https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)09408-4.pdf

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

The introduction of an effective blood test, prostate specific antigen (PSA), has made it possible to diagnose more and more men in an earlier stage where they can be offered potentially curative treatments. The other side of the coin is that if effective diagnostic procedures are used unselectively in elderly men with a short life expectancy, a problem with over diagnosis and over treatment might occur. Thus the same stage of prostate cancer may need different treatment strategies, pending on the patient’s life expectancy. This, and many other issues regarding the disease, is the subject of the EAU guidelines on prostate cancer. G UI DE LI N ES O N P RO ST AT E CA N CE R 10

/pdf/guidelines-on-prostate-cancer-xdnunn4th8.pdf

Guidelines on Prostate Cancer

Purpose: To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. Methods and Materials: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2–T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. Results: As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival=PSA p p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2–6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7–10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival. Conclusion: In patients with Gleason score 2–6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate

Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 in localized human prostate cancer. Archival material from 113 radical prostatectomy specimens obtained between 1985 and 1993 was stained immunohistochemically for p27Kip1 protein using a commercially available antibody. Patient charts were reviewed for preoperative serum prostate-specific antigen, clinical and pathological staging, Gleason tumor grade, time to biochemical and clinical recurrence, and survival. Strong p27Kip1 staining was uniformly seen in benign prostatic epithelial components in all tumor sections. p27Kip1 staining was reduced in most prostate cancers and was variable in prostatic intraepithelial neoplasia. Decreased p27Kip1 staining (<25% of nuclei stained positive for p27Kip1) correlated with seminal vesicle involvement (P = 0.0032) and with higher Gleason grade (P = 0.0114). On univariate analysis, low p27Kip1 predicted an increased risk of treatment failure in the node-negative cohort (P = 0.0037) and in the subset who did not receive neoadjuvant hormonal therapy (P = 0.049). Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047). Seminal vesicle involvement (P = 0.034) and positive surgical margins (P = 0.047) were also independent prognostic factors for disease recurrence. In patients who received preoperative neoadjuvant hormonal therapy, low p27Kip1 in the pathological specimen was an even stronger predictor of outcome than it was in the entire group (n = 23, P = 0.015).

/pdf/loss-of-cyclin-dependent-kinase-inhibitor-p27kip1-is-a-novel-2mktpnow92.pdf

Loss of Cyclin-dependent Kinase Inhibitor p27Kip1 Is a Novel Prognostic Factor in Localized Human Prostate Adenocarcinoma

Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockage in Clinical Stage B2 (T2bNxM0) Prostate Cancer

Zev Wajsman

Papers

Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockage in Clinical Stage B2 (T2bNxM0) Prostate Cancer