/- 67; mean +/- SE). This observation might be of significance because the prostatic fluid could be obtained noninvasively by digital rectal massage. We suggest that ODC could serve as a target for early detection of human PCA as well as for monitoring the efficacy of treatment(s). The development of ODC as a target for novel chemopreventive strategies against PCA is an intriguing possibility.

Biomarkers↗
PubMed1999

Steam heat with an EDTA buffer and protease digestion optimizes immunohistochemical expression of basal cell-specific antikeratin 34betaE12 to discriminate cancer in prostatic epithelium.

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer. Results were judged by the percentage of cells staining and by staining intensity. In benign epithelium, steam-EDTA + protease significantly increased the percentage of immunoreactive cells (from 74 to 93%) and the intensity of staining (from 2.1 to 3.0 on a scale of 0-3+) by comparison with protease alone (all P<.001). In high-grade prostatic intraepithelial neoplasia, the percentage of cells staining increased from 55 to 73% and intensity increased from 1.7 to 2.8 (both P<.001). Steam-EDTA + protease also minimized variability in results between cases, with essentially no background stromal staining. Cancer was negative in all of our cases by both methods. We conclude that steam-EDTA + protease significantly enhances basal cell immunoreactivity compared with protease treatment alone in noncancerous prostatic epithelium. This helps to prevent misinterpretation of histologic mimics of cancer, such as atrophic acini and high-grade prostatic intraepithelial neoplasia, that result from false-negative staining.

Antibodies, Monoclonal↗
PubMed1998

Prostate cancer microvessels: a novel method for three-dimensional reconstruction and analysis.

BACKGROUND: Studies of prostate cancer microvessels to date have relied on routine two-dimensional images from histologic tissue sections, and there have been no previous reports of three-dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two-dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated. METHODS: We developed a novel method to visualize and analyze prostate microvessels in three dimensions from serially-sectioned prostate specimens, including tissue preparation, reconstruction of serial histologic sections into 3D volumes, extraction of vessels from this data set, and calculation of geometric characteristics. Eleven regions of benign and cancer tissue were studied and compared in an effort to validate our methodology. RESULTS: Microvessels and glandular elements from benign and malignant tissue were visualized together in three dimensions. In the 3D visualizations, microvessels associated with cancer were seen to have more arbitrary pathways, increased tortuosity, and a more casual relationship with glandular elements than microvessels associated with benign tissue. A quantitative measure, the volume length density, discriminated between benign tissue and cancer better than simple microvessel density in this exploratory study. CONCLUSIONS: Microvessels in prostate cancer have a more homogeneous distribution and greater tortuosity than those in benign tissue. Volume length density of microvessels shows promise as a 3D marker in prostate cancer.

Adenocarcinoma↗
PubMed1998

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

BACKGROUND: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring. One such potential marker is prostate specific membrane antigen (PSMA). METHODS: A review was conducted to identify reports concerning evaluation of diagnostic applications of PSMA. RESULTS: PSMA is a membrane-bound glycoprotein that is highly restricted to the prostate. Immunohistochemical findings indicate that PSMA is a marker of epithelial cells of the prostate. This expression is increased in association with prostate carcinoma, particularly in hormone-refractory disease. Given its membrane-bound character, PSMA has been exploited as a marker for tumor detection by immunoscintiscanning with the 111In-labeled anti-PSMA monoclonal antibody 7E11.C5. Increased concentrations of 7E11.C5-reactive antigen are present in the serum of prostate carcinoma patients compared with healthy individuals; also, hematogenous circulating prostate carcinoma cells are detectable with reverse transcriptase-polymerase chain reaction analysis with primers specific for PSMA. New monoclonal antibodies specific for extracellular portions of the PSMA molecule currently are being utilized in applied studies. CONCLUSIONS: PSMA is a widely used marker for prostate epithelial cells. Its up-regulation in association with cancer, particularly in advanced cancer, is ideal for application as a prognostic marker. A variety of promising clinical applications utilizing PSMA have been or are being developed. In the future, these promise to have an important impact on cancer diagnosis and patient treatment.

Antigens, Surface↗
PubMed1998

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy.

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.

Aged↗
PubMed1998

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma.

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.

Aged↗
PubMed1998

Malignant lymphoma involving the prostate: report of 62 cases.

BACKGROUND: Malignant lymphoma involving the prostate is rare, and to the authors' knowledge the factors determining patient outcome have not been studied in a large series. METHODS: The authors evaluated the clinical and pathologic findings in 60 cases of non-Hodgkin's lymphoma and 2 cases of Hodgkin's lymphoma involving the prostate. A variety of clinical and histologic findings were considered as factors predictive of patient outcome. RESULTS: Lymphoma tended to occur in elderly men, with a mean age at diagnosis of 62 years (range, 5-89 years), although 6 patients were age < 40 years (ages 5, 19, 30, 32, 38, and 38 years, respectively). Clinical signs and symptoms were due to lower urinary tract obstruction. Twenty-two patients (35%) presented with primary extranodal lymphoma of the prostate with a variety of histologic subtypes, including small lymphocytic (4 patients); follicular center cell, diffuse, small cell (2 patients); follicular center cell, Grade 1 (according to the revised European-American classification (small cleaved) (1 patient); Grade 2 (mixed) (1 patient); diffuse large B-cell (12 patients); and high grade B-cell lymphoma, Burkitt-like (2 patients). At the time of presentation, none of these patients had hepatosplenomegaly, inguinal lymphadenopathy, or an abnormal complete blood count. Thirty other patients (48%) with previously documented lymphoma at other sites developed prostatic involvement; these secondary prostatic lymphomas displayed a variety of subtypes, including small lymphocytic (8 patients, all with concomitant leukemia); follicular center cell lymphoma, diffuse, small cell (2 patients); follicular center, Grade 1 (small cell) (1 patient); follicular center, Grade 2 (1 patient); diffuse large B-cell (11 patients); peripheral T-cell lymphoma (2 patients); high grade B-cell lymphoma, Burkitt-like (1 patient); Burkitt's lymphoma (1 patient); Hodgkin's lymphoma (nodular sclerosing [1 patient] and mixed cellularity [1 patient]); and unknown (1 patient). Ten cases were not classifiable as primary or secondary lymphomas. Twenty-five patients died of malignant lymphoma, 14 died of unknown or other causes, 18 patients were alive 12-20 months after diagnosis (8 primary and 10 secondary tumors; 3 had persistent lymphoma; all treated since 1981), and 5 were lost to follow-up. Lymphoma specific survival was 64% at 1 year (95% confidence interval [CI], 51-80%), 50% at 2 years (95% CI, 36-68%), 33% at 5 years, 33% at 10 years, and 16% at 15 years. There was no difference in median survival after diagnosis of prostatic involvement between primary and secondary lymphoma (23 months vs. 28 months, respectively) or among histologic types. CONCLUSIONS: Although malignant lymphoma involving the prostate is rare, it should be considered in the differential diagnosis of lower urinary tract obstruction, particularly in patients with a previous history of lymphoma.

Adult↗
PubMed1998

High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. METHODS: Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. RESULTS: High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. CONCLUSIONS: High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.

Adenocarcinoma↗
PubMed1998

Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases.

BACKGROUND: Prostate specific membrane antigen (PSM) is a membrane-bound antigen that is highly specific for benign and malignant prostate epithelial cells. Its expression in high grade prostatic intraepithelial neoplasia (PIN) has not been compared with that in prostate carcinoma. METHODS: The authors performed an immunohistochemical study of representative sections from 184 radical prostatectomies from previously untreated patients with pathologic stage T2N0M0 adenocarcinoma treated at the Mayo Clinic between 1987 and 1991. Affinity-purified monoclonal antibody 7E11-5.3 directed against PSM was employed at a concentration of 20 microg/mL overnight. For comparison, serial sections in each case were stained with prostate specific antigen (PSA). Staining for all antibodies was performed using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in increments of 10%. Cox proportional hazards models were used to identify the risk of carcinoma recurrence according to the number of immunoreactive PIN or cancer cells for PSM and PSA; the date of radical prostatectomy was used as the starting time, and serum PSA (biochemical) failure or clinical failure was the event. PSA biochemical failure was defined as serum PSA > 0.2 ng/mL at least 30 days after surgery. RESULTS: Intense cytoplasmic immunoreactivity for PSM was observed in the benign and neoplastic epithelial cells in all cases (100% of cases staining). The number of cells staining was lower in benign epithelium and PIN than in adenocarcinoma (69.5+/-17.3% [range, 20-90%] vs. 77.9+/-13.2% [range, 30-100%] vs. 80.2+/-13.7% [range, 30-100%], respectively). With rare exceptions, basal cells were negative, and there was no immunoreactivity of the prostate stroma, urothelium, or vasculature. Adenocarcinoma gave the most intense and extensive staining, and the highest grades of adenocarcinoma (Gleason primary patterns 4 and 5) showed staining in virtually every cell; there was greater heterogeneity of staining in lower grades of adenocarcinoma. By contrast, PSA immunoreactivity was more intense and extensive in benign epithelium than in PIN and adenocarcinoma. The number of immunoreactive PIN or cancer cells for PSM and PSA was not predictive of PSA biochemical or clinical failure as defined in this study. CONCLUSIONS: PSM was expressed in all cases of prostate adenocarcinoma, with the greatest extent and intensity observed in the highest grades. The expression increased incrementally from benign epithelium to high grade PIN or adenocarcinoma. Conversely, PSA showed the greatest staining in benign epithelium, with decreased expression incrementally from benign epithelium to high grade PIN or adenocarcinoma. Expression of PSM is clinically useful for the identification of prostate epithelium, particularly PIN or adenocarcinoma, and its expression is regulated independent of PSA. The number of PSM immunoreactive cells was not predictive of recurrence, most likely because of the presence of abundant immunoreactivity in most cases, or because of differential expression in primary and metastatic disease.

Adenocarcinoma↗
PubMed1998

Expression of early growth response genes in human prostate cancer.

Early growth-response (EGR) genes are nuclear transcription factors that are implicated in regulating cell proliferation. Because these genes show divergent expression in various human tumors, we sought to determine their expression in nonmalignant and malignant prostate tissues. Total RNA extracted from prostate tissues was probed with EGR-1, EGR-2, and EGR-alpha cDNA for Northern blots and digoxigenin-labeled cRNA for in situ hybridization. Both Northern blot and in situ hybridization analyses demonstrated increased EGR-1, but not EGR-2 or EGR-alpha expression, in malignant prostate tissue as compared with weak expression in nonmalignant tissue. EGR-1 mRNA was quantified in 96 prostate specimens (86 adenocarcinomas representing different Gleason scores and 10 benign tissues showing no histological manifestation of benign prostatic hypertrophy) using in situ hybridization with an 35S-labeled cRNA probe. EGR-1 mRNA was expressed at significantly higher levels in cancer than in normal prostate (P < 0.001). In cancer with Gleason scores 8-10, the expression of EGR-1 was higher compared with those of lower Gleason scores (P < 0.005). Immunohistochemical staining showed predominately basal cell nuclear EGR-1 protein in prostatic acini. Nuclear staining was weak in nonmalignant tissues, more intense in moderately differentiated carcinoma, and most intense in poorly differentiated carcinoma. These results show that EGR-1 is overexpressed in prostate cancer and suggest a role for EGR-1 in prostate cancer growth.

Adenocarcinoma↗
PubMed1998

Pathologic classification of prostate carcinoma: the impact of margin status.

BACKGROUND: A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS: Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS: After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (< or = 0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS: This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification.

Humans↗