An analysis of men with clinically localized prostate cancer who deferred definitive therapy.

PURPOSE: We evaluated expectant management of prostate cancer with definitive treatment deferred until evidence of cancer progression in men with low risk, localized cancers. MATERIALS AND METHODS: We retrospectively reviewed prospectively entered data base records. Patients with low risk cancer who were eligible for definitive therapy but chose deferred management between 1984 and 2001 composed the cohort. Followup included regular evaluations to detect progression by prostate specific antigen (PSA), digital rectal examination, transrectal ultrasound and prostate biopsy. Objective progression was defined by a point scale of changes in prognostic factors. Definitive treatment was recommended in patients with objective progression. RESULTS: The cohort comprised 88 patients with clinical stages T1-2, NX0, M0 prostate cancer, a mean age of 65.3 years and a mean initial PSA of 5.9 ng/ml. Systematic biopsy, which was repeated after the initial diagnostic biopsy, showed no cancer in 61% of cases. During a median followup of 44 months 22 patients had progression. Factors that predicted progression were repeat biopsy showing cancer (p = 0.004) and initial PSA (p = 0.014). Actuarial 5 and 10-year progression-free probabilities were 67% and 55%, respectively. Of the 31 patients treated 17 underwent radical prostatectomy, 13 received radiation therapy and 1 received androgen ablation. Seven men who did not show objective progression were treated because of anxiety. Only 1 patient, who was treated with radiation therapy, had biochemical recurrence. CONCLUSIONS: Deferred therapy may be a feasible alternative to curative treatment in select patients with favorable, localized prostate cancer. About half of these patients remain free of progression at 10 years and definitive treatment appeared effective in those with progression. Absent cancer on repeat needle biopsy identified cases highly unlikely to progress.

Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in human prostate.

BACKGROUND: The growth and dissemination of tumors has been associated with angiogenesis, which is regulated by a group of polypeptide factors including vascular endothelial growth factor-C (VEGF-C). VEGF-C binds its receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) to promote growth of tumor-associated lymphatic vessels. METHODS: In this study, microarray technology was used to build tissue arrays of normal prostate, benign prostate hyperplasia (BPH) and prostate carcinomas (PCa) using tissues from 640 patients. Slides were sectioned and stained with a polyclonal antibody to VEGFR-3 using a standard immunoperoxidase method and digitized. Immunoreactivity was scored using a 0-3+ semiquantitation scoring system for both intensity and percentage. The sum index was obtained by totaling the scores. RESULTS: VEGFR-3 is expressed in normal prostate, BPH, and PCa, but VEGFR-3 expression is up-regulated in PCa. We also found that VEGFR-3 is correlated with pre-operative prostate-specific antigen (Pre-PSA), Gleason score, and lymph node metastasis. The recurrence-free 5-year survival in cases with lower sum index (0-3) was significantly higher than that in cases with higher sum index (4-6) (77.3, 69.6%, respectively, P = 0.037) by Kaplan-Meier actuarial model. CONCLUSIONS: Our data suggest that VEGFR-3 expression is associated with tumor progression and may play an important role in facilitating lymphatic spread of PCa; high-level of VEGFR-3 expression in prostate cancer cells increases the risk of biochemical recurrence in prostate cancer patients treated by radical prostatectomy.

A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer.

PURPOSE: We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases. RESULTS: Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes. CONCLUSIONS: Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

Analysis of clinical stage T2 prostate cancer: do current subclassifications represent an improvement?

PURPOSE: The purpose of this study was to determine whether the extent of palpable cancer within the prostate predicts outcome after radical prostatectomy. PATIENTS AND METHODS: We combined prospectively collected data on 1,755 consecutive clinical stage T2 patients treated with radical prostatectomy alone at four institutions. According to the 1992 American Joint Committee on Cancer tumor-node-metastasis system, 645 (37%) were T2a, 758 (43%) were T2b, and 352 (20%) were T2c. Kaplan-Meier and proportional hazards regression analyses were performed on the 1992 and 1997 T2 subclassifications. After controlling for the effects of prostate-specific antigen (PSA) and biopsy Gleason sum, the two staging systems were compared for their ability to predict recurrence-free survival (RFS). Adjusted RFS curves were constructed using the corrected group prognosis method. RESULTS: Follow-up ranged from 1 to 166 months (median, 26 months). Cancer recurred in 417 (24%) of the T2 patients. The 1992 (P =.005) but not the 1997 (P =.100) T2 subclassification predicted outcome after controlling for PSA and Gleason sum. After covariate adjustment, RFS was 7% higher at 5 years in the 1992 T2a subcategory relative to the T2b subcategory. CONCLUSION: The 1992 American Joint Committee on Cancer system is superior to the 1997 system, and the former adds prognostic information to a model containing pretreatment PSA and Gleason sum. These results suggest that 1992 T2 subclassification derived from palpable findings improves prognostication over the 1997 subclassification.