Extraprostatic Extension into Periprostatic Fat is a More Important Determinant of Prostate Cancer Recurrence than an Invasive Phenotype

Purpose: Although micrometastasis development correlates closely with the depth of invasion of many tumor types, it is unclear whether invasion into but not through the prostatic pseudocapsule has a negative impact on prognosis, similar to extraprostatic extension. We defined the impact of pseudocapsular invasion on the risk of post-prostatectomy biochemical recurrence. Materials and Methods: Patients with pT2-3a prostate cancer were identified from a prospectively recorded database. Those with pT2 disease were categorized according to pseudocapsular invasion presence or absence. The impact of pseudocapsular invasion on biochemical recurrence was determined by univariable and multivariable Cox regression analysis. Results: In a cohort of 1,338 patients we identified 595 with organ confined cancer positive for pseudocapsular invasion. Compared to tumors without evidence of invasion, pseudocapsular invasion was positively associated with higher Gleason grade and tumor volume (1.2 vs 1.9 cc, each p < 0.001). On univariable analysis there was no difference in biochemical recurrence-free survival between patients with vs without pseudocapsular invasion, although those with extraprostatic extension had significantly lower biochemical recurrence-free survival (p < 0.001). This was confirmed on multivariable analysis, which revealed that extraprostatic extension was a significant independent predictor of biochemical recurrence (HR 1.53, p = 0.018). The presence of pseudocapsular invasion had no effect (HR 0.81, p = 0.33). Conclusions: Pseudocapsular invasion is not a pathological feature associated with an adverse outcome after prostatectomy. Thus, the depth of tumor invasion is not a continuum of risk and access to periprostatic adipose tissue is a more important determinant of disease behavior than an invasive phenotype.