Context. In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological patient outcomes. Objective. To perform a systematic review of the existing literature on BCR after treatment with curative intent for non-metastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic features in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies (QUIPS) tool. Both a narrative synthesis and meta-analysis were undertaken. Evidence synthesis. Overall, 77 studies were included for analysis, of which 14 studies addressed objective 1, recruiting 20406 patients. Objective 2 was addressed by 71 studies with 29057, 11301 and 4272 patients undergoing RP, RT or a mixed population (mix of patients undergoing RP or RT as primary treatment) respectively. There was low risk of bias for study participation, confounders and statistical analysis. For most studies, attrition bias, prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with a short PSA Doubling Time (PSA-DT) and high final Gleason score after RP or a short Interval to Biochemical Failure (IBF) after RT and high biopsy Gleason score. Conclusion. BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. A short PSA-DT and high final Gleason score after RP and a short IBF after RT and high biopsy Gleason score are the main factors which have a negative impact on survival. Patient summary. This review looks at the risk of dying in men who have a rising PSA blood test after curative surgery or radiotherapy. For many men a rising PSA does not mean they are at a higher risk of dying from prostate cancer in the longer term. Men with a PSA that rises shortly after they were treated with radiotherapy or a rapidly rising PSA after surgery and a high tumor-grade for both treatment modalities are at the highest risk of dying.
A mouse monoclonal antibody against the N-terminal region of human androgen receptor (AR) was used to identify receptors by immunoperoxidase staining in frozen serial sections of skin from scalp, face, limb and genitalia of men and women aged 30-80 years. AR staining was restricted to cell nuclei. In sebaceous glands, AR were identified in basal and differentiating sebocytes. The percentage of receptor-positive basal sebocyte nuclei in the temple/forehead region was greater in males (65%) than in females (29%). AR staining was restricted to the cells of dermal papillae in anagen and telogen hair follicles. The percentage of dermal papillae containing AR was greater in males (58%) than in females (20%). The number of positively stained dermal papillae was lowest in female scalp skin. In 163 hair follicles sectioned, AR were absent from germinative matrix, outer root sheath (including the bulge region), inner root sheath, hair shaft and hair bulb, and from the capillaries present in some large dermal papillae. AR were present in pilosebaceous duct keratinocytes, suggesting that androgens may influence pilosebaceous duct keratinization. AR were also identified in interfollicular epidermal keratinocytes and dermal fibroblasts although, in both cell types, intensity and frequency of staining were greatest in genital skin. AR were identified in luminal epithelial cells of apocrine glands in genital skin and in certain cells of the secretory coils of eccrine sweat glands in all body sites. This study indicates that androgens regulate sebaceous gland and hair growth by acting upon two different types of target cells, the epithelial sebocytes of sebaceous glands and the mesenchymal cells of the hair follicle dermal papilla.(ABSTRACT TRUNCATED AT 250 WORDS)
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