Mistaken Conclusions in a Nonmelanoma Skin Cancer Article Published in JAMA JOSEPH F. SOBANKO, MD,*†
STEVEN T. ROSS, MA‡
he recently published, Treatment of Nonfatal Conditions at the End of Life: Nonmelanoma Skin Cancer, by Linos and colleagues addresses the management of basal and squamous cell carcinomas at two dermatology clinics in Northern California.1 In this article, an emphasis is placed on determining whether nonmelanoma skin cancer (NMSC) is managed differently in patients with limited life expectancy (LLE) than in healthier and younger patients. The authors justify this approach because there is a current paucity of data investigating whether patient age or functional status influences NMSC treatment decisions and patient outcomes. Based on the results of this study, respected commenting authors have concluded that “treatment of nonmelanoma skin cancer seems not to be provided in ways that best link burden of treatment with a patient’s underlying condition” and further describe Mohs micrographic surgery as “the most burdensome available treatment.”2 Unfortunately, there are numerous weaknesses and omissions that undermine the validity of Linos and colleagues’ report and may lead to misconceptions regarding skin cancer management, particularly in healthcare workers who do not manage such patients. It is imperative that this study’s weaknesses be highlighted so that the medical community at large can begin a frank dialogue on how to best manage the care of patients with NMSC.
In this prospective cohort study, 1,536 patients with NMSC were recruited over a 1-year period and then followed for a decade after enrollment. Analyzed outcomes were treatment patterns, tumor recurrence, mortality, and complications. In the 1,360 patients included, 68.7% of tumors were treated using Mohs surgery or traditional surgical excision, 26.7% were treated using a destructive modality (e.g., cryotherapy, electrodesiccation and curettage, laser), and 3.1% received no treatment. Although many claims are made from these data, the following commentary will focus on two divisive conclusions: Linos and colleagues’ data reveal that patients aged 85 and older or with a LLE (Charlson Comorbidity Index (CCI) ≥ 3) received an amount of surgical treatment for NMSC similar to that of younger and healthier patients, and one in five patients with LLE (and 15% of patients overall) reported “complications” of therapy. Even after univariate and multivariate models adjusted for tumor and patient characteristics, data analysis by Linos and colleagues demonstrates that surgical treatment of NMSC was performed independent of patient prognosis. Taken at face value, this finding implies that practitioners could be selecting surgical treatments without considering individual patient preferences or other important factors such as safety. In fact, the framework of this
*Division of Dermatologic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; †Edwin and Fannie Gray Hall Center for Human Appearance, University of Pennsylvania, Philadelphia, Pennsylvania; ‡Sage Analytical Sciences Group, Raleigh, Pennsylvania © 2014 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:489–496 DOI: 10.1111/dsu.12469 489
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article leads the reader to believe that surgical treatment of NMSC rivals the risk and effect that other surgical procedures such as cardiac surgery may have on patients, particularly elderly adults and those with multiple comorbidities. Findings by Kwok and colleagues3 are referenced, stating that 30% of patients underwent surgery in the last year of life, and almost 20% underwent a procedure in the last month of life. The authors fail to reveal that this particular study is specific to inpatient surgical procedures performed on elderly and frail adults. The public must be informed that NMSC surgery (Mohs or traditional excision performed under local anesthesia) in no way competes with the intensity or risk of these other inpatient surgical procedures performed while the patient is intubated and under general anesthesia. More than 90% of NMSC treatment occurs in a physician’s office rather than in a hospital or ambulatory surgical center.4 Myriad studies have demonstrated that outpatient surgical procedures, particularly Mohs surgery, are safe because of the elimination of general anesthesia and other risks inherent to inpatient surgical management.5–15 The most recent of these studies analyzed more than 20,000 Mohs procedures at 23 different centers and found an exceedingly low rate of serious adverse events (0.02%) and no deaths.16 Prudent use of procedures in patients near death is an irrefutable principle, as is shared decision-making for choosing a course of medical care. Not all NMSCs require surgical management. Patients with severe illness and multiple comorbidities may be poor surgical candidates, even in the outpatient setting, and require alternative approaches to their NMSC. In this study’s analysis, patients aged 85 and older or with a CCI of 3 or greater were considered to have a LLE. The fact that 43% of the LLE cohort died within 5 years (none of NMSC) substantiates this concept of shortened life. It is easy for the media to misconstrue these facts and extrapolate that “we are treating tumors, not patients,”17 but closer inspection of the authors’ definition of “LLE” reveals that one of their conclusions demands further attention.
The CCI is a tool that attempts to predict 10-year mortality of patients by adding a score that is assigned to various medical comorbidities; the higher the score, the worse the prognosis.18 (All readers are referred to the end of this commentary to understand how various comorbidities are scored.) Charlson herself updated the original CCI, stating that combining age and comorbidities into a single score better predicts patient prognosis for studies that involve more than 1–2 years of follow-up, which should apply to the study in question.19 With this new CCI, a patient older than 61, a 51-year-old with a history of peptic ulcer disease, a 55-year-old with a history of a myocardial infarction (MI), a 41-year-old with Hodgkin’s lymphoma, and a 45-year-old with moderate renal disease would meet the criteria for a CCI of 3. In all five of these clinical scenarios, 10-year survival for these patients is 77.5%.20 Table 1 in Linos and colleagues shows that the median CCI for patients who did not reach LLE criteria was 0.0 (interquartile range (IQR) 0.0–1.0). The median age of patients in the non-LLE treatment group was 63.0 (IQR 52.0–74.0). Three quarters of patients in this cohort were aged 52 and older, half were aged 63 and older, and one-quarter were aged 74 and older, yet the CCI for 75% of these patients was 1 or less. The CCI statistics as calculated do not include age or do not factor in age, as the index was designed (with 1 point added for each decade of life). The authors indicate that an age cutoff was used (85), although it is unclear why this, separate from the validated CCI definition, is used. This distinction appears to result in a lower CCI for patients aged 50–84 with few comorbidities and subsequent placement in the non-LLE arm rather than the LLE arm. One would expect this to result in greater disparity between the treatment groups for any analyses using these categorizations. Also, 492 patients, more than one-third of the overall cohort, did not have a tabulated CCI. The absence of this categorization for such a large part of this population should raise questions as to how different these patients were from those in the LLE and non-LLE
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TABLE 1. Charlson Comorbidity Index Scoring System Score
Myocardial infarction (history, not ECG changes only) Congestive heart failure Peripheral vascular disease (includes aortic aneurysm >6 cm) Cerebrovascular disease: CVA with mild or no residua or TIA Dementia Chronic pulmonary disease Connective tissue disease Peptic ulcer disease Mild liver disease (without portal hypertension, includes chronic hepatitis) Diabetes without end-organ damage (excludes diet-controlled alone) Hemiplegia Ivl ode rate or severe renal disease Diabetes with end-organ damage (retinopathy, neuropathy, nephropathy, or brittle diabetes) Tumor without metastases (exclude if >5 year from diagnosis) Leukemia (acute or chronic) Lymphoma Moderate or severe liver disease Metastatic solid tumor AIDS (not just HIV positive)
For each decade >40 years of age, a score of 1 is added to the above score. Abbreviations: ECG, electrocardiogram; CVA, cerebrovascular accident; TIA, transient ischemic attack; AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.
groups and regarding the inherent risk of comparing the overall cohort with those with an LLE categorization. In at least one reported result, this skew is apparent. Patient-reported complication rate (Table 2 in Ref ) is shown to be widely disparate (much lower) from those with CCI categorizations, fully 10 points lower than that of the non-LLE group and more than five points lower than that of the LLE group. Although it is curious that patients with LLE reported fewer complications than those in the nonLLE group, perhaps the greater question is why patients with an LLE categorization report far more complications than those without.
Aside from the methodologic aspects of assigning CCI, practical considerations also weaken the authors’ results. Presuming that age was not factored into the authors’ CCI calculation (using the older CCI), a patient would need more comorbidities to reach a CCI of 3 (e.g., history of MI + history of peptic ulcer disease + history of connective tissue disease), but the authors analyze the LLE arm of data by combining all patients with a CCI of 3 or more together. It stands to reason that the health and surgical risk of a patient with a CCI of 3 varies markedly from a patient with a CCI of 6 (e.g., a patient with AIDS). The 12-month mortality of a patient with a CCI of 3 is 19.3%, compared with 37% in the patient with a CCI of 6. If the authors wish to demonstrate that discretion was not exercised when treating individuals with NMSC, then they must reveal what treatments were selected, if any, when patients were stratified according to CCI. This may only come with publication of the overall data set. Linos and colleagues state that a significant proportion of NMSCs are asymptomatic and grow slowly and add that treatment benefits may not occur within the patient’s remaining life span. Are readers to believe that patients with CCI of 3 do not benefit from removal of their NMSC? Predictive models estimate that more than three-quarters of these patients will be alive for at least a decade after NMSC diagnosis. Although NMSCs may be asymptomatic, they frequently exhibit subclinical extension, resulting in larger tumors over time that are more challenging to treat. As NMSCs grow, they become more painful and invade surrounding structures such as nerves, vessels, and bone, and their subsequent eradication becomes significantly more involved than if they had been treated upon initial detection. A guiding principle of NMSC management is similar to that of melanoma—early detection and treatment. Patient outcomes such as morbidity and mortality are better with early detection and treatment of melanoma.21–24 Likewise, patient morbidity is significantly lower with early detection and appropriate treatment of NMSC.25 Thus, standard of care for NMSC should
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remain early treatment, regardless of the chosen modality (e.g., surgical excision vs curettage). It is precisely for this reason that the patients in the aforementioned clinical scenarios (CCI = 3) should be told they have “cancer” and not an “abnormal cluster of cells” as suggested in a recent blog highlighting the investigation in question.17 If the authors truly wish to support their notion that NMSCs are asymptomatic and slow growing, they must create a study arm in which NMSCs are prospectively followed without treatment (an ethical dilemma that no Institutional Review Board would be likely to approve). In the current study, only 3% of NMSCs went untreated, and no mention of patient outcomes in this subgroup is made. Linos and colleagues’ data demonstrate that, although their tumor “frequently bothered” fewer than one-quarter of all patients, their tumor was significantly more likely to bother individuals with LLE. Unfortunately, we currently lack predictive models that correlate symptomatology to tumor behavior. NMSCs that wreak the most havoc may be insidious for years after diagnosis. All too frequently, skin cancer specialists are encountered with elderly patients who present with devastating NMSCs that were simply “watched” for years. Treatment options for these patients sometimes require rhinectomy or orbital exenteration, woeful choices that could have been avoided with early treatment. Thus, a true argument for “discretionary” treatment of NMSC can only be made once similarly controlled groups are followed for 5–10 years, showing that untreated NMSCs have no worse morbidity than treated NMSCs. Clinical decision-making for NMSC must focus on patients and their wishes. Cutaneous oncologic literature has only recently begun investigating what it is that patients desire for treatment. A common theme that seems to be emerging is that NMSCs negatively affect patient quality of life (QOL) and psychosocial functioning.26–29 These findings are seen even in elderly adults.30 When a cohort of patients that was recently diagnosed with skin cancer was questioned about their wishes for skin cancer
treatment, the highest priority was placed on receiving a treatment that produces the highest cure rate.31 Although all treatment modalities for NMSC have varying amounts of success, surgical excision (Mohs surgery or traditional excision) has higher demonstrated cure rates than all other forms of treatment.32–35 Additionally, individuals with NMSC with fewer comorbidities have better quality of life with surgical treatment of their tumors.36 Perhaps it is this proven track record of producing the highest cure rate and better QOL that resulted in surgical excision being the treatment of choice in the current study. The authors’ conclusion that there was no variation in treatment choice according to patient prognosis must be further be scrutinized by examining the NMSC characteristics in their Table 1. Tumor characteristics that typically warrant surgical management (e.g., Mohs, excision) are larger size, location on the central face, and tumors that are symptomatic. In all three of these categories (size, site, symptoms), the LLE group had a statistically significantly larger amount. It is challenging to conclude that discretion was not exercised according to prognostic group when the LLE group inherently possessed numbers of indications that call for surgical treatment. The benefit of surgery in these scenarios is undeniable, and this finding indicates that the practitioners exercised clinical judgment when treating patient tumors. It would be helpful to determine whether “nonsurgical or destructive modalities” were more likely to be selected for NMSC of low-risk areas such as the trunk and extremities. The second contentious conclusion by Linos and colleagues relates to the concept of “complications.” Because death and life-threatening complications occur so infrequently in skin cancer surgery, other definable complications must be used. Traditionally, these include infection, bleeding, necrosis, and dehiscence. These variables are objective, easily measured, and often avoidable. Unfortunately, in this study, patients were asked to respond to the question, “In your opinion, were there any complications of your treatment during or after the treatment itself?” and then asked to grade the severity of
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the complication. It is not surprising that the “complication” rate approaches 20% for those with LLE because the authors allow anticipated effects such as numbness, itching, and discomfort to be tallied. No cutaneous procedure (surgical or destructive) comes without varying amounts of these subjective items. Informed consent with surgical and destructive treatments for NMSC necessitates that patients be aware that, although these undesirable events may occur, they are frequently transient and minor. The improper use of the word “complication” by the investigators creates unwarranted press fodder, particularly at a time when many are looking to criticize the benefits of office-based dermatologic surgery. When the term “complication” was responsibly qualified and quantified in a multicenter prospective cohort study of 1,792 skin cancer resections, no major complications were identified, and minor complications occurred in fewer than 3% of cases.6 As noted earlier, the most-recent multicenter study evaluating the safety of Mohs surgery concluded that fewer than 1% of patients experienced an adverse event.16 Most pertinent to this discussion is that, when a nonagenarian cohort of 214 patients was followed after skin cancer resection, fewer than 0.5% experienced a complication.37 These data highlight that the complications in the Linos and colleagues study are not complications. The authors would be advised to state what the true, objective complication rate is in all patients. Although it is worth noting how patients “feel” postoperatively, it is imperative that this be separated from what is measurable and avoidable. Identifying trends in skin cancer treatment is important in the changing healthcare climate. Epidemiologic studies have demonstrated not only a dramatic rise in the incidence of NMSC, but also a concomitant rise in the procedures performed to eradicate these tumors.38 This has resulted in NMSC becoming the fifth-most-expensive cancer to treat in the United States.39 This statistic, although frequently used to infer that NMSC treatment
may be overused, fails to highlight multiple important facts: NMSC accounts for 3.5 million cases of skin cancer each year—more than the next top four cancers combined (prostate 238,000, breast 234,000, lung 228,000, colorectal 142,000).40 Although the incidence of NMSC is staggering, the cost efficiency of treating NMSC in the United States is better than that of almost all other invasive forms of cancer. Treating a NMSC in the physician office setting provides care at $350 to $500 per episode,41 compared with $2,000 to $4,000 per episode for the next-four-most-common types of cancer (lung, prostate, colorectal, breast).39 Current treatment modalities for skin cancer are effective. NMSC survival rates approach 100% after treatment, whereas individuals with lung and colon cancer have survival rates of 17% and 65%, respectively, after treatment. The senior author of the article in question has published extensively on the topic of NMSC management and is to be highly commended for her diligence in attempting to address important and previously unanswered questions,36,42–48 but we find it highly unlikely that NMSC management in patients with LLE was the primary analytical question that was asked when the original database was generated. Subgroup analysis in other important scientific articles is often heavily scrutinized, and we believe that this article is analogous to such analysis. Furthermore, the omissions in the authors’ data set noted above leave many questions unanswered, most important of which is how the 492 missing CCI patients influence the results. This may heavily skew the data in a different direction. Is this why the LLE group was compared with the overall cohort rather than comparing the LLE group with the non-LLE group? Prior publications indicate that investigator research grants through the Department of Veterans Affairs and National Institutes of Health supported some of this author’s work. If this is the case, then it
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would be helpful to share the patient data set with other investigators so that many of these questions can be answered. A final point must be made concerning a commenter’s conclusion that “receipt of Mohs surgery is the most burdensome available treatment—taking much longer and with more potential complications that the other options.”2 Almost all credible published evidence vehemently counters this particular statement,6–8,16,49–51 and we believe that it is imperative that practitioners not familiar with the nuanced procedure be properly informed. Unfortunately, it is evident that patients and healthcare professionals may receive elements of misinformation when attempting to investigate the specifics of Mohs surgery.52 The benefits of Mohs surgery over other treatment modalities for NMSC are numerous.53 First, patient safety is paramount and is ensured (in almost all cases) through avoidance of general anesthesia and with the use of local anesthesia, particularly in patients with LLE.49,54–56 Second, 100% microscopic examination of tissue margins from resected tissue ensures the highest cure rate for NMSC and melanoma.32,33,57–60 Because of the elegant tissue preparation and microscopic mapping, precious tissue surrounding the tumor is spared.61 Through tissue conservation, smaller defects are encountered, which frequently translates to less-onerous reconstructions and better cosmetic outcomes. Often, performing Mohs surgery on sites such as the scalp, lower extremities, or concave portions of the face and ears permits a tumor to be resected more superficially than with traditional forms of surgical excision, which may allow patients to heal without any additional cutting or suturing. For patients who opt for repair of their Mohs defect, reconstruction almost always occurs on the same day of tumor resection. Although patients may spend hours of a day completing the numerous steps involved to clear a tumor and repair the wound, the great majority of the patients’ day is spent comfortably bandaged in a reception area as their tissue is processed in the
laboratory or as they wait to be repaired. As they wait, patients are able to fill their time as they see fit; some read or watch television, some choose to eat, and others sleep or complete work for their jobs. Patients value these qualities of the technique and do not view it as a burden.31 Finally, because of the aforementioned benefits, Mohs surgery is considered the cornerstone of cost-effective treatment for skin cancer.62–64 Uniform delivery of surgery to all individuals with NMSC is not the answer, but readers of Linos and colleagues should not be deterred from offering surgical treatment for NMSC in elderly adults and those with medical comorbidities. A dialogue must occur between practitioner and patient in which all treatment options are discussed. Patients must be made aware that skin cancer is more easily treated when detected early, that few predictive models exist regarding which cancers will become aggressive and destructive,65 and that outpatient dermatologic surgery is safe and comes with few complications. With these principles in mind, patients and family members can make informed and shared decisions with confidence.
References 1. Linos E, Parvataneni R, Stuart SE, Boscardin WJ, et al. Treatment of nonfatal conditions at the end of life: Nonmelanoma skin cancer. JAMA Intern Med 2013;173(11):1006–12. 2. Wenger NS. Skin cancer and shared decision making: comment on “treatment of nonfatal conditions at the end of life. JAMA Intern Med 2013;173:1012–10013. 3. Kwok AC, Semel ME, Lipsitz SR, Bader AM, et al. The intensity and variation of surgical care at the end of life: a retrospective cohort study. Lancet 2011;378:1408–13. 4. Chen JG, Fleischer AB Jr, Smith ED, Kancler C, et al. Cost of nonmelanoma skin cancer treatment in the United States. Dermatol Surg 2001;27:1035–8. 5. Starling J III, Thosani MK, Coldiron BM. Determining the safety of office-based surgery: what 10 years of Florida data and 6 years of Alabama data reveal. Dermatol Surg 2012;38:171–7. 6. Merritt BG, Lee NY, Brodland DG, Zitelli JA, et al. The safety of Mohs surgery: a prospective multicenter cohort study. J Am Acad Dermatol 2012;67:1302–9. 7. Kimyai-Asadi A, Goldberg LH, Peterson SR, Silapint S, et al. The incidence of major complications from Mohs micrographic
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surgery performed in office-based and hospital-based settings. J Am Acad Dermatol 2005;53:628–34.
25. Robinson JK, Fisher SG. Recurrent basal cell carcinoma after incomplete resection. Arch Dermatol 2000;136:1318–24.
8. Cook JL, Perone JB. A prospective evaluation of the incidence of complications associated with Mohs micrographic surgery. Arch Dermatol 2003;139:143–52.
26. Rhee JS, Matthews BA, Neuburg M, Logan BR, et al. Validation of a quality-of-life instrument for patients with nonmelanoma skin cancer. Arch Facial Plast Surg 2006;8:314–8.
9. Coleman WP, Hanke CW, Glogau RG. Does the specialty of the physician affect fatality rates in liposuction? A comparison of specialty specific data Dermatol Surg 2000;26:611–5.
27. Rhee JS, Matthews BA, Neuburg M, Logan BR, et al. The skin cancer index: clinical responsiveness and predictors of quality of life. The Laryngoscope 2007;117:399–405.
10. Neville JA, Housman TS, Letsinger JA, Fleischer AB Jr, et al. Increase in procedures performed at dermatology office visits from 1995 to 2001. Dermatol Surg 2005;31:160–2.
28. Rhee JS, Davis-Malesevich M, Logan BR, Neuburg M, et al. Behavior modification and risk perception in patients with nonmelanoma skin cancer. WMJ 2008;107:62–8.
11. Hancox JG, Venkat AP, Coldiron B, Feldman SR, et al. The safety of office-based surgery: review of recent literature from several disciplines. Arch Dermatol 2004;140:1379–82.
29. Burdon-Jones D, Thomas P, Baker R. Quality of life issues in nonmetastatic skin cancer. Br J Dermatol 2010;162:147–51.
12. Hancox JG, Venkat AP, Hill A, Graham GF, et al. Why are there differences in the perceived safety of office-based surgery? Dermatol Surg 2004;30:1377–9. 13. Venkat AP, Coldiron B, Balkrishnan R, Camacho F, et al. Lower adverse event and mortality rates in physician offices compared with ambulatory surgery centers: a reappraisal of Florida adverse event data. Dermatol Surg 2004;1:1444–51. 14. Otley CC, Fewkes JL, Frank W, Olbricht SM. Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs. Arch Dermatol 1996;132:161–6. 15. Balkrishnan R, Hill A, Feldman SR, Graham GF. Efficacy, safety, and cost of office-based surgery: a multidisciplinary perspective. Dermatol Surg 2003;29:1–6. 16. Alam M, Ibrahim O, Nodzenski M, Strasswimmer JM, et al. Adverse events associated with Mohs micrographic surgery: multicenter prospective cohort study of 20 821 cases at 23 centers. JAMA Dermatol 2013;149(12):1378–85. 17. Span P. Low-Risk Skin Cancers Often Treated Too Aggressively in Elderly, Study Finds. 2013. http://newoldage.blogs.nytimes.com/ 2013/05/06/low-risk-skin-cancers-often-treated-too-aggressivelyin-elderly-study-finds/?_php=true&_type=blogs&_r=0 18. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–83. 19. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47: 1245–51. 20. Moses S. Charlson Comorbidity Index. 2013.
30. Steinbauer J, Koller M, Kohl E, Karrer S, et al. Quality of life in health care of non-melanoma skin cancer—results of a pilot study. J Dtsch Dermatol Ges 2011;9:129–35. 31. Chuang GS, Leach BC, Wheless L, Lang PG, et al. Preoperative expectations and values of patients undergoing Mohs micrographic surgery. Dermatol Surg 2011;37:311–9. 32. Rowe DE, Carroll RJ, Day CL Jr. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. J Dermatol Surg Oncol 1989;15:315–28. 33. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip Implications for treatment modality selection. J Am Acad Dermatol 1992;26:976–90. 34. Leibovitch I, Huilgol SC, Selva D, Richards S, et al. Basal cell carcinoma treated with Mohs surgery in Australia II Outcome at 5-year follow-up. J Am Acad Dermatol 2005;53:452–7. 35. Mosterd K, Krekels GA, Nieman FH, Ostertag JU, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol 2008;9:1149–56. 36. Chren MM, Sahay AP, Bertenthal DS, Sen S, et al. Quality-oflife outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2007;127:1351–7. 37. Delaney A, Shimizu I, Goldberg LH, MacFarlane DF. Life expectancy after Mohs micrographic surgery in patients aged 90 years and older. J Am Acad Dermatol 2013;68:296–300.
21. Mitchell JK, Leslie KS. Melanoma death prevention: moving away from the sun. J Am Acad Dermatol 2013;68:e169–75.
38. Rogers HW, Weinstock MA, Harris AR, Hinckley MR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 2010;146:283–7.
22. Pennie ML, Soon SL, Risser JB, Veledar E, et al. Melanoma outcomes for Medicare patients: association of stage and survival with detection by a dermatologist vs a nondermatologist. Arch Dermatol 2007;143:488–94.
39. Housman TS, Feldman SR, Williford PM, Fleischer AB Jr, et al. Skin cancer is among the most costly of all cancers to treat for the Medicare population. J Am Acad Dermatol 2003;48:425–9.
23. Rossi CR, Vecchiato A, Bezze G, Mastrangelo G, et al. Early detection of melanoma: an educational campaign in Padova, Italy. Melanoma Res 2000;10:181–7. 24. MacKie RM, Hole D. Audit of public education campaign to encourage earlier detection of malignant melanoma. BMJ 1992;304:1012–5.
40. American Cancer Society. Skin Cancer Facts. http:// wwwcancerorg/Cancer/CancerCauses/SunandUVExposure/ skin-cancer-facts. 2012; Accessed July 13, 2012. 41. Mudigonda T, Pearce DJ, Yentzer BA, Williford P, et al. The economic impact of non-melanoma skin cancer: a review. J Natl Compr Canc Netw 2010;8:888–96.
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42. Chren MM, Sahay AP, Sands LP, Maddock L, et al. Variation in care for nonmelanoma skin cancer in a private practice and a veterans affairs clinic. Med Care 2004;42:1019–26. 43. Chen T, Bertenthal D, Sahay A, Sen S, et al. Predictors of skinrelated quality of life after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. Arch Dermatol 2007;143:1386–92. 44. Clark FL, Sahay A, Bertenthal D, Maddock L, et al. Variation in care for recurrent nonmelanoma skin cancer in a university-based practice and a veterans affairs clinic. Arch Dermatol 2008;144:1148–52. 45. Asgari MM, Bertenthal D, Sen S, Sahay A, et al. Patient satisfaction after treatment of nonmelanoma skin cancer. Dermatol Surg 2009;35:1041–9. 46. Asgari MM, Warton EM, Neugebauer R, Chren MM. Predictors of patient satisfaction with Mohs surgery: analysis of preoperative, intraoperative, and postoperative factors in a prospective cohort. Arch Dermatol 2011;147:1387–94. 47. Chren MM, Torres JS, Stuart SE, Bertenthal D, et al. Recurrence after treatment of nonmelanoma skin cancer: a prospective cohort study. Arch Dermatol 2011;147:540–6. 48. Chren MM, Linos E, Torres JS, Stuart SE, et al. Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2013;133:1188–96. 49. Alam M, Ricci D, Havey J, Rademaker A, et al. Safety of peak serum lidocaine concentration after Mohs micrographic surgery: a prospective cohort study. J Am Acad Dermatol 2010;63: 87–92. 50. Rogers HD, Desciak EB, Marcus RP, Wang S, et al. Prospective study of wound infections in Mohs micrographic surgery using clean surgical technique in the absence of prophylactic antibiotics. J Am Acad Dermatol 2010;63:842–51. 51. Larson MJ, Taylor RS. Monitoring vital signs during outpatient Mohs and post-Mohs reconstructive surgery performed under local anesthesia. Dermatol Surg 2004;30:777–83. 52. Miller CJ, Neuhaus IM, Sobanko JF, Veledar E, et al. Accuracy and completeness of patient information in organic World-Wide Web search for Mohs surgery: a prospective cross-sectional multirater study using consensus criteria. Dermatol Surg 2013;39:1654–61. 53. Brodland DG. Saving Face: The Skinny on Mohs Micrographic Surgery for Skin Cancer Skin Cancer Foundation 2012 [cited 2013 October 21]. Available from: http://www.skincancer.org/ skin-cancer-information/mohs-surgery/mohs-surgery-saving-face. 54. Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive
dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimer’s Dis 2010;22(Suppl 3):67–79. 55. Pedersen T. Complications and death following anaesthesia. A prospective study with special reference to the influence of patient-, anaesthesia-, and surgery-related risk factors. Dan Med Bull 1994;41:319–31. 56. Pedersen T, Eliasen K, Henriksen E. A prospective study of mortality associated with anaesthesia and surgery: risk indicators of mortality in hospital. Acta Anaesthesiol Scand 1990;34:176–82. 57. Foroozan M, Sei JF, Amini M, Beauchet A, et al. Efficacy of Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans: systematic review. Arch Dermatol 2012;148:1055–63. 58. Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 1989;15:424–31. 59. Rowe DE. Comparison of treatment modalities for basal cell carcinoma. Clin Dermatol 1995;13:617–20. 60. Etzkorn JR, Cherpelis BS, Glass LF. Mohs surgery for melanoma: rationale, advances and possibilities. Expert Rev Anticancer Ther 2011;11:1041–52. 61. Muller FM, Dawe RS, Moseley H, Fleming CJ. Randomized comparison of Mohs micrographic surgery and surgical excision for small nodular basal cell carcinoma: tissue-sparing outcome. Dermatol Surg 2009;35:1349–54. 62. Cook J, Zitelli JA. Mohs micrographic surgery: a cost analysis. J Am Acad Dermatol 1998;1:698–703. 63. Ravitskiy L, Brodland DG, Zitelli JA. Cost analysis: Mohs micrographic surgery. Dermatol Surg 2012;38:585–94. 64. Tierney EP, Hanke CW. Cost effectiveness of Mohs micrographic surgery: review of the literature. J Drugs Dermatol 2009;8:914–22. 65. Schmults CD, Karia PS, Carter JB, Han J, et al. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol 2013;149:541–7.
Address correspondence and reprint requests to: Joseph F. Sobanko, MD, Mohs & Reconstructive Surgery, Division of Dermatologic Surgery, Director of Dermatologic Surgery Education, Assistant Professor of Dermatology, Edwin & Fannie Gray Hall Center for Human Appearance, University of Pennsylvania, Philadelphia, Pennsylvania 19104, or e-mail: [email protected]