Thomson Jason, Hogan Sarah, Leonardi-Bee Jo, Williams Hywel C, Bath-Hextall Fiona J
Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK.
Centre for Evidence Based Healthcare, Division of Epidemiology and Public Health, Clinical Sciences Building Phase 2, University of Nottingham, Nottingham, UK.
Cochrane Database Syst Rev. 2020 Nov 17;11(11):CD003412. doi: 10.1002/14651858.CD003412.pub3.
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.
To assess the effects of interventions for BCC in immunocompetent adults.
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
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.
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.
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.
基底细胞癌（BCC）是影响白种人的最常见癌症，且全球发病率正在上升。虽然BCC很少致命，但会导致严重的发病率和成本。一线治疗通常是手术切除，但也有其他选择。新发表的研究和非手术治疗的发展意味着及时更新我们的Cochrane系统评价（首次发表于2003年，之前于2007年更新）是必要的。
评估免疫功能正常的成年人中BCC干预措施的效果。
我们将以下数据库的检索更新至2019年11月：Cochrane皮肤组专业注册库、CENTRAL、MEDLINE、Embase、CINAHL和LILACS。
对免疫功能正常的成年人中经组织学证实的原发性BCC进行干预的随机对照试验（RCT）。合格的对照为安慰剂、积极治疗、其他治疗或不治疗。
我们采用了Cochrane预期的标准方法程序。主要结局指标为三年和五年时的复发率（临床测量）（如果三年或五年时未进行测量，则纳入这些时间点之外的复发数据）以及参与者和观察者评定的良好/优秀美容效果。次要结局包括治疗期间和治疗后的疼痛、六个月内的早期治疗失败以及不良反应（AE）。我们使用GRADE评估每个结局的证据确定性。
本次更新纳入了52项RCT（26项新研究），涉及6690名参与者（中位数89名）。所有研究均来自二级护理门诊。纳入的男性多于女性。研究持续时间从六周至10年不等（平均13个月）。大多数研究（48/52）仅纳入低风险BCC（浅表型（sBCC）和结节型（nBCC）组织学亚型）。大多数领域的大多数研究存在低或不明确的偏倚风险。22项研究由行业资助：商业赞助商开展了大多数评估咪喹莫特的研究，以及近一半的光动力疗法（PDT）研究。总体而言，手术干预的复发率最低。对于高风险面部BCC（高风险组织学亚型或位于面部“H区”或两者皆有），与手术切除（SE）相比，莫氏显微外科手术（MMS）在三年时的复发率可能略低（分别为1.9%和2.9%）（风险比（RR）0.64，95%置信区间（CI）0.16至2.64；1项研究，331名参与者；低确定性证据），五年时（分别为3.2%和5.2%）（RR 0.61，95%CI 0.18至2.04；1项研究，259名参与者；低确定性证据）。然而，95%CI也包括复发风险增加和治疗之间无差异的可能性。术后18个月，参与者和观察者判断MMS和SE在美容效果改善方面可能几乎没有差异（1项研究；低确定性证据）；然而，该结局没有原始数据。在低风险部位比较nBCC或sBCC的咪喹莫特和SE时，咪喹莫特在三年时的复发率可能高于SE（分别为16.4%和1.6%）（RR 10.30，95%CI 3.22至32.94；1项研究，401名参与者；中等确定性证据），五年时（分别为17.5%和2.3%）（RR 7.73，95%CI 2.81至21.3；1项研究，383名参与者；中等确定性证据）。参与者评定的良好/优秀美容效果数量可能几乎没有差异（RR 1.00，95%CI 0.94至1.06；1项研究，326名参与者；低确定性证据）。然而，观察者评定时，咪喹莫特可能比SE产生更多的良好/优秀美容效果（分别为60.6%和35.6%）（RR 1.70，95%CI 1.35至2.15；1项研究，344名参与者；低确定性证据）。两种美容效果均在三年时测量。基于一项对347名面部高风险和低风险原发性BCC参与者的研究，与冷冻切片边缘控制下的SE相比，放疗在三年时的复发率可能更高（分别为5.2%和0%）（RR 19.11，95%CI 1.12至325.78；低确定性证据），四年时（分别为6.4%和0.6%）（RR 11.06，95%CI 1.44至84.77；低确定性证据）。四年时测量，放疗可能导致参与者评定的良好/优秀美容效果数量（RR 0.76，95%CI 0.63至0.91；分别为50.3%和66.1%）或观察者评定的数量（RR 0.48，95%CI 0.37至0.62；分别为28.9%和60.3%）低于SE（均为中等确定性证据），此时可能出现色素沉着异常和毛细血管扩张。与SE相比，甲基氨基酮戊酸（MAL）-PDT在三年时的复发率可能更高（分别为36.4%和0%）（RR 26.47，95%CI 1.63至429.92；1项研究；68名头颈部低风险nBCC参与者；低确定性证据）。五年时没有可用的测量数据。与SE相比，MAL-PDT在一年时可能导致更多参与者评定的（RR 1.18，95%CI 1.09至1.27；97.3%对82.5%）或观察者评定的（RR 1.87，95%CI 1.54至2.26；87.1%对46.6%）良好/优秀美容效果（2项研究，309名低风险nBCC和sBCC参与者；中等确定性证据）。基于中等确定性证据（单一低风险sBCC），与MAL-PDT相比，咪喹莫特在三年时的复发率可能更低（分别为22.8%和51.6%）（RR 0.44，95%CI 0.32至0.62；277名参与者），五年时（分别为28.6%和68.6%）（RR 0.42，95%CI 0.31至0.57；228名参与者）。一年时观察者评定的良好/优秀美容效果数量可能几乎没有差异（RR 0.98，95%CI 0.84至1.
