Assessment of early continence recovery after radical prostatectomy: patient reported symptoms and impairment.

PURPOSE: Patients considering radical prostatectomy often inquire as to when they can expect to regain urinary continence. However, there is a paucity of patient self-reported data regarding the recovery of continence during the initial 3 months after surgery. Our objectives were to assess urinary continence changes early in the postoperative period and determine which of 2 commonly used definitions of continence more closely relate to patient reported urinary impairment. MATERIALS AND METHODS: A prospective study of 90 men with clinically localized prostate cancer who selected radical prostatectomy as primary therapy was conducted. Repeated measures of urinary continence as defined by 1) total urinary control, 2) the use of 1 or 0 pads daily, and 3) small or no problem with urinary function were obtained with a brief survey preoperatively and postoperatively. RESULTS: At 56 days after removal of urethral catheters, the actuarial rates of urinary continence recovery based on definitions 1 to 3 were 43%, 84% and 82%, respectively. The use of definition 2 for continence resulted in a 1.9 times higher actuarial rate for continence recovery when compared to definition 1 at 56 days (p <0.001). However, strong agreement was observed between definitions 2 and 3 (kappa = 0.69). CONCLUSIONS: Urinary control is recovered in a significant proportion of men who undergo radical prostatectomy during the initial 3 months. Continence rates will vary significantly based on the use of alternative definitions. The clinical practice of asking patients how many pads daily they use may be valid, as it corresponds well to the impairment they have.

Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate.

An essential event in the progression of adenocarcinoma is the loss of organized epithelial attachment (both to the basement membrane and to adjoining epithelial cells). The E-cadherin cell adhesion molecule has an established function in maintaining normal phenotype and tissue homeostasis, and loss of E-cadherin function has been implicated in tumorigenesis. Aberrations in E-cadherin are associated with prostate cancer progression; however, these aberrations are not simply a result of prodigious allelic loss. We have previously demonstrated a novel posttranslational truncation within the cytosolic domain of native Mr 120,000 E-cadherin to a membrane-bound Mr 97,000 species. We hypothesize that truncation of E-cadherin is an inactivating event that is significantly increased in localized prostate tumors and that it represents a novel molecular event that may distinguish prostate cancer from adjacent normal tissue. E-cadherin was characterized by Western blot analysis in matched normal and cancer tissue from 18 prostate cancer patients. Imaging and densitometry software were used to quantify the truncation of E-cadherin by measuring the ratio of Mr 97,000 E-cadherin to Mr 120,000 E-cadherin, which was significantly increased in the tumor aspect of the prostate gland. Herein, we report the first experiment comparing case-matched human normal and cancerous prostate tissue in the context of E-cadherin truncation.

Truncation of the beta-catenin binding domain of E-cadherin precedes epithelial apoptosis during prostate and mammary involution.

A potential target of hormone action during prostate and mammary involution is the intercellular junction of adjacent secretory epithelium. This is supported by the long-standing observation that one of the first visible stages of prostate and mammary involution is the disruption of interepithelial adhesion prior to the onset of apoptosis. In a previous study addressing this aspect of involution, we acquired compelling evidence indicating that the disruption of E-cadherin-dependent adhesion initiates apoptotic programs during prostate and mammary involution. In cultured prostate and mammary epithelial cells, inhibition of E-cadherin-dependent aggregation resulted in cell death following apoptotic stimuli. Loss of cell-cell adhesion in the nonaggregated population appeared to result from the rapid truncation within the cytosolic domain of the mature, 120-kDa species of E-cadherin (E-cad(120)). Immunoprecipitations from cell culture and involuting mammary gland demonstrated that this truncation removed the beta-catenin binding domain from the cytoplasmic tail of E-cadherin, resulting in a non-beta-catenin binding, membrane-bound 97-kDa species (E-cad(97)) and a free cytoplasmic 35-kDa form (E-cad(35)) that is bound to beta-catenin. Examination of E-cadherin expression and cellular distribution during prostate and mammary involution revealed a dramatic reduction in junctional membrane staining that correlated with a similar reduction in E-cad(120) and accumulation of E-cad(97) and E-cad(35). The observation that E-cadherin was truncated during involution suggested that hormone depletion activated the same apoptotic pathway in vivo as observed in vitro. Based on these findings, we hypothesize that truncation of E-cadherin results in the loss of beta-catenin binding and cellular dissociation that may signal epithelial apoptosis during prostate and mammary involution. Thus, E-cadherin may be central to homeostatic regulation in these tissues by coordinating adhesion-dependent survival and dissociation-induced apoptosis.