Adjuvant Radiation Therapy After Radical Nephrectomy in Patients with Localized Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

CONTEXT: Adjuvant radiation therapy has been recommended for patients at higher risk of relapse from renal cell carcinoma (RCC) to improve disease-free survival (DFS) and overall survival (OS) after radical nephrectomy. OBJECTIVE: To quantify the benefit of adjuvant radiation therapy. EVIDENCE ACQUISITION: A systematic review of electronic databases identified publications exploring the association between adjuvant radiation therapy and locoregional recurrence (LRR), DFS, and OS among patients after radical nephrectomy for early-stage RCC. Hazard ratios for DFS were weighted and pooled using the generic inverse variance and random effects model. Odds ratios for LRR, DFS, and OS at 5yr were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effects modeling. EVIDENCE SYNTHESIS: Twelve studies comprising 1624 patients were included in the analysis. Ten studies were retrospective and two were randomized controlled trials. Adjuvant radiation therapy was delivered to 37% of patients. The median follow-up was 49mo. Adjuvant radiation therapy was not associated with better DFS or OS at 5yr, but was associated with less LRR. CONCLUSIONS: With the caveat that confounding by indication may result from pooling data from predominantly nonrandomized studies, adjuvant radiation after radical nephrectomy was not associated with improved DFS or OS but was associated with less LRR. PATIENT SUMMARY: Radiation therapy after resection of renal cell carcinoma with a high risk of relapse may reduce the risk of local recurrence but not the risk of disease recurrence or death after 5yr.

Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis.

BACKGROUND: The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown. METHODS: A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes [disease-free (DFS) and, overall survival (OS)] in women with early breast cancer. The hazard ratios (HR) for DFS and OS were weighted and pooled in a meta-analysis using generic inverse variance and random effects modeling. RESULTS: Fifty-three studies comprising 21,418 women were included. EGFR-overexpression was found in 27% of the patients. Primary analysis included studies reporting HRs from multivariable analyses (10 studies including 4857 patients with HRs for OS and 17 studies comprising 8747 patients with HRs for DFS), EGFR-overexpression was associated with worse OS (HR 1.98, 95% CI: 1.59-2.47, p < .001) and DFS (HR 1.59, 95% CI 1.30-1.95, p < .001). The influence of EGFR overexpression on DFS was greater in women with triple negative tumors compared to women with non-triple negative tumors (HR 2.35 versus HR 1.45, respectively; p = .01). Analysis looking at odd ratios for both 5-year and 10-year for DFS and OS showed similar results. CONCLUSION: EGFR-overexpression appears to be associated with reduced OS and DFS in women with early breast cancer. Patients with triple negative and EGFR-overexpression have poorer OS and DFS than those with triple negative tumors and normal EGFR expression.

Prognostic role of Ki-67 score in localized prostate cancer: A systematic review and meta-analysis.

BACKGROUND: Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically. METHODS: Medline and EMBASE databases were searched without date or language restrictions, using "KI67" and "prostate cancer" MeSH terms. Studies reporting Ki-67 association with clinical outcomes (disease-free survival [DFS], biochemical failure-free survival, rate of distant metastases [DM], disease-specific survival [DSS], or overall survival [OS], or all of these) in patients with PCa managed actively were included, and relevant data extracted by 2 independent reviewers. Odds ratios (OR) were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effect modeling. RESULTS: Twenty-one studies comprising 5,419 patients met eligibility for analysis, and 67.6% of patients had low Ki-67. Mean Ki-67 was 6.14%. High Ki-67 was strongly associated with worse clinical outcomes. DFS was better in those patients with low Ki-67 at 5 and 10 years (OR = 0.32, 95% CI: 0.23-0.44, P<0.00001; OR = 0.31, 95% CI: 0.20-0.48, P<0.00001). Similarly, low Ki-67 was related to improved DSS at 5 and 10 years (OR = 0.15, 95% CI: 0.10-0.21, P<0.00001; OR = 0.16, 95% CI: 0.06-0.40, P<0.00001). Association between low Ki-67 scores with improved OS (OR = 0.47; 95% CI: 0.37-0.61; P<0.00001) and high Ki-67 scores with DM at 5 years (OR = 4.07; 95% CI: 2.52-6.58; P<0.00001) was consistently observed. CONCLUSIONS: High Ki-67 expression in localized PCa is a factor of poor prognosis for DSS, biochemical failure-free survival, DFS, DM, and OS after curative-intent treatments. Incorporation into clinical routine of this widely available and standardized biomarker should be strongly considered.