Statistical modeling using preoperative prognostic variables in predicting extracapsular extension and progression after radical prostatectomy for prostate cancer

OBJECTIVE: To predict the risk of extracapsular extension and postoperative recurrence before radical prostatectomy (RP) for prostate cancer. METHODS: We performed multivariate Cox regression analysis on preoperative variables in 260 clinically localized prostate cancer patients who underwent RP. With these data, we constructed a relative risk of recurrence (Rr) equation and an equation to predict the probability of extracapsular extension (PECE) before RP. RESULTS: Rr is calculated as exp[(0.47 x race + 0.14 x PSAST) + (0.13 x worst biopsy Gleason sum) + (1.03 x stage T1c) + (1.55 x stage T2b,c)], where PSAST indicates a sigmoidal transformation of prostate-specific antigen. PECE is calculated as 1/[1 + exp(-Z)], where Z = -2.47 + 0.15 (PSAST) + 0.31 (worst biopsy Gleason sum) + 0.18 (race) + 0.16 (stage T1c) + 0.38 (stage T2b,c). CONCLUSION: These two equations can be used preoperatively to predict the probability of extracapsular disease and the risk of prostate-specific antigen recurrence in patients undergoing RP.     

The effects of FR167653 in extended liver resection with ischemia in dogs

PURPOSE: We assess the neovascularity of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody CD34 in an attempt to identify associations between angiogenesis and disease progression following radical prostatectomy. MATERIALS AND METHODS: Microvascularity was evaluated using the CD34 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 149 patients followed from 3 to 10 years (mean 6.6). Vessels were quantified by counting a minimum of 2 selected microscopic fields (200x, 0.754 mm.2) from each tumor, area of prostatic intraepithelial neoplasia and prostatic hyperplasia, and given a numerical value representing the microvessel density count. RESULTS: Mean microvessel density count did not vary significantly with age or race. There was a significant association between the count and nuclear grade, Gleason sum and pathological stage. Cox survival analysis shows that microvessel density is significantly related to time to recurrence when considered as a continuous variable (p=0.03) as well as dichotomous variable (p=0.007) (microvessel density count less than 90 and 90 or greater). The 5-year recurrence-free survival was significantly higher for patients with a count less than 90 (71%) than for those with a count 90 or greater (51%) (p=0.006). The 5-year recurrence-free survival was also significantly different when microvessel density was used as a continuous variable (p=0.02). Controlling for stage, Gleason sum, race and nuclear grade, microvessel density remained significant in predicting recurrence (p=0.03) but when pretreatment prostate specific antigen was included in the model the count was no longer significant. The microvessel density count in the tumor area significantly increased with increasing Gleason sum and nuclear grade but it did not increase significantly in the adjacent benign prostate or areas of prostatic intraepithelial neoplasia in the same specimen. CONCLUSIONS: Microvascularity or neovascularity as measured by the CD34 antigen may be a prognostic marker of recurrence for prostate cancer patients after radical prostatectomy but more study in prostate specific antigen era patients with sufficient followup is needed.     

Epidermodysplasia verruciformis with neurological manifestations

BACKGROUND: Few published studies have combined clinical prognostic factors into risk profiles that can be used to predict the likelihood of recurrence or metastatic progression in patients following treatment of prostate cancer. We developed a nomogram that allows prediction of disease recurrence through use of preoperative clinical factors for patients with clinically localized prostate cancer who are candidates for treatment with a radical prostatectomy. METHODS: By use of Cox proportional hazards regression analysis, we modeled the clinical data and disease follow-up for 983 men with clinically localized prostate cancer whom we intended to treat with a radical prostatectomy. Clinical data included pretreatment serum prostate-specific antigen levels, biopsy Gleason scores, and clinical stage. Treatment failure was recorded when there was clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on a separate sample of 168 men, also from our institution. RESULTS: Treatment failure (i.e., cancer recurrence) was noted in 196 of the 983 men, and the patients without failure had a median follow-up of 30 months (range, 1-146 months). The 5-year probability of freedom from failure for the cohort was 73% (95% confidence interval = 69%-76%). The predictions from the nomogram appeared accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.79. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among men with clinically localized prostate cancer treated with radical prostatectomy.     

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.     

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.     

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.     

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.     

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.     

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.     

The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells

OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation and prostate-specific antigen (PSA) level, alone and in combination, to predict regional nodal metastases in individual patients with localized prostate cancer. PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy Gleason sum and PSA, alone and in combination, to predict nodal metastases in an individual patient was examined. The study included 689 patients who had laparoscopic or open pelvic lymph node dissection for clinical stage T1-3 prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test and logistic regression were used for continuous, ordinal, categorical, and multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage, DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were significant predictors of lymph node status in a multivariate analysis. However, based on a receiver operating characteristic curve, a model with satisfactory sensitivity and specificity could not be obtained. CONCLUSION: Current estimations of primary prostate cancer biology using pre-operative PSA level, clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict nodal metastases, and pelvic lymphadenectomy remains the definitive method of detection.     

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.     

Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy. The Lagos V Study Group

OBJECTIVES: This study sought to characterize the postoperative prostate-specific antigen (PSA) doubling time and time to biochemical recurrence in patients who have failed radical prostatectomy. METHODS: Of 539 consecutive patients who underwent radical prostatectomy between 1984 and 1992, postoperative PSA levels in 80 initially became undetectable (less than 0.07 ng/mL) before eventually increasing, as evidenced by rising PSA levels above the residual cancer detection limit of the Tosoh AIA-600 immunoassay run in the ultrasensitive mode (i.e., 0.07 ng/mL or higher). The PSA doubling time and time to biochemical recurrence were calculated for each of the 80 patients and were correlated with the histopathologic variables from the operative specimen. RESULTS: Postoperative PSA doubling times were predicted by the extent of capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and tumor volume on univariate analysis and by capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and patient age on multivariate analysis. Times to recurrence were predicted by the presence of positive margins and percent Gleason grade 4 or 5 in both univariate and multivariate regression models. The PSA doubling time did not correlate with recurrence time. The median PSA doubling time for all patients was 284 days, and the median time to recurrence was 648 days. CONCLUSIONS: These results demonstrate that PSA doubling time and recurrence time are indicative of different biologic characteristics of recurrent prostate cancer: Doubling time appears to represent the aggressiveness of the original prostate cancer, whereas time to recurrence reflects the extent of residual postoperative disease. This information should aid in the selection of men who need greater vigilance during postoperative surveillance.     

Pathologic features and clinical outcome after anatomic radical prostatectomy by transcoccygeal approach

OBJECTIVES: A nonrandomized prospective study was conducted aimed at verifying the clinical outcome and pathologic features of a group of patients submitted to transcoccygeal radical prostatectomy. METHODS: Radical transcoccygeal prostatectomy was performed at our institution in 26 patients after laparoscopic (24 cases) or open surgical (2 cases) pelvic lymphadenectomy. Eighteen patients were selected because they were considered to be at risk for nodal metastases on the basis of preoperative staging (prostate-specific antigen level of 20 ng/mL or greater and/or Gleason score greater than 5); the remaining 8 manifested incidental prostate carcinoma. RESULTS: Intraoperative complications included rectal injury in 1 patient (3.8%) and massive blood loss in another. Transitory leakage at the site of the urethrovesical anastomosis and urethrorectal fistula occurred postoperatively in 2 patients. The rate of positive surgical margins was 26.9%. The mean follow-up time is 27 months (range 3 to 39 months). Total urinary continence was obtained in 21 patients (80.8%); 5 patients (19.2%) still require urinary pads. Four patients (15.4%) have experienced tumor recurrence evidenced only by increased serum prostate-specific antigen levels. Local tumor recurrence with positive biopsy of the urethrovesical junction was diagnosed in 3 patients (11.5%), and 1 (3.8%) experienced systemic tumor recurrence. CONCLUSIONS: Radical transcoccygeal prostatectomy is a safe procedure for the surgical treatment of prostate cancer, both from a clinical and a pathologic point of view. Operative complication as well as pathologic features and clinical outcome reported in this series of patients must be related to selection criteria used in most cases. The exact role of radical transcoccygeal prostatectomy in the clinical setting has yet to be defined. According to these preliminary results, radical transcoccygeal prostatectomy should be further investigated in the treatment of incidental carcinoma after transurethral resection of the prostate or suprapubic prostatectomy and could become an elective indication in such cases.     

Adjuvant treatment after radical prostatectomy in prostatic carcinoma (pT3 or pTxN+): prognostic factors and results

Adjuvant therapy after radical prostatectomy should ideally be limited to those patients at greatest risk for cancer recurrence, but identification of these patients remains a challenge. The local control rate in a group of 7494 patients undergoing radical prostatectomy for patients with pT2a disease of 76% is not different to pN+ disease of 80%. 95% of the pT3 patients were pN+ .90% of them received adjuvant treatment but only few patients with organ-confined cancer. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients with pathologically organ-confined prostate cancer according to risk of progression. Although tumor volume has traditionally been regarded as the most important prognostic factor in patients with localized prostate cancer, a recent multivariate analysis has shown that tumor volume is not an independent predictor. Moreover, accurate measurement of tumor volume is extremely difficult. Preoperative serum PSA levels, clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. Patients with the lowest score had a 92% progression free survival rate at 5 years, compared to only 39% of those with the highest scores. Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.     

A double blind, prospective trial of topical ciprofloxacin versus normal saline solution in the treatment of otorrhoea

CONTEXT: The generalizability of currently available estimates of survival after radical prostatectomy is theoretically limited. OBJECTIVE: To obtain generalizable estimates of survival after radical prostatectomy. DESIGN: A population-based retrospective cohort study. SETTING: Nine regions of the United States. PATIENTS: Patients who were diagnosed with prostate cancer between 1983 and 1987 and underwent radical prostatectomy and lymph node dissection. MAIN OUTCOME MEASURES: Proportional hazards models incorporating geographical region, age, race, pathological stage, lymph node involvement, and tumor grade to identify independent correlates of disease-specific and overall survival and life table analyses to estimate 10-year survival distributions. RESULTS: A total of 3626 patients with a mean age of 65 years were included in the study; 92.6% were white, 54.2% had moderate-grade cancer, 60.4% had no extension beyond the prostate, and 91.2% had no lymph node involvement. Using San Francisco-Oakland, Calif, as a reference region, no other region was significantly associated with a risk of disease-specific or overall mortality. Older age and black race were independently associated with worse overall but not disease-specific survival. Higher grade, extension beyond the prostate, and lymph node involvement were independently associated with worse disease-specific and overall survival. Estimates of 10-year disease-specific survival ranged from 75% to 97% for patients with well-differentiated and moderately differentiated cancers and from 60% to 86% for patients with poorly differentiated cancers. CONCLUSIONS: Neither disease-specific nor overall survival varied by region, suggesting geographically uniform assessments of risk in patient selection for radical prostatectomy. Across regions, overall survival varied by patient and prostate cancer characteristics while disease-specific survival varied substantially by prostate cancer but not patient characteristics. The present analyses provide the most generalizable current estimates of survival after radical prostatectomy.     

Loss of expression of transforming growth factor-beta receptors is associated with poor prognosis in prostate cancer patients

Transforming growth factor beta (TGF-beta) is a potent inhibitor of proliferation in most cells and exerts its effects through an interaction with membrane receptors type I (TGF-betaRI) and type II (TGF-betaRII). Recently, we have demonstrated a correlation between the loss of expression of TGF-betaRI and TGF-betaRII and increasing Gleason score in archival human prostate cancer tissues. To evaluate the potential prognostic value of this observation, the present study investigated the expression of TGF-beta receptors in association with disease progression after the initial diagnosis in 52 archival human prostate cancer tissues. The expression of both TGF-betaRI and TGF-betaRII was correlated with the Gleason score, clinical tumor stage, 4-year survival rate, and serological recurrence rate after radical prostatectomy. Results revealed that there was a significant association between the Gleason score and the loss of expression of TGF-betaRI (P < 0.025) and TGF-betaRII (P < 0.01). However, only the loss of TGF-betaRI expression showed a statistically significant association with the clinical tumor stage (P < 0.05), 4-year survival rate (P < 0.05), and serological recurrence rate after radical prostatectomy (P < 0.025). Therefore, these data indicate that the loss of TGF-betaRI expression as measured by immunohistochemical staining may be a potential prognostic marker in prostate cancer patients.     

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.     

Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA) progression analysis

OBJECTIVES: To evaluate the relative efficacy of brachytherapy to radical prostatectomy, we compared biochemical progression rates from a published series of men who underwent iodine 125 (125I) interstitial radiotherapy for localized prostate cancer to a similar group of men who underwent anatomic radical prostatectomy using appropriate end points. METHODS: Seventy-six men who underwent anatomic radical prostatectomy between 1988 and 1990 were carefully matched for Gleason score and clinical stage to a recently reported contemporary series of patients treated at another institution with 125I brachytherapy without adjuvant treatment. The definition of biochemical progression was a serum PSA level greater than 0.2 ng/mL after anatomic radical prostatectomy and greater than 0.5 ng/mL for brachytherapy-treated patients. RESULTS: The 7-year actuarial PSA progression-free survival following anatomic radical prostatectomy was 97.8% (95% confidence interval [CI], 85.6% to 99.7%) for this group of men selected to match the brachytherapy group, compared to 79% (95% CI not published) for men treated with 125I interstitial radiotherapy. CONCLUSIONS: Using comparative end points for biochemical-free progression, failure rates may be higher following 125I interstitial radiotherapy compared to anatomic radical prostatectomy. These data provide a better comparison of biochemical progression than previously published studies and emphasize the need for caution in interpreting the relative efficacy of brachytherapy in controlling localized prostate cancer.     

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.