Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery: A Prospective, Multicenter Cohort Study

Key Points

Question  What are the characteristics of patients older than age 85 years with nonmelanoma skin cancer receiving Mohs surgery?

Findings  In this cohort study of 1181 patients older than age 85 years referred for Mohs surgery, those treated with Mohs surgery were more likely to have facial tumors and high functional status than those not treated with Mohs surgery. The 3 most frequently occurring reasons among surgeons for proceeding with Mohs surgery among patients aged older than 85 years were patient desire for a high cure rate, high functional status, and high-risk tumor type.

Meaning  These findings suggest that untreated skin cancer in older patients may be associated with functional loss, pain, and disfigurement.

Importance  It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs.

Objective  To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals.

Design, Setting, and Participants  This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019.

Exposures  Mohs surgery for nonmelanoma skin cancer.

Main Outcomes and Measures  Reason for treatment selection.

Results  Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]).

Conclusions and Relevance  This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Invasive keratinocyte skin cancers are typically treated surgically,^1,2 with patients receiving such treatment often being older than age 65 years. While surgery is safe even in individuals older than age 90 years,^3,4 concerns have been raised that some individuals may not need surgery given limited functional status and life expectancy.⁵ Overall, it has been suggested that decisions on skin cancer surgery in older patients should consider anatomic location of the tumor, tumor size, histologic characteristics, presence of comorbid conditions, symptomatology, associated levels of distress, and functional status.⁶ Fortunately, a study on patients older than age 75 years, and even older than age 85 years,⁷ found that patients who were more functional were more likely to receive surgery. Another study⁸ found that patients who were less functional were more likely to undergo other treatment types, even when they met appropriate use criteria for Mohs surgery. Among older patients, Mohs surgery is associated with an improvement in survival of almost 2 years vs similar cohorts who received other treatments.⁹ Risk assessments show that surgery has comparable adverse event rates in older and younger patients,^10,11 and older patients receiving surgery also report being highly satisfied.¹²

Evaluating whether Mohs surgery is necessary or appropriate for older patients requires complex value judgments that incorporate many factors, including patient preferences, net benefits of alternative treatments, resource availability and cost, and individual philosophical guideposts regarding the relative primacy of individual, community, and population health. More focused questions concern which individuals among older patients should receive Mohs surgery and why. Indeed, to our knowledge, there has not been a large, prospective, descriptive study to better characterize patients presenting for Mohs surgery for keratinocytic tumors.

The purpose of this study was to better characterize Mohs surgery in patients older than age 85 years. Specific aims were to investigate factors associated with the decision to undertake surgery and to characterize associated tumor-specific and demographic factors and indications for surgery as assessed by treating surgeons.

This prospective, multicenter cohort study was approved by the institutional review board (IRB) at Northwestern University and participating academic centers. It was deemed exempt from IRB review for all private sites by WCG IRB. Informed consent was obtained from all participants. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline was used.

Patients were enrolled at 22 academic and private practice skin cancer surgery centers in the US. Northwestern University was the data coordinating site.

Participants were consecutive patients older than age 85 years referred specifically for Mohs surgery, not for skin cancer management in general. Patients were referred primarily by dermatologists; infrequently by oculoplastic surgeons, otolaryngologists, or plastic surgeons; and not by primary care physicians.

Variables were patient age and sex, along with tumor type, anatomic location of tumor, preoperative clinically apparent tumor diameter, postoperative defect size, patient living environment, and reason for treatment selection (including functional status). Patient diagnoses were nonmelanoma skin cancer, primarily basal cell carcinoma (BCC), or squamous cell carcinoma (SCC). Treatment options were Mohs surgery or non-Mohs approaches, which included wide local excision, radical resection, electrodessication and curettage, photodynamic therapy, radiation, excision, topical chemotherapy, cryotherapy, systemic treatments (ie, chemotherapy, immunotherapy, and other), and surveillance.

Study personnel at designated institutions logged the number of patients referred for Mohs surgery and the number of completed surgeries. For patients older than age 85 years, additional data were collected on variables described previously.

Data were collected via a RedCap (Research Electronic Data Capture) online database (Dermbase II) in real time. Data acquisition occurred from October 28, 2014, to April 11, 2018, with an imbedded 6-month collection period for each center and with start dates staggered to minimize outcomes associated with seasonal variation.

Similar data fields were collected contemporaneously from consecutive patients younger than age 85 years presenting for Mohs surgery. This group was the reference group for all patients older than age 85 years regardless of treatment type. Additionally, patients older than age 85 years referred for Mohs surgery were stratified by those receiving and those not receiving Mohs surgery in the same age group.

The patient sample was not population based, but efforts were made to ensure that patient characteristics and tumor management were representative. Participating centers were geographically diverse, with 4 centers in the Northeast (18.1%), 6 in the South (27.2%), 9 in the Midwest (40.9%), and 3 in the West (13.6%). There were 12 centers in large central metro settings (54.5%), 5 in large fringe metro settings (akin to the suburbs; 22.7%), 4 in medium metro settings (18.1%), and 1 in a small metro setting (4.5%),¹³ and there were 13 centers among academic settings (59.0%) and 9 among private practice settings (40.9%). Surgeons varied in years of experience (mean [IQR], 18 [13-21] years) and resembled the national population.

The primary outcome of this study did not concern investigating whether differences existed between groups or an attempt to reject a null hypothesis. Therefore, a power calculation to determine a sufficient sample size was not needed.

The primary objective was to investigate reasons associated with patient assignment for Mohs surgery. To develop a list of possible reasons, one-on-one semistructured interviews were conducted with dermatologists expert in Mohs surgery to elicit a complete list of indications and reasons deemed sufficient to proceed with Mohs surgery or contribute to such a decision. Expertise was determined as evidenced by American College of Mohs Surgery membership and clinical practice focused on Mohs surgery for at least 5 years. Thematic saturation occurred after 12 interviews; 2 investigators trained in qualitative research methods transcribed interviews and extracted themes and reasons. When a surgeon decided to proceed with Mohs surgery, the physician was asked to check which of 15 distinct reasons led to or supported this decision. For functional status, respondents were referred to the Karnofsky Performance Status (KPS) scale and asked to specify when status was good to excellent, as determined by patients requiring minimum assistance with activities of daily living, defined as KPS values of 60% or greater.¹⁴ While informed consent was obtained before Mohs treatment and patient preference was considered a reason for Mohs surgery, comprehensive information regarding patient comments and preferences regarding treatment was not collected as part of this study.

Secondary objectives included characterizing demographic features and tumor characteristics of nonmelanoma skin cancer in patients older than age 85 years and comparing these patients with the reference group of those aged 85 years and younger. We computed the association of sex and age with living environment and anatomic tumor location. We also sought to identify patient and tumor factors associated with increased preoperative tumor size, postoperative defect size, and subclinical extension of cancer among patients older than age 85 years.

Data analysis was from November 2018 through January 2019. Statistical analyses were determined a priori. Descriptive information was obtained regarding reasons associated with Mohs treatment. Analyses apart from comparison of patients with the reference group of patients younger than age 85 years were performed after exclusion of patients presenting for surgery who did not receive it. Pearson χ² or Fisher exact tests were used, as appropriate, to compare categorical data between groups. For nonparametric continuous data, median values and IQRs were calculated.

Univariable linear regression examined the association between patient characteristics and preoperative clinically apparent tumor size (measured as the largest diameter, in centimeters), postoperative defect size, and subclinical extension (defined as the ratio of postoperative defect size to preoperative tumor size). Factors associated with tumor size, defect size, and subclinical spread in univariable analysis were used to construct multivariable linear regression models to investigate factors independently associated with each measure. We report β coefficients and 95% CIs for linear regressions. Statistical analyses were performed using SAS Studio statistical software version 3.71 (SAS Institute). P values were 2-sided, and P < .05 was considered statistically significant.

Missing data were detected by the data entry interface and in most cases generated an online error message that motivated correction by investigators at the participating site. Patients with partial data detected after completion of data collection were used in relevant analyses and omitted from analyses for which there were missing data.

Among 17 076 patients receiving treatment for nonmelanoma skin cancer at 22 sites, 1181 patients (6.9%) were older than age 85 years (724 [61.9%] men and 445 women [38.1%] among 1169 patients with sex data; 681 patients age >85 to age 88 years [57.9%] and 495 patients >89 years [42.1%] among 1176 patients with age data) were treated at 22 sites. Basal cell carcinomas occurred in 602 patients (51.0%), SCCs in 575 patients (48.7%), and other rare nonmelanoma skin cancers in 11 patients (0.9%). Characteristics of patients older than age 85 years and 3246 patients aged 85 years and younger (ie, the reference group) are shown in Table 1.

Among 1181 patients older than age 85 years referred for Mohs surgery, 1078 patients (91.3%) were treated with Mohs surgery and underwent further analysis (Table 2), while 103 individuals (8.7%) received alternate treatment. Of these patients, 24 individuals underwent electrodessication and curettage, 3 underwent photodynamic therapy, 62 underwent excision, 10 underwent topical chemotherapy, and 4 underwent cryotherapy. Patients treated with Mohs surgery were more likely to have tumors located on the face compared with those treated by other methods (738 patients [68.5%] vs 26 patients [25.2%]; P < .001). Conversely, patients receiving an alternate treatment were more likely to have lesions located on the trunk or extremities compared with those receiving Mohs surgery (45 patients [43.7%] vs 149 patients [13.8%]; P < .001). Patients receiving Mohs surgery were nearly 4-fold more likely to have high functional status vs those receiving alternative treatments (614 patients [57.0%] vs 16 patients [15.5%]; P < .001).

The frequency of reasons provided by surgeons for proceeding with Mohs surgery in patients older than age 85 years are in Table 3. Commonly reported reasons were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). The mean number of distinct reasons per patient was 3.2 reasons (95% CI, 3.1-3.3 reasons), and the median (IQR) was 3.0 (2.0-4.4) reasons. For almost all patients who received Mohs surgery (1076 individuals [99.8%]), Mohs treatment met criteria for appropriate use (ie, scores: 7-9). Among the remaining 2 patients, 1 individual was missing data, preventing calculation of appropriate use criteria score, and the other individual was of uncertain appropriateness (ie, scores: 4-6).

Squamous cell carcinomas were more common among patients older than age 85 years compared with the reference group of patients aged 85 years and younger (575 patients [48.7%] vs 1109 patients [34.2%]), whereas BCCs were more common in the reference group (2137 patients [65.8%] vs 602 patients [51.0%]; P < .001). Among BCCs, tumors with aggressive histologic subtypes (defined as infiltrative, morpheaform, micronodular, and metatypical or basosquamous subtypes) were more common among patients older than age 85 years compared with younger patients (223 patients [37.0%] vs 526 patients [22.6%]; P < .001). Similarly, among SCCs, macroscopically invasive tumors were more common among older patients (315 patients [54.7%] vs 361 patients [32.6%]; P < .001) (Table 1).

Sex was associated with anatomic tumor location. Among 724 men and 445 women older than age 85 years, men were more likely to have lesions on the scalp and neck (113 men [15.5% ]vs 39 women [8.7%]), and women were more likely to have lesions on the trunk or extremities (112 women [25.2%] vs 91 men [12.6%]) (P < .001) (Table 4).

Age and sex were associated with living environment. Among 681 patients older than age 85 to age 88 years and 495 patients aged 89 years and older, the younger patients were more likely to be living with a spouse or partner (348 patients [51.1%] vs 161 patients [32.5%]). Conversely, patients aged 89 years and older were more than 2-fold as likely as those older than age 85 to age 88 years to be living in a nursing home (49 patients [9.9%] vs 30 patients [4.4%]), with family members or friends other than a spouse or partner (58 patients [11.7%] vs 42 patients [6.2%]), or in assisted living facilities or at home with a home health nurse (30 patients [6.1%] vs 14 patients [2.1%]) (Table 4). Women older than age 85 years were 2-fold as likely to be living alone (216 women [48.5%] vs 171 men [23.6%]) or with family members or friends other than a spouse or partner (52 women [11.7%] vs 47 men [6.5%]) compared with men. Conversely, men were nearly 2-fold as likely to be living with a spouse or partner (413 men [57.0%] vs 95 women [21.3%]).

Factors associated with larger preoperative tumor size by univariable linear regression among patients older than age 85 years included tumor type (SCCs were more common than BCCs), living in a nursing home (vs with a spouse or partner), and tumor location on the scalp or neck or trunk or extremities compared with facial areas. Tumors located on the ears, eyes, lips, or nose were smaller than those on other facial areas (relative difference, −0.19 cm; 95% CI, −0.32 cm to −0.07 cm). Except for tumor type, all factors associated with preoperative tumor size were also associated with postoperative defect size (Table 5).

In multivariable analysis, living environment and anatomic location were independently associated with tumor size, defect size, and subclinical extension. Compared with living with a spouse or partner, living in a nursing home was associated with greater tumor size (relative difference, 0.41 cm; 95% CI, 0.21-0.61 cm) and defect size (relative difference, 0.57 cm; 95% CI, 0.21-0.94 cm). Living alone was also associated with a greater defect size vs living with a spouse or partner (relative difference, 0.23 cm; 95% CI, 0.03-0.43 cm). Compared with lesions on facial areas, those on the trunk or extremities were independently associated with greater tumor size (relative difference, 0.43 cm; 95% CI, 0.28-0.57 cm) and defect size (relative difference, 0.38 cm; 95% CI, 0.12-0.64 cm), as were those on the scalp or neck (relative difference in tumor size, 0.40 cm; 95% CI, 0.24-0.57 cm; relative difference in defect size, 0.42 cm; 95% CI, 0.13-0.71 cm). Conversely, lesions on the ears, eyes, lips, or nose were associated with smaller tumor size (relative difference, 0.19 cm; 95% CI, 0.07-0.32 cm) and defect size (relative difference, 0.45 cm; 95% CI, 0.23-0.67 cm) vs those on other facial areas.

Anatomic sites independently associated with less subclinical extension compared with facial areas included the hands and feet (relative difference, 0.31; 95% CI, 0.03 to 0.59), scalp and neck (relative difference, 0.23; 95% CI, 0.04 to 0.42), and trunk or extremities (relative difference, 0.18; 95% CI, 0 to 0.35). Compared with living with a spouse or partner, living with friends or family was associated with less subclinical extension (relative difference, 0.22; 95%CI, −0.43 to −0.01).

This multicenter prospective cohort study found that 6.9% of patients presenting for Mohs surgery were older than age 85 years. From among 15 possible reasons for selecting such surgery, surgeons reported a mean of 3.2 reasons per patient. Common reasons were patient desire for a high cure rate, good to excellent patient functional status, and high-risk tumor histology. Even among patients older than age 85 years referred for Mohs surgery, 9% of patients had tumors that were deemed inappropriate and received alternative treatment.

These findings suggest that patient functional status is associated with decisions on how cancers are treated, given that high-functioning status was among the most common reasons for surgery in patients older than age 85 years. This was second only to patient desire for high cure rate. These findings are consistent with prior work⁷ showing that most patients aged 75 years and older treated with Mohs surgery had high functional status.

Patient preference was cited as a reason for proceeding with Mohs surgery for 2% of patients. However, while patients were involved in the discussion regarding whether to proceed with Mohs surgery, a formal shared decision-making tool was not used, so this may be an underestimate. Had such a tool been used and had patients been counseled extensively about other options, it is possible that more individuals may have actively shown a preference for Mohs surgery or other options.

In patients older than age 85 years, SCCs were more common, as were macroscopically invasive SCCs and BCCs with aggressive histology. Moreover, SCCs among patients older than age 85 years tended to be larger than BCCs. Prior retrospective reviews^15,16 found that older men and women have proportionally more SCCs. This prevalence of SCCs, larger SCCs, and particularly aggressive BCCs in our cohort of patients older than age 85 years suggests that prompt Mohs surgery may be associated with minimized risk of metastasis and functional loss among a number of such patients.

Tumors in patients living in nursing homes had greater mean preoperative tumor diameter, and tumors in individuals living alone and in nursing homes had greater defect diameters than those among individuals living with a spouse or partner. Even among older patients, those older than age 88 years had relatively less social support. These findings suggest that advancing age and loss of social support may be associated with tumor neglect and growth. While individual circumstances vary, for patients who are high functioning and advancing in age or living in nursing homes, increased tumor surveillance may be associated with earlier tumor detection and mitigated growth. Tumor removal in this group may preserve quality of life that may otherwise diminish owing to tumor-associated symptoms (eg, bleeding or painful nonhealing lesions), functional loss, or social embarrassment leading to withdrawal. Ethicists agree that care should not be rationed based on patient age or infirmity and that every life has value.^17-20

In this study, subclinical extension was greatest on the face, followed by trunk or extremities, then scalp or neck and hands or feet. This is consistent with the expectation that Mohs surgery is most useful on the face, given that surgery is likely to effect cure while preserving function in the context of significant subclinical spread.

This study has several limitations, including that it was not population based. However, it included a large number of geographically diverse centers and is one of the largest prospective cohorts of older patients undergoing skin cancer surgery. Notably, this study could characterize only individuals presenting for Mohs surgery, and so the finding do not generalize to all patients with nonmelanoma skin cancer who have limited life expectancy. Specifically, there may have been a significant number of patients with limited life expectancy who were not deemed appropriate for Mohs surgery and thus were not included in this study given that they were not referred for Mohs treatment. Because reasons for surgery were assigned by the Mohs surgeon, there is potential for bias given that patients and Mohs surgeons may seek justification for the procedure given the expectations for Mohs surgery. Additionally, while patient preferences were considered, detailed information regarding patient-physician discussion pertaining to selection of treatment type and risks and benefits was not included. It is possible that some older patients may actively choose alternative treatments with goals that are different than the surgeon's goals, with patients, for instance, preferring wide excision over Mohs surgery based solely on the length of the procedure.

This cohort study found that older patients who presented for Mohs surgery often had multiple indications. Our findings suggest that Mohs surgery may be particularly appropriate in some older patients given that their tumors can be more aggressive and their social support may be more limited. For selected patients, surgical cure may be associated with lower burden of repeat or self-applied treatments. Future research may consider which nonsurgical treatments may be best when surgery is not appropriate.

Accepted for Publication: March 15, 2022.

Published Online: May 25, 2022. doi:10.1001/jamadermatol.2022.1733

Corresponding Author: Murad Alam, MD, Department of Dermatology, Feinberg School of Medicine, 676 N St Clair, Suite 1600, Chicago, IL 60611 (m-alam@northwestern.edu).

The Dermbase Research Group Authors: Simon Yoo, MD; Emily Poon, PhD; Vishnu Harikumar, MD; Alexandra Weil, BA; Sanjana Iyengar, MD; Matthew R. Schaeffer, MD.

Affiliations of The Dermbase Research Group Authors: Department of Dermatology, Feinberg School of Medicine, Chicago, Illinois (Yoo, Poon, Harikumar, Weil, Iyengar, Schaeffer); Department of Dermatology, West Virginia University, Morgantown (Iyengar); Department of Surgery, Wright State University, Boonshoft School of Medicine, Dayton, Ohio (Schaeffer).

Author Contributions: Dr Alam had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Schaeffer, Harikumar, Bolotin, Cohen, Farhang, Geronemus, Kimyai-Asadi, Kouba, Maher, Peterson, Yoo, Poon, Alam.

Acquisition, analysis, or interpretation of data: Maisel-Campbell, Weil, Iyengar, Schaeffer, Lin, Harikumar, Ibrahim, Kang, Anvery, Dirr, Christensen, Aylward, Bari, Bhatti, Cherpelis, Cohen, Condon, Farhang, Firoz, Garrett, Golda, Humphreys, Hurst, Jacobson, Jiang, Karia, Kimyai-Asadi, Kouba, Lahti, Council, Le, MacFarlane, Maher, Miller, Moioli, Morrow, Neckman, Pearson, Peterson, Poblete-Lopez, Prather, Ranario, Rubin, Schmults, Swanson, Urban, Xu, Poon, Alam.

Drafting of the manuscript: Maisel-Campbell, Schaeffer, Lin, Harikumar, Ibrahim, Kang, Aylward, Bhatti, Cohen, Farhang, Humphreys, Jacobson, Le, MacFarlane, Poblete-Lopez, Prather, Rubin, Alam.

Critical revision of the manuscript for important intellectual content: Weil, Iyengar, Ibrahim, Kang, Anvery, Dirr, Christensen, Bari, Bolotin, Cherpelis, Cohen, Condon, Firoz, Garrett, Geronemus, Golda, Hurst, Jiang, Karia, Kimyai-Asadi, Kouba, Lahti, Council, Maher, Miller, Moioli, Morrow, Neckman, Pearson, Peterson, Ranario, Schmults, Swanson, Urban, Xu, Yoo, Poon, Alam.

Statistical analysis: Maisel-Campbell, Schaeffer, Lin, Harikumar, Kang, Bhatti, Alam.

Administrative, technical, or material support: Weil, Iyengar, Schaeffer, Ibrahim, Kang, Anvery, Dirr, Christensen, Aylward, Bari, Bhatti, Cherpelis, Cohen, Condon, Firoz, Humphreys, Jiang, Karia, Kimyai-Asadi, Council, MacFarlane, Morrow, Peterson, Ranario, Rubin, Swanson, Xu, Poon, Alam.

Supervision: Cohen, Condon, Hurst, Kouba, Maher, Peterson, Yoo, Alam.

Conflict of Interest Disclosures: Dr Bolotin reported serving as principal investigator on a clinical trial sponsored by Replimune outside the submitted work. Dr Cohen reported serving as a clinical investigator, consultant, or speaker or trainer for Accure, Allergan, Almirall/Athenex, Avuta, Biofrontera Bioscience, Biopelle, Brickell Biotech, Croma, Elta, Endo Pharmaceuticals, Ferndale, Galderma, InMode, IntraDerm, Lutronic, Merz, Novan, PCA, Pulse Biosciences, Raziel, Recros Medica, Revance, Revision, Sciton, and Sente outside the submitted work. Dr Council reported receiving personal fees from Sanofi-Genzyme Regeneron, AbbVie, and Castle Biosciences outside the submitted work. Dr Schmults reported serving as the National Comprehensive Cancer Network nonmelanoma panel chair, on the American Society for Dermatologic Surgery board of directors, and as International Society for Dermatologic and Aesthetic Surgery secretary. No other disclosures were reported.

Funding/Support: This study was supported by departmental research funds from the Department of Dermatology at Northwestern University.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We would like to thank Rosemary King, PA-C (Saint Louis University), for her role with administrative and regulatory duties with this study. She was not compensated for this work.