Biomedical subjects

Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

139 records · Page 8Linked to original sources

PubMed2002

Comparison of WHO/ISUP and WHO classification of noninvasive papillary urothelial neoplasms for risk of progression.

OBJECTIVES: To investigate the relation of the World Health Organization/International Society of Urological Pathology (WHO/ISUP) system for bladder neoplasia to prognosis. METHODS: A total of 134 patients with pTa bladder tumors were identified. We excluded cases with prior or concurrent carcinoma in situ or invasion (pT1 or pT2). Progression was defined as a tumor recurrence with either lamina propria (pT1) or muscularis propria (pT2) invasion or carcinoma in situ. Age at diagnosis, sex, tumor size, multifocality, and grade (WHO, WHO/ISUP) were entered into a Cox multivariate analysis to predict progression. RESULTS: The distribution of WHO papilloma, WHO G1, WHO G2, and WHO G3 was 5.2%, 31.3%, 59%, and 4.5%, respectively. The distribution of WHO/ISUP papilloma, tumors of low malignant potential, low-grade carcinomas, and high-grade carcinomas was 2.2%, 21.6%, 13%, and 21.6%, respectively. The mean and median follow-up was 56.2 and 50 months, respectively. The 90-month actuarial risk of progression for WHO papilloma, G1, G2, and G3 was 0%, 11%, 24%, and 60%, respectively. The corresponding progression rate for WHO/ISUP papilloma, tumors of low malignant potential, low-grade carcinoma, and high-grade carcinoma was 0%, 8%, 13%, and 51%, respectively. In separate analyses, WHO grade (P = 0.003) and tumor size (P = 0.03), as well as WHO/ISUP (P = 0.002) and tumor size (P = 0.04), independently predicted progression. CONCLUSIONS: WHO G3 has a more rapid progression rate and a slightly worse long-term progression rate compared with WHO/ISUP high-grade carcinoma. However, although only 4.5% of tumors were WHO G3, we were able to classify 21.6% as WHO/ISUP high-grade carcinoma with a poor prognosis. Use of the WHO/ISUP system allows urologists to more closely follow a larger group of patients at high risk of progression.

Carcinoma in Situ↗

PubMed2002

Prediction of outcome after radical prostatectomy in men with organ-confined Gleason score 8 to 10 adenocarcinoma.

OBJECTIVES: Most adenocarcinomas of the prostate with a Gleason score greater than 8 at radical prostatectomy have extraprostatic extension and a high risk of progression. With prostate-specific antigen screening, we have seen some cases of earlier detected, organ-confined, high-grade adenocarcinoma. Few data are available as to the likelihood of cure in these cases. METHODS: We reviewed 27 cases of pathologically organ-confined adenocarcinoma with a prostatectomy Gleason score of 8 to 10. To exclude cases with a significant proportion of Gleason pattern 3, we excluded cases of Gleason score 3+5=8 and Gleason score 5+3=8. All cases of Gleason score 8 at radical prostatectomy were Gleason score 4+4. The prognostic value of the clinical parameters (clinical stage, serum prostate-specific antigen level, age) and pathologic factors (biopsy Gleason score, radical prostatectomy Gleason score, prostatectomy tumor volume) were tested to predict postoperative progression. RESULTS: The mean age at diagnosis was 59.7 years (range 46 to 69) with preoperative serum prostate-specific antigen levels ranging from 1.4 to 28 ng/mL (mean 7.8). All tumors were classified as pathologic Stage T2N0Mx. Fifteen patients (55.6%) had a Gleason score of 8, 11 patients (40.7%) had a Gleason score of 9, and 1 had a Gleason score of 10 (3.7%). Tumor volumes ranged from 0.02 to 1.44 cm(3) (mean 0.56). Follow-up information was available for all men. The mean follow-up for those without progression was 30.6 months (range 7 to 73) and for those with progression was 23.6 months (range 9 to 44). The 33-month actuarial risk of progression was 32%, with 10 men developing progression during the study. None of the preoperative or postoperative variables predicted progression. CONCLUSIONS: Even when high-grade tumor is organ confined, it is associated with a relatively unfavorable short-term outcome that is not predictable on the basis of either preoperative clinicopathologic data or postoperative pathologic information obtained from the radical prostatectomy specimen.

Adenocarcinoma↗

PubMed2002

Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.

OBJECTIVES: To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown. METHODS: A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells. RESULTS: At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%. CONCLUSIONS: Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.

Aged↗

PubMed2002

Substratification of stage T1C prostate cancer based on the probability of biochemical recurrence.

OBJECTIVES: To evaluate the influence of preoperative prostate-specific antigen (PSA), biopsy Gleason sum, and prostate biopsy quantitative histologic findings on the probability of biochemical failure in an attempt to identify criteria to substratify Stage T1c prostate cancer more accurately. METHODS: We reviewed the records of 1149 patients who underwent prostatectomy for T1c disease between 1988 and 2000. Biochemical recurrence (PSA 0.2 ng/mL or greater) defined the endpoint in this study. Recursive partitioning analysis was used to establish cutpoints for preoperative PSA level, biopsy Gleason sum, number of positive biopsy cores, and maximal percentage of any single biopsy core involved with cancer. These cutoff values were then evaluated using Kaplan-Meier estimations to determine the probability of remaining biochemically recurrence free. RESULTS: Using a PSA cutpoint of 10 ng/mL or a biopsy Gleason sum of 7, two groups of patients were identified (T1cI and T1cII). The rate of freedom from PSA recurrence at 3, 5, and 10 years after surgery for T1cI was 98%, 96%, and 96%, respectively, and for T1cII was 86%, 83%, and 73%, respectively (P <0.001). For T1cII patients, the greatest percentage of cancer in a single biopsy core was found to be a predictor of biochemical failure on multivariate analysis and, using a cutoff value of 50%, further stratified the PSA recurrence-free rates for the men in group T1cII (90% and 85% versus 75% and 56% at 5 and 10 years after surgery, respectively, P = 0.03). CONCLUSIONS: The results of this study demonstrate that within Stage T1c there are two populations of patients with significantly different recurrence probabilities: T1cI (Gleason sum less than 7 and PSA 10 ng/mL or less) and T1cII (Gleason sum 7 or greater or PSA greater than 10 ng/mL). Furthermore, using a cutpoint of 50% of cancer in a single core of biopsy tissue, additional risk stratification is afforded to men with higher risk "T1cII" cancer.

Aged↗

PubMed2002

Prognostic significance of atypical papillary urothelial hyperplasia.

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms.

Aged↗

PubMed2002

Central zone histology of the prostate: a mimicker of high-grade prostatic intraepithelial neoplasia.

The central zone (CZ) is located at the base of the prostate adjacent to the seminal vesicles. Its histology as a potential mimicker of high-grade prostatic intraepithelial neoplasia (PIN) has not been formally studied. Three groups were evaluated. Group 1 comprised 30 consecutive radical prostatectomy specimens assessed for the extent of CZ and of Roman arch and/or cribriform formation in the CZ. Group 2 comprised 100 consecutive cases of nonconsult prostate needle biopsies, screened in a random blinded fashion to identify CZ histology and the specificity of its identification on biopsy. Group 3 comprised 34 consult cases (1984 to the present) with CZ histology on needle biopsy. For group 1, the average maximum diameter of CZ histology was 5 mm. Two cases (6.7%) did not contain the classic features of CZ histology. The average amount of cribriform and/or Roman arch formation in the areas with CZ histology was 16.5%. In group 2, 10% of prostate needle biopsy cases had CZ histology. Of these, 80% were located on biopsy specimens designated as the base of the prostate, 10% were located in the base and midportion of the prostate, and 10% were located in the midportion of the prostate. For group 3, CZ histology occupied on average 32% of the involved core. The 2 most common histologic features were eosinophilic cytoplasm (97%) and location at the end of a core (97%). Other features were Roman arch formation (59%), a prominent basal cell layer (32%), cribriform formation (26%), and associated thick muscle bundles typical of bladder neck (24%). On average, cribriform and/or Roman arch formation occupied 22% of the CZ area seen on biopsy. Twenty-six of the consult cases were sent in with preliminary outside diagnoses. Of these, 21 (81%) were either PIN or atypical: 11 (42%) high-grade PIN, 7 (27%) PIN, and 3 (12%) atypical glands. Our findings show that CZ histology is distinctive, as seen in radical prostatectomy specimens. Less frequently it is found on needle biopsy, where the presence of Roman arch and/or cribriform formation mimics PIN. Recognition of the distinctive features of CZ histology (i.e., tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer, and lack of cytologic atypia) can help avoid a misdiagnosis of PIN or "atypia" on needle biopsy.

Biopsy, Needle↗

PubMed2002

Should the diagnosis of benign prostatic hyperplasia be made on prostate needle biopsy?

Pathologists frequently sign out benign prostate needle biopsies as "benign prostatic hyperplasia (BPH)". There are no data indicating that a diagnosis of BPH on biopsy correlates with either gland weight or with the International Prostate Symptom Score (IPSS) used to measure urinary obstructive symptoms. We examined biopsies for average percentage of glands and average percentage of glands with papillary infolding per case, maximum percentage of glands and maximum percentage of glands with papillary infolding per core per case, and presence of any stromal nodules per case. BPH was measured in 2 ways: (1) IPSS grouped into 3 categories (mild, moderate, severe) and (2) prostate weight at radical prostatectomy in men with limited cancer. IPSS was classified as follows: mild (n = 12), moderate (n = 13), and severe (n = 10). There was no correlation with IPSS and any of the histologic features measured. For the 41 radical prostatectomy specimens, the average weight was 65.3 g (median, 56.0 g, range, 22 to 117 g). There was no correlation between gland weight and the average or maximum percentage of glands, or average or maximum percentage of glands with papillary infolding. Stromal nodules on biopsy correlated with gland weight. In the 30 cases without stromal nodules on biopsy, the mean gland weight was 51.4 g. In the 11 cases with stromal nodules on biopsy, the mean gland weight was 77.4 g (P = 0.0125). However, stromal nodules were not specific for a large prostate (i.e., a 15 g prostate had stromal nodules on biopsy). With the exception of stromal nodules found on biopsy, histologic findings on biopsy are not specific for either clinical or pathologic BPH. Thus benign prostate biopsies should be signed out merely as "benign prostate tissue."

Adult↗

PubMed2002

Villous adenoma of the urinary tract: a lesion frequently associated with malignancy.

Villous adenomas arising in the urinary tract are rare. We identified 18 cases of villous adenomas of the bladder, urachus, and prostatic urethra. Patients ranged in age from 53 to 93 years with an average age of 69.6 years and a male preponderance of 67%. In six cases (33%), the lesion was pure villous adenoma. In three cases (17%), there was villous adenoma with in situ adenocarcinoma. In six cases (33%) there was villous adenoma with in situ and infiltrating adenocarcinoma. One case (6%) had villous adenomas with in situ (noninvasive) papillary urothelial carcinoma. One case (6%) had villous adenomas with in situ adenocarcinoma and in situ papillary (noninvasive) and infiltrating urothelial carcinoma. The remaining case (6%) had villous adenoma with in situ and infiltrating adenocarcinoma and in situ (noninvasive) papillary and infiltrating urothelial carcinoma. Clinical outcome was available in eight of the cases, with a mean follow-up of 4.6 years. No evidence of recurrence was found in two patients with pure villous adenoma or in two patients with villous adenoma and only in situ adenocarcinoma, all of whom were treated by nonradical excision. However, two of three cases with infiltrating cancer developed distant metastases despite radical surgery; the remaining patient was disease-free 11 years after transurethral resection. The case with villous adenoma and in situ urothelial carcinoma progressed to sarcomatoid urothelial carcinoma following partial cystectomy. Eight of 10 villous adenomas cases studied expressed the epitope for mAbDas1, found on colonic epithelium and primary adenocarcinomas of the bladder and urachus but not on normal or neoplastic urothelium. This study expands the spectrum of histologic features accompanying villous adenomas of the urinary tract. Coexisting infiltrating adenocarcinoma is often present, necessitating thorough sampling of any lesion diagnosed by biopsy as villous adenoma. Pure villous adenoma and those well-sampled lesions also containing in situ adenocarcinoma portend a favorable prognosis, even without radical treatment. Coexisting in situ or infiltrating carcinoma suggests a more aggressive course. Histologically, immunohistochemically, and prognostically, these lesions appear analogous to their counterparts in the intestine.

Adenocarcinoma↗

PubMed2002

Unusual morphologic patterns of basal cell hyperplasia of the prostate.

The distinction of basal cell hyperplasia (BCH) from carcinoma or high-grade prostatic intraepithelial neoplasia may be difficult. We reviewed 25 cases of BCH with unusual features and identified four distinct groups: BCH with intracytoplasmic globules (five cases); BCH with calcifications (eight cases), including one with globules; BCH with squamous features (three cases); and cribriform BCH (nine cases), including two cases with globules. A total of five cases contained prominent nucleoli and/or cytologic atypia. Hyaline cytoplasmic globules have not been described in any other prostatic entity and appear diagnostic of BCH. Calcifications observed in BCH were psammomatous, differing from the fine stippled calcifications occasionally seen in areas of comedonecrosis within high-grade prostatic carcinoma. Basal cell hyperplasia with squamous features differed from squamous differentiation in carcinomas (adenosquamous carcinoma) and from benign foci of squamous differentiation seen associated with either prostatic infarcts or with hormonal therapy. Whereas cribriform prostatic intraepithelial neoplasia and cribriform cancer glands represent a single glandular unit with punched out lumina, many of the glands within a focus of cribriform BCH appeared as fused individual BCH glands. The use of cytokeratin 34betaE12 can help in difficult cases. In cribriform BCH high-molecular-weight cytokeratin shows multilayered staining of the basal cells in some of the glands and a continuous layer of immunoreactivity. Cribriform prostatic intraepithelial neoplasia demonstrates an interrupted immunoreactive single cell layer of basal cells. Recognition of the architectural and cytologic features of unusual morphologies of BCH can be used to facilitate its diagnosis and differentiation from prostatic carcinoma and high-grade prostatic intraepithelial neoplasia.

Carcinoma, Adenosquamous↗

PubMed2002

Can basal cells be seen in adenocarcinoma of the prostate?: an immunohistochemical study using high molecular weight cytokeratin (clone 34betaE12) antibody.

Rare reports describe high molecular weight cytokeratin (clone 34betaE12) antibody cross-reactivity in scattered prostate carcinoma (PCa) cells, yet most often not in a true basal cell distribution. There are no data specifically describing 34betaE12 reactivity in basal cells in PCa. From August 10, 1995 to May 1, 2000, a total of 3198 consult prostate needle biopsies with PCa and a 34betaE12 immunoperoxidase stain were reviewed at our institution. Thirty-six cases (1.1%), which on hematoxylin and eosin stain were unequivocal cancer, had at least focal 34betaE12 positivity in a basal cell distribution. Twenty-five had original diagnostic slides for review. All cancers were Gleason score 6. The mean number of cancer glands per case was 36.9 (10-108) with an average of 39% of glands (1-100%) showing 34betaE12 reactivity. Twenty-one cases had patchy staining in a basal cell distribution with one other case showing continuous staining. An additional case showed mainly tumor cell reactivity with rare basal cell staining. The final two cases showed a zonal staining pattern with small glands toward one side of the lesion showing basal cells [one with high grade prostatic intraepithelial neoplasia (HGPIN); one without HGPIN]. HGPIN was present in 16 of 25 (64%) cases adjacent to PCa. The mean number of HGPIN glands was 1.36 (1-6). In cases with HGPIN the mean ratio of cancer to HGPIN glands was 6.8 (0.5-13.0). In 12 cases in which the lesion was still present on deeper sectioning, we were able to confirm in nine cases the presence of basal cells using antibodies to p63, another marker for prostatic basal cells. Four of the 25 men underwent radical prostatectomy; all showed Gleason score 6 PCa. Three radical prostatectomies demonstrated 34betaE12 reactivity: two with patchy staining in a basal cell distribution and one with mainly tumor cell staining. Adjacent HGPIN was present in all three radical prostatectomy specimens. Rare lesions with the appearance of PCa show 34betaE12 staining in a basal cell distribution either from retention of basal cells by early invasive cancer or from HGPIN outpouching. The lack of adjacent HGPIN in some cases and the large ratio of small atypical glands to HGPIN glands argue against HGPIN outpouching as the sole explanation. In cases with adjacent HGPIN a comparison of the proximity and number of the small, atypical, infiltrative appearing glands to HGPIN is helpful. The diagnosis of PCa in the face of positive 34betaE12 basal cell staining should be made with extreme caution, only in the face of unequivocal cancer on the hematoxylin and eosin stain.

Adenocarcinoma↗

PubMed2002

Expectant management of nonpalpable prostate cancer with curative intent: preliminary results.

PURPOSE: We evaluate a strategy of expectant management for men with stage T1c prostate cancer. MATERIALS AND METHODS: A total of 81 men (median age 65 years, range 52 to 72) with stage T1c prostate cancer who were thought to have small volume prostate cancer based on needle biopsy findings and prostate specific antigen (PSA) density were followed for more than 1 year with semiannual PSA and digital rectal examination, and annual prostate biopsies (median followup 23 months, range 12 to 58). A recommendation for treatment was made if disease progression was indicated by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer, greater than 50% involvement of any core with cancer). Curable disease was defined on pathological examination of radical prostatectomy specimens as 1) organ confined cancer of Gleason score 7 or less, 2) cancer with extraprostatic extension of Gleason score 7 (3+4) or less with negative margins, seminal vesicles and lymph nodes, or 3) cancer of Gleason score 6 or less regardless of margin status or extraprostatic extension if negative seminal vesicles and lymph nodes. RESULTS: Of the 81 men 25 (31%) had progression of disease at followup. PSA density was statistically significantly higher (p = 0.01) and the percentage of free PSA was statistically significantly lower (p = 0.04) in men with compared to those without disease progression. Disease progression occurred in 22 of 39 men (56%) with every followup biopsy showing cancer compared to 3 of 42 (2%) men with 1 or more negative followup biopsies (p <0.001). Of the 25 men with progression 13 underwent radical prostatectomy and 12 of 13 (92%) had curable cancers. CONCLUSIONS: Expectant management with curative intent may be a reasonable alternative for carefully selected older men who are thought to have small volume cancers.

Aged↗

PubMed2002

Gleason score 7 prostate cancer on needle biopsy: is the prognostic difference in Gleason scores 4 + 3 and 3 + 4 independent of the number of involved cores?

PURPOSE: We addressed whether Gleason score 3 + 4 = 7 and 4 + 3 = 7 cancers on needle biopsy behave differently and whether this behavior is independent of the number of cores involved by cancer. If it is not an independent predictor of prognosis, one may report Gleason score 7 cancer with the number of positive cores without regard to whether the primary pattern was 3 or 4. This practice would remove a source of poor interobserver reproducibility when grading prostate cancer on needle biopsy. MATERIALS AND METHODS: We identified 537 patients with Gleason score 7 tumors on biopsy. The results of patient preoperative digital rectal examination, serum prostate specific antigen (PSA) measurement and age were used to predict 4 outcomes based on assessment of the corresponding radical prostatectomy specimens, including 1) pathological stage (organ confined, focal extraprostatic extension, nonfocal extraprostatic extension or seminal vesicle-lymph node involvement), 2) organ confinement (yes/no), 3) Gleason score and 4) surgical margin status (positive/negative) RESULTS: Multivariate regression of postoperative Gleason score groups against all 5 input variables (3 + 4 versus 4 + 3, number of positive cores, PSA, age and digital rectal examination) yielded a statistically significant positive correlation with preoperative PSA (p <0.001) and preoperative Gleason scores of 4 + 3 versus 3 + 4 on biopsy (p <0.001). Pathological stage correlated with preoperative PSA (p <0.001), Gleason score 4 + 3 disease (p = 0.016), positive digital rectal examination (p <0.001) and 3 or more positive cores (p = 0.016). Positive surgical margins were predicted only by preoperative PSA (p = 0.001). CONCLUSIONS: Because the biological behavior of biopsy Gleason score 3 + 4 or 4 + 3 of Gleason score 7 cancer differs regardless of the number of cores involved, future nomograms predicting pathological stage would benefit from examining 3 + 4 and 4 + 3 disease separately.

Adult↗

PubMed2002

Prediction of pathological stage in patients with clinical stage T1c prostate cancer: the new challenge.

PURPOSE: We developed an algorithm for predicting the likelihood of organ confined disease in patients with clinical stage T1c prostate cancer using biopsy pathology, computer assisted image analysis and serum prostate specific antigen (PSA). MATERIALS AND METHODS: Of the 557 consecutive men enrolled in this study between October 1998 and January 2000 scheduled for radical prostatectomy at a single institution 386 (69%) presented with clinical stage T1c disease. Study exclusion criteria included neoadjuvant hormonal treatment with luteinizing hormone-releasing hormone, antiandrogen or 5alpha-reductase inhibitors. Preoperative serum, biopsy histology slides, clinical demographic information, prostatectomy pathology and prostate weight data were obtained. Biomarkers assessed included total PSA, complexed PSA, free PSA, the free-to-total PSA ratio, quantitative nuclear grade determined by image analysis, complexed PSA density, and biopsy Gleason grade and score. To determine patient specific quantitative nuclear grade values, images from approximately 125 cancer nuclei were captured per patient from the area of the biopsy section with the highest Gleason score. The variance in 60 nuclear size, shape and chromatin texture descriptors was calculated for each gallery of nuclei. Logistic regression was done to determine the most accurate combination of variables for predicting organ confined prostate cancer. RESULTS: Complete results and data were available on 255 of the 386 men (66%) with an average age plus or minus standard deviation of 58.8 +/- 6 years who had stage T1c disease, including 49 (19%) with pathologically nonorgan confined disease. Logistic regression analysis revealed that quantitative nuclear grade, biopsy Gleason score, total PSA, the calculated free-to-total PSA ratio, complexed PSA and complexed PSA density were univariately significant for predicting organ confined disease (p <0.05). On backward stepwise logistic regression only quantitative nuclear grade, complexed PSA density and Gleason score remained in a model yielding an area under the receiver operating characteristics curve of 82.4%. CONCLUSIONS: The quantitative nuclear grade biomarker was the strongest independent predictor of pathological stage in men with clinical stage T1c prostate cancer when combined with biopsy Gleason score and complexed PSA density data.

Aged↗