Objective: We conducted this review to support the United States Preventive Services Task Force (USPSTF) in updating its 2016 recommendation on screening for skin cancer. The objective was to review benefits and harms of routine skin cancer screening in asymptomatic screening populations aged ≥15 years.
Data Sources: We searched MEDLINE ALL via Ovid, Embase via Elsevier, and the Cochrane Central Register of Controlled Trials via Wiley. We updated the search used in the 2016 systematic review on January 12, 2021, and we ran a bridge search on January 7, 2022. A research librarian developed and executed the search strategy. Studies included in the prior review to support the 2016 recommendation and studies referenced in recently published reviews were also considered for inclusion.
Study Selection: We reviewed 20,320 abstracts and 522 full-text articles against prespecified inclusion criteria. Eligible studies were English-language randomized controlled trials (RCTs), controlled clinical trials, nonrandomized studies with contemporaneous controls reporting morbidity or mortality associated with skin cancer, or all-cause mortality, stage or lesion thickness at detection of skin cancer or precancerous lesions, and harms of skin cancer screening. At least two investigators independently critically appraised all studies. Data were extracted by one investigator and checked for accuracy by a second.
Data Analysis: We extracted relevant study details and outcomes from fair- or good-quality studies. We provided narrative synthesis of results and used summary tables to facilitate comparisons across studies. The overall strength of evidence was graded as high, moderate, low, or insufficient based on criteria adapted from the Evidence-based Practice Center (EPC) Program.
Results: We included three studies (10 articles, n=NR in one study; 1,791,615 in the other two) on the direct benefits of skin cancer screening and two studies (3 articles, n=232) on persistent harms of skin cancer screening. We included six studies (7 articles, n=2,947,595) on the association between routine clinician skin examination and stage or lesion thickness at skin cancer detection. We included nine studies (9 articles, n=l,326,051) on the association between stage at skin cancer detection and melanoma or all-cause mortality. Seventeen studies were newly identified in this update.
Direct evidence on effectiveness of skin cancer screening. Three non-randomized studies (one good-quality; two fair-quality) evaluated the association between melanoma mortality and skin cancer screening over 4 to 10 years followup. At 10-years of followup of the Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany (SCREEN) study, population melanoma mortality rates in the SCREEN region compared to the rest of Germany suggest no mortality benefit to routine skin cancer screening. Similarly, at 5-year followup of the German National Screening Program, no mortality benefit was observed based on national population statistics. One non-randomized study of melanoma mortality in individuals with documented skin cancer screening provided through German statutory health insurance found an absolute decrease in mortality suggesting a screening benefit at four-year followup, but this difference was attenuated on multivariate analysis and adjustment for lead time bias. No included studies reported all-cause mortality, skin squamous cell carcinoma mortality, basal cell carcinoma mortality, or skin cancer morbidity.
Harms. Evidence on the persistent psychosocial or cosmetic harms of screening was minimal. In a fair-quality study conducted in Germany (n=45), 27 patients rated 7 percent (4 out of 56) of shave biopsy sites having poor cosmetic outcomes at 6-month followup. A fair-quality United States study (n=187) that assessed psychological wellbeing at 5 and 8 months after skin cancer examination by trained primary care providers found that participants scored within the normal range on measures of anxiety and depression, with none to minimal psychological impacts of screening. Overdiagnosis and subsequent overtreatment of early-stage melanoma is a potential harm of skin cancer screening based on population incidence rates, but no direct evidence was available.
Indirect evidence: association between routine clinician skin examination and stage or thickness at skin cancer detection. Based on data from four fair-quality evaluations of three skin cancer screening programs (n=2,344,210), and one good-quality physician-focused skin examination initiative (n=595,799), routine clinician skin examination is not associated with increased detection of keratinocyte carcinoma, melanoma, or skin cancer precursor lesions compared to usual care or lesion-directed examination. Similarly, routine skin examination is not associated with stage at detection for invasive melanoma. Evidence is inconsistent on whether clinician skin examination is associated with higher detection of in situ melanoma based on two studies (n=2,530 melanoma cases), or with thinner lesions (<1mm or <2mm) at melanoma detection based on three studies (n=6,133 melanoma cases).
Indirect evidence: association between stage at skin cancer detection and melanoma mortality or all-cause mortality. Three nonrandomized studies (two good-quality, one fair-quality; n=407,133) reported melanoma-specific mortality, and three nonrandomized studies (one good-quality, 2 fair-quality; n=473,660) reported all-cause mortality. Later stage at detection was consistently associated with increased risk of melanoma mortality. Compared to in situ disease at detection, adjusted hazard ratios for melanoma mortality were 5.8 (95% CI, 5.3 to 6.3) for localized, 31.5 (95% CI, 28.9 to 34.2) for regional, and 169.6 (95% CI, 154.2 to 186.6) for distant stage in one U.S.-based study (n=185,219). Two studies using localized stage at detection as the referent group found a similar pattern of increasing melanoma mortality risk with increasing stage. No included studies evaluated the association between stage at diagnosis and skin cancer morbidity.
In two nonrandomized studies (1 good-quality, 1 fair-quality; n=135,490), melanoma mortality was higher for males than for females. Three studies with overlapping populations (n=708,814) examined melanoma mortality risk for specific racial and ethnic groups. One study found similar odds of melanoma mortality risk for White and Black persons within each stage at detection. In two other studies with overlapping populations, melanoma mortality risk was higher among Black, Asian American, Native American, Pacific Islanders (AANAPI), and Hispanic adults with melanoma AJCC Stage I and SEER localized stages compared to White adults. In one of these studies, the risk for melanoma mortality among Hispanic persons with regional or distant melanoma stage was also higher than among White adults.
Regarding all-cause mortality, the same pattern was observed over three large nonrandomized studies. In one study (n=185,219), the risk for all-cause mortality was adjHR 1.5 (95% CI, 1.5 to 1.5) for localized, 3.9 (95% CI, 3.8 to 4.1) for regional, 15.8 (95% CI, 14.9 to 16.7) for distant disease, compared to in situ melanoma at detection.
No included studies addressed keratinocyte carcinoma mortality by stage at detection.
Limitations: The body of evidence for benefits and harms of screening is small and derived from nonrandomized studies primarily conducted outside of the United States. The applicability to United States primary care settings might be low.
Conclusions: A substantial observational evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, ecological studies suggest no melanoma mortality benefit associated with skin cancer screening in adolescents or adults in regions with implemented routine screening compared to regions without routine screening. Nonrandomized evidence suggests no association between routine clinician skin examination and earlier stage at melanoma detection; evidence is inconsistent on whether clinician skin examination is associated with thinner melanoma lesions at detection. There is little direct evidence on harms of screening, however; other than overdiagnosis and overtreatment, there are few hypothesized serious harms.