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JAMA Oncology Apr 2022Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and...
IMPORTANCE
Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.
OBJECTIVE
To develop recommendations for the care of adults with EMPD.
EVIDENCE REVIEW
A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.
FINDINGS
The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.
CONCLUSIONS AND RELEVANCE
Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.
Topics: Aged; Humans; Imiquimod; Paget Disease, Extramammary; Prospective Studies; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 35050310
DOI: 10.1001/jamaoncol.2021.7148 -
The Lancet. Digital Health Jun 2022Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically... (Review)
Review
Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation.
Topics: Algorithms; Artificial Intelligence; Early Detection of Cancer; Humans; Machine Learning; Primary Health Care; Skin Neoplasms
PubMed: 35623799
DOI: 10.1016/S2589-7500(22)00023-1 -
Annals of Oncology : Official Journal... Oct 2017Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand... (Review)
Review
BACKGROUND
Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class.
METHODS
Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR), χ2 tests and multivariable regression models were used to analyse for effect size and associations.
RESULTS
We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8-12.9), hypophysitis (OR 6.5, 95% CI 3.0-14.3) and rash (OR 2.0, 95% CI 1.8-2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2-12.7), hypothyroidism (OR 4.3, 95% CI 2.9-6.3), arthralgia (OR 3.5, 95% CI 2.6-4.8) and vitiligo (OR 3.5, 95% CI 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials [melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis.
DISCUSSION
CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; CTLA-4 Antigen; Clinical Trials as Topic; Humans; Immune System Diseases; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 28945858
DOI: 10.1093/annonc/mdx286 -
Journal of the American Academy of... Sep 2021Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results.
BACKGROUND
Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results.
OBJECTIVE
To systematically review the prevalence of dermoscopic structures in BCC and its subtypes.
METHODS
Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes.
RESULTS
Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC.
LIMITATIONS
Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions.
CONCLUSION
In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.
Topics: Carcinoma, Basal Cell; Dermoscopy; Humans; Pigmentation; Pigmentation Disorders; Skin Neoplasms
PubMed: 31706938
DOI: 10.1016/j.jaad.2019.11.008 -
JAMA Dermatology Apr 2016To 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... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
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.
OBJECTIVE
To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC.
DATA SOURCES
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.
STUDY SELECTION
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.
DATA EXTRACTION AND SYNTHESIS
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.
MAIN OUTCOMES AND MEASURES
A priori outcomes were recurrence, metastasis, and DSD.
RESULTS
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.
CONCLUSIONS AND RELEVANCE
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.
Topics: Carcinoma, Squamous Cell; Genetic Predisposition to Disease; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Risk Factors; Skin Neoplasms
PubMed: 26762219
DOI: 10.1001/jamadermatol.2015.4994 -
Journal of Cutaneous Medicine and... 2022Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
OBJECTIVE
To evaluate the effect of nicotinamide in prevention of skin cancers.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: "nicotinamide"; "randomized controlled trial" (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned .
RESULTS
We screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs.
CONCLUSION
Oral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemoprevention; Drug-Related Side Effects and Adverse Reactions; Humans; Keratosis, Actinic; Niacinamide; Skin Neoplasms
PubMed: 35134311
DOI: 10.1177/12034754221078201 -
Critical Reviews in Oncology/hematology Apr 2021Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence,... (Meta-Analysis)
Meta-Analysis Review
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence, severity, and spectrum (involving various specific adverse events) of each EGFR-TKI are of particular clinical interest and importance. Data from phase II and III randomized controlled trials comparing treatments among EGFR-TKIs (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib) and chemotherapy for lung cancer were synthesized with Bayesian network meta-analysis. The primary outcome was systemic all-grade and grade ≥3 adverse events. The secondary outcome was specific all-grade adverse events including those of the skin, gastrointestinal tract, lung, etc. 40 trials randomizing 13,352 patients were included. Generally greater toxicity for dacomitinib and afatinib, and safety for icotinib were suggested. Furthermore, we found individual EGFR-TKIs had different toxicity spectrums. These findings provide a compelling safety reference for the individualized use of EGFR-TKIs for patients with lung cancer.
Topics: Bayes Theorem; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Network Meta-Analysis; Protein Kinase Inhibitors
PubMed: 33757838
DOI: 10.1016/j.critrevonc.2021.103305 -
Clinics in Dermatology 2022Gel nail polish (GNP) has recently gained worldwide popularity. We have conducted a comprehensive summary of the complications of GNP through a literature search using...
Gel nail polish (GNP) has recently gained worldwide popularity. We have conducted a comprehensive summary of the complications of GNP through a literature search using the PubMed, Scopus, and Google Scholar databases to identify eligible contributions. Complications were divided into mechanical and traumatic nail disorders, allergic contact dermatitis (ACD), and ultraviolet (UV)-induced lesions. A total of 12 contributions were included, identifying 88 patients, all of whom were women. Six of the reports described ACD (62 cases, 70.5%), 3 concerned mechanical nail damage (23 cases, 26.1%), and 3 reported UV-induced skin lesions (3 cases, 3.4%). ACD developed an average of 30 months after GNP initiation. The most frequent culprit allergens were 2-hydroxypropyl methacrylate and 2-hydroxyethyl methacrylate. Pterygium inversum unguis was the most frequent mechanical lesion (n = 17). Squamous cell carcinoma was reported in 3 cases. The delay between UV exposure and the diagnosis of squamous cell carcinoma ranged from 11 to 15 years. Scant literature and a lack of education among consumers and beauticians have led to the uncontrolled use of GNP. The principle of managing nail cosmetic problems is prevention through education. There is a need for understanding the processes involved and the associated complications to facilitate appropriate treatment and safe use.
Topics: Humans; Female; Male; Patch Tests; Dermatitis, Allergic Contact; Cosmetics; Nails; Nail Diseases; Drug-Related Side Effects and Adverse Reactions; Carcinoma, Squamous Cell
PubMed: 35907576
DOI: 10.1016/j.clindermatol.2022.07.008 -
Radiotherapy and Oncology : Journal of... Oct 2017To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell... (Meta-Analysis)
Meta-Analysis
PURPOSE
To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs).
METHODS
A PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985-2016 evaluating patients with T1-2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β=3 (BEDs) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED and cosmetic outcomes.
RESULTS
A total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n=9255) or brachytherapy (n=474). Median follow-up was 36months (range: 12-77). Median dose was 45Gy/11 fractions (interquartile range: 37.5Gy/6-55Gy/18) at 4Gy/fraction (interquartile range: 2.5-6Gy); most hypofractionated 18.75Gy/1. There was a trend to decreased "good" cosmesis with higher total dose: -3.4% "good" cosmesis/10Gy BED, p=0.01. Similarly, there was a trend to increased "fair" cosmesis with higher dose: +3.8% "fair" cosmesis/10Gy BEDp=0.006. At a BED of 100Gy, the expected rate of "good" cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED. Fewer than 8% of patients experienced "poor" cosmesis, independent of dose or fractionation regimen.
CONCLUSION
Hypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in "good" cosmesis in 80% of patients.
Topics: Brachytherapy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Radiation Dose Hypofractionation; Skin Neoplasms
PubMed: 28843727
DOI: 10.1016/j.radonc.2017.08.011 -
The Cochrane Database of Systematic... Nov 2020Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non-surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.
OBJECTIVES
To assess the effects of interventions for BCC in immunocompetent adults.
SEARCH METHODS
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically-proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant- and observer-rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low-risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty-two studies were industry-funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies. Overall, surgical interventions have the lowest recurrence rates. For high-risk facial BCC (high-risk histological subtype or located in the facial 'H-zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low-certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low-certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post-operatively (one study; low-certainty evidence); however, no raw data were available for this outcome. When comparing imiquimod and SE for nBCC or sBCC at low-risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate-certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate-certainty evidence). There may be little to no difference in the number of participant-rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low-certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer-rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low-certainty evidence). Both cosmetic outcomes were measured at three years. Based on one study of 347 participants with high- and low-risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low-certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low-certainty evidence). Radiotherapy probably results in a smaller number of good participant- (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer-rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate-certainty evidence). Methyl-aminolevulinate (MAL)-PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low-risk nBCC in the head and neck area; low-certainty evidence). There were no useable data for measurement at five years. MAL-PDT probably results in greater numbers of participant- (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer-rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low-risk nBCC and sBCC; moderate-certainty evidence). Based on moderate-certainty evidence (single low-risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL-PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer-rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant-rated cosmetic outcomes were not measured for this comparison. AEs with surgical interventions include wound infections, graft necrosis and post-operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non-surgical interventions. Treatment-related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL-PDT.
AUTHORS' CONCLUSIONS
Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high-risk facial primary BCC (low-certainty evidence). Non-surgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non-surgical treatments, imiquimod has the best evidence to support its efficacy. Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer-term follow-up.
Topics: Adult; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma, Basal Cell; Cryotherapy; Female; Humans; Imiquimod; Immunocompetence; Laser Therapy; Male; Mohs Surgery; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Radiotherapy; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome
PubMed: 33202063
DOI: 10.1002/14651858.CD003412.pub3