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In tumors, the switch to the angiogenic phenotype is thought to be controlled by a balance of positive and negative angiogenic factors. Tissue factor (TF) produced by tumor cells has been implicated in the regulation of this "angiogenic switch" through its ability to concurrently induce the expression of angiogenic molecules such as vascular endothelial cell growth factor (VEGF), while inhibiting the expression of anti-angiogenic molecules such as thrombospondin 2. We have examined TF expression and its relationship to angiogenesis and tumor progression in human prostate carcinomas. Most of the prostate carcinoma specimens examined (73%; n = 67) express high levels of TF. Immunohistochemical analysis localized TF expression to the epithelial cells of malignant glands. TF expression was significantly correlated with tumor angiogenesis as measured by the microvessel density (MVD). In addition, TF expression was correlated with the preoperative PSA level, a strong predictor of recurrence in prostate carcinomas. Our findings show that TF expression by the malignant glands in prostate cancer is common and suggest a role for this molecule in regulating prostate cancer progression and angiogenesis.

Background: There is limited information on outcomes of prostate carcinoma treatments given to screened patient populations for whom cancer is usually detected at an earlier stage., Methods: The authors conducted a cross-sectional evaluation of quality-of-life outcomes for men with prostate carcinoma detected in screening studies at a university center. Of 2234 men diagnosed with prostate carcinoma between 1989 and 1997, 74% responded to the questionnaire. Primary management included radical prostatectomy (76%), radiotherapy (11%), observation (7%), hormonal therapy (4%), and cryoablation (2%). Main outcome measures included validated measurements of quality of life, urinary and sexual functioning, and bother (36-item RAND Health Survey, UCLA Prostate Cancer Index)., Results: After controlling for demographic factors, differences among treatment groups were found for all general quality-of-life outcomes, with increased impairment in men who underwent hormonal therapy (all P values <0.05). Urinary and sexual function and bother were also significantly related to treatment. However, among men followed for > or =12 months, only 9% reported a moderate or major problem with urinary control. Sexual functioning was a moderate or major problem following treatment for 58% treated with prostatectomy, 48% treated with radiotherapy, 64% treated with hormonal therapy, 45% treated with cryoablation, and 30% managed with observation. Approximately one-third of the men younger than 70 years who underwent radical prostatectomy maintained adequate sexual functioning posttreatment., Conclusions: Up to 6 years after diagnosis, the majority of men with prostate carcinoma detected by screening were bothered by their current sexual function, regardless of treatment. In contrast, most men were not bothered by their current urinary function., (Copyright 2000 American Cancer Society.)

Background: Increasingly, prostate carcinoma is diagnosed through screening. However, little is known regarding factors that influence a patient's decision concerning the treatment choices presented to him., Methods: Subjects were prostate carcinoma patients detected through the Washington University PSA Prostate Cancer Screening Program between September 1989 and June 1998. The sources of data were the prostate specific antigen (PSA) screening database and follow-up questionnaire., Results: Among 1809 study subjects, 79.2% chose radical prostatectomy (RP), 12.4% chose radiation therapy, and 8.4% chose watchful waiting (WW) as their decision regarding primary treatment. In bivariate analyses, education, income, age, indication for prostate biopsy, comorbidity score, serum PSA level, clinical stage, and pretreatment urinary and sexual function were associated significantly with treatment choice, but race, marital status, and Gleason grade were not. In a multivariate analysis, age, race, clinical stage, PSA level, and pretreatment urinary and sexual function were found to be associated significantly with treatment choice. For every 5-year decrease in age, the odds for choosing RP versus WW increased by 276%; for every 1-ng increase in PSA, the odds for choosing RP versus WW increased by 12%. Non-African-American patients were greater than four times more likely to select RP versus WW. Patients with T2 tumors and those with normal pretreatment urinary function were three times more likely and twice more likely to choose RP versus WW, respectively., Conclusions: In the current study, RP was the most widely used treatment in patients with screen-detected prostate carcinoma. Age, race, PSA level, clinical stage, and pretreatment urinary and sexual function were significant factors influencing treatment selection., (Copyright 2000 American Cancer Society.)

Purpose: We update results in a series of consecutive patients treated with anatomic radical retropubic prostatectomy regarding recovery of erections, urinary continence and postoperative complications., Materials and Methods: One surgeon performed anatomic radical retropubic prostatectomy on 1,870 men, using the nerve sparing modification when feasible. We evaluated recovery of erections and urinary continence in men followed for a minimum of 18 months. Patients who were not reliably potent before surgery, did not undergo a nerve sparing procedure, or received hormonal therapy or postoperative adjuvant radiotherapy were excluded from the analysis of potency rates but not of continence rates. Other postoperative complications were evaluated for the entire patient population., Results: Recovery of erections occurred in 68% of preoperatively potent men treated with bilateral (543 of 798) and 47% treated with unilateral (28 of 60) nerve sparing surgery. Recovery of erections was more likely with bilateral than with unilateral nerve sparing surgery in patients less than 70 years old (71 versus 48%, p<0.001) compared with patients with age 70 years old or older (48 versus 40%, p = 0.6). Recovery of urinary continence occurred in 92% (1,223 of 1,325 men) and was associated with younger age (p<0.0001) but not with tumor stage (p = 0.2) or nerve sparing surgery (p = 0.3). Postoperative complications occurred in 10% of patients overall and were associated with older age (p<0.002) but the incidence declined significantly with increasing experience of the surgeon (p<0.0001). There was no operative mortality., Conclusions: Anatomic radical retropubic prostatectomy with the nerve sparing modification can be performed with favorable results in preserving potency and urinary continence. Better results are achieved in young men with organ confined cancer. Other complications can be reduced with increasing surgeon experience.

Purpose: We evaluated correlates of patient reported dissatisfaction with treatment of prostate cancer detected by screening., Materials and Methods: We performed a cross-sectional retrospective study to evaluate the correlates of dissatisfaction with treatment in 1,651 patients in whom prostate cancer was detected through serial screening. We included demographic and clinical characteristics in the independent and control variables, and we validated measurements of quality of life outcomes., Results: Overall 11% of patients were dissatisfied with the treatment received. Differences in the rates of dissatisfaction with treatment were not statistically significant across treatment groups (11% for retropubic radical prostatectomy, 21% for perineal radical prostatectomy, 14% for radiotherapy, 8% for observation, 8% for hormonal treatment and 4% for cryoablation, p = 0.1). Patient age, race, followup interval, marital status, education and co-morbid conditions were not significant correlates of dissatisfaction with treatment (for all characteristics p> or =0.05). Urinary function and bothersomeness were associated with dissatisfaction with treatment (p<0.0001), whereas sexual function and bothersomeness were not (p>0.05). Multivariate analysis revealed that urinary function and bothersomeness were also the only significant correlates of dissatisfaction with treatment., Conclusions: Of patients in whom prostate cancer was detected by screening 11% were dissatisfied with treatment. Urinary function and bothersomeness were the only important correlates of dissatisfaction.

Purpose: We compare clinicopathological features, and cancer recurrence and survival rates in men with stage T1c versus T2a or T2b prostate cancer., Materials and Methods: From 1988 through 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in 1,620 men with a mean age plus or minus standard deviation of 62.3 +/- 7 years. Clinical stage was T1c in 39%, T2a in 22% and T2b in 39% of patients. Patients were followed with semiannual prostate specific antigen (PSA) measurement and annual digital rectal examination. Serum total PSA greater than 0.3 ng./ml., histologically confirmed local tumor recurrence or distant metastases were considered evidence of cancer recurrence. Simple univariate statistics were used to compare clinical and pathological features by clinical stage, and multivariate Cox models were used to compare 5-year recurrence-free probabilities . The 5-year all cause and disease specific survival rates were calculated using Kaplan-Meier product limit estimates., Results: Mean patient age was younger for the clinical stage T1c group (61 years) than for the T2a (62 years) or T2b (64 years) group. Mean preoperative PSA and the percentage of patients with biopsy Gleason score 8 to 10 were more favorable for the T1c (8 ng./ml., 3%) and T2a (7, 5%) groups than for the T2b group (11, 6%). Cancerous surgical margins, seminal vesicle invasion and lymph node metastases were also less frequent in the T1c (20, 5 and 0.8%, respectively) and T2a (23, 5 and 0.3%) groups than in the T2b group (29, 11 and 1.8%). The 5-year recurrence-free survival rate was 85% for T1c, 83% for T2a and 72% for T2b cases. Multivariate analysis indicated a decreased risk of recurrence for the T1c group compared to the T2a and T2b groups. The 5-year disease specific survival rate was 100% for the T1c and T2a groups, and 97% for the T2b group., Conclusions: Clinical and pathological features were similar for stages T1c and T2a, and different from stage T2b cancers. The 5-year recurrence-free survival was similar for T1c and T2a (log rank 0.89, p = 0.34), and higher than that for T2b (log rank 34.5, p <0.0001) cancers. However, controlling for all other prognostic factors on a Cox multivariate model, the risk of cancer recurrence was decreased for T1c compared to T2a and T2b disease. The detection of nonpalpable prostate cancer appears to be advantageous for intermediate-term cancer control.

Purpose: Favorable results with 125iodine (I) brachytherapy have been reported in select patients with localized prostate cancer. We evaluate the results of radical prostatectomy in patients matched for similar pretreatment clinicopathological characteristics., Materials and Methods: From May 1983 to April 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in 1,952 men (mean age plus or minus standard deviation 63+/-7 years), of whom 1,364 had Gleason score 6 or less on preoperative needle biopsy, a preoperative serum prostate specific antigen (PSA) value available and clinical stage T1 or T2 disease. We categorized all patients by preoperative Gleason score, preoperative PSA and clinical stage. For each Gleason score-by-PSA stratum we randomly selected by computer the number of men necessary to achieve the same overall distribution of clinical characteristics as in a series of patients treated with brachytherapy. All men were followed with semiannual PSA measurements and annual digital rectal examinations. Serum PSA greater than 0.3 ng/ml was considered evidence of cancer recurrence. Simple univariate statistics were used to compare clinical characteristics between series, and 7-year recurrence-free survival was estimated using Kaplan-Meier product limit estimates. To avoid a possible chance extreme result from 1 random sample we estimated 7-year recurrence-free survival in 5 computer selected random samples of our population., Results: Mean 7-year recurrence-free survival was 84% (95% confidence intervals 78 to 89) for the radical prostatectomy series compared to 79% (confidence intervals not provided) for the 125I brachytherapy series., Conclusions: Radical prostatectomy yielded a proportionately but not statistically significant higher 7-year probability of nonprogression than 125I brachytherapy in patients with favorable clinicopathological characteristics. Comparisons are confounded by residual differences in clinicopathological features of tumors between groups and different treatment end points to determine outcomes. Further prospective, randomized clinical trials are required for valid comparisons.

Purpose: We evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum prostate specific antigen (PSA) 4 ng./ml. or less. We also evaluated the stage and grade of cancers detected., Materials and Methods: We screened 22,513 community volunteers by PSA testing and digital rectal examination at 6-month intervals. Biopsy was recommended when either test was suspicious for cancer. In the subset of 2,703 white and black men in whom PSA was 4 ng./ml. or less and digital rectal examination was suspicious for prostate cancer we compared compliance with biopsy recommendations, cancer detection rates, and stage and grade of cancers detected. We then correlated these results with patient age, race and serum PSA concentration. We performed multivariate logistic regression analysis to predict cancer based on clinical characteristics, and evaluated the positive predictive value of digital rectal examination for detecting cancer as stratified by race and PSA., Results: Of the men 70% underwent biopsy with no difference in compliance according to age, race or PSA level. The 13% cancer detection rate correlated with age, race and PSA (p <0.003). The positive predictive value of a suspicious digital rectal examination was 5, 14 and 30% in men with PSA 0 to 1.0, 1.1 to 2.5 and 2.6 to 4.0 ng./ml., respectively. All cancers were clinically localized. Of the 72% of cases that were surgically staged 82% were organ confined and 78% were moderately differentiated., Conclusions: The positive predictive value of suspicious digital rectal examination was appreciable in men with low serum PSA. The majority of cancer cases detected by digital rectal examination had features of clinically important and potentially curable disease.

Purpose: We evaluated differences in the prostate cancer detection rate among black and white men with serum prostate specific antigen (PSA) levels between 2.6 and 4.0 ng./ml., and benign findings on digital rectal examination., Materials and Methods: From May 1995 through June 1997 we screened 14,209 white and 1,004 black men 50 years old or older with serum PSA and rectal examinations at 6-month intervals. If PSA was greater than 2.5 ng./ml. or the rectal examination was suspicious for cancer, we recommended an ultrasound guided sextant biopsy of the prostate. We compared differences in clinical characteristics, compliance with the recommendation for biopsy, cancer detection rate, and stage and grade of tumors detected for 924 white and 57 black men., Results: Black men were younger (60 versus 63 years old, p = 0.005) and presented with slightly higher PSA levels (3.3 versus 3.1 ng./ml., p = 0.03) than white men. Overall cancer detection rate was 27% (106 of 391 patients), with cancer detection 2-fold higher among black (13 of 29, 45%) than among white (93 of 362, 26%) men (p = 0.03, odds ratio 2.4, 95% confidence interval 1.1 to 5.1). Controlling for age, total PSA, PSA density, percent free PSA and number of prior screening visits, race remained a significant predictor of cancer (adjusted odds ratio 3.4, confidence interval 1.4 to 8.4). We found trends for worse pathological stage and grade among black men but these differences did not reach statistical significance., Conclusions: Black race was an independent predictor of prostate cancer even at lower PSA cutoffs (2.6 to 4.0 ng./ml.). Although the positive predictive value for cancer detection was relatively high in black men, long-term outcomes studies are necessary to determine whether the use of lower PSA cutoffs would result in favorable shifts in cancer stage and grade, and a reduction in racial differences in prostate cancer mortality rates.