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Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease-Specific Death: A Systematic Review and Meta-analysis.

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Abstract
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To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015. Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. A priori outcomes were recurrence, metastasis, and DSD. Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Significant risk factors for metastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32). Evidence quality was considered low to moderate. Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20 mm is associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.

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Relationship between Preoperative Pyuria and Bacille Calmette-Guerin Treatment in Intravesical Recurrence after Transurethral Resection of High-Risk, Non-Muscle Invasive, Bladder Carcinoma: A Retrospective Study of Human Data
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Simple SummarySome researchers have found that preoperative pyuria is a risk factor for the recurrence of high-risk non-muscle invasive bladder cancer. However, no one has determined the risks of pyuria in relation to bacille Calmette-Guerin (BCG) treatment status. We defined pyuria as ≥10 white blood cells per high-power field. We analyzed recurrence-free rates in 424 patients with high-risk non-muscle invasive bladder cancer who had and had not undergone BCG treatment. We identified no risk factors for recurrence in the BCG-treated group (n = 179). However, in the non-BCG treated group (n = 245), pyuria was associated with being female and having T1 cancer. According to univariate and multivariate analysis, preoperative pyuria is an independent risk factor for intravesical recurrence. No significant difference in the severity of pyuria was found between BCG and non-BCG-treated groups. Aggressive BCG treatment may need to be considered in patients with high-risk non-muscle invasive bladder cancer and pyuria.Some researchers have found that preoperative pyuria is a risk factor for recurrence after transurethral resection of high-risk non-muscle invasive bladder cancer. However, to our knowledge, none have clarified the risks associated with pyuria according to bacille Calmette-Guerin (BCG) treatment status. We retrospectively selected patients with high-risk non-muscle invasive bladder cancer according to Japanese Urological Association guidelines. Pyuria was defined as ≥10 white blood cells per high-powered field. We analyzed recurrence-free rates (RFS) in 424 patients who had and had not undergone BCG treatment. The median duration of follow-up was 45.2 months. According to multivariate analysis, postoperative intravesical BCG induction and preoperative pyuria were independent risk factors for intravesical recurrence in the whole study cohort. We found no significant risk factors for recurrence in the BCG-treated group (n = 179). In the non-BCG-treated group (n = 245), patients with pyuria were much more frequently female and more often had T1 disease than patients without pyuria. According to univariate and multivariate analysis, preoperative pyuria is an independent risk factor for intravesical recurrence. There was no significant difference in the severity of pyuria between the BCG and non-BCG-treated groups. Aggressive BCG treatment may need to be considered in patients with high-risk NMIBC and pyuria.

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