A, Emotional functioning; B, daily activities; C, social functioning; D, physical function. laBCC indicates locally advanced BCC; mBCC, metastatic BCC.
BCC indicates basal cell carcinoma; BCCNS, BCC nevus syndrome.
Mathias SD, Chren M, Colwell HH, Yim YM, Reyes C, Chen DM, Fosko SW. Assessing Health-Related Quality of Life for Advanced Basal Cell Carcinoma and Basal Cell Carcinoma Nevus SyndromeDevelopment of the First Disease-Specific Patient-Reported Outcome Questionnaires. JAMA Dermatol. 2014;150(2):169-176. doi:10.1001/jamadermatol.2013.5870
Little is known about patients’ experiences of advanced basal cell carcinoma (aBCC) and basal cell carcinoma nevus syndrome (BCCNS), a rare genetic disorder that greatly increases the number of BCCs.
To develop a questionnaire to measure patient-reported outcomes (PROs) in these populations.
Design, Setting, and Participants
Concept elicitation interviews were conducted with patients with aBCC and BCCNS from 5 US clinical sites and the BCCNS Life Support Network and 4 physicians. The PRO questionnaires were drafted based on results from a literature review and findings from these interviews. Questionnaires were finalized after cognitive debriefing interviews were conducted with patients. Concept elicitation interviews were conducted with 30 patients (14 with aBCC, 16 with BCCNS) and 4 physicians (2 dermatologists, 1 Mohs surgeon, and 1 oncologist) in the United States. A subset of 10 of these patients (5 with aBCC, 5 with BCCNS) took part in cognitive debriefing interviews.
Main Outcomes and Measures
Development of 2 questionnaires to allow clinicians to assess the emotional, social, and physical impacts of the disease on patients with aBCC and BCCNS.
Most concept elicitation interview patients were male (63%) and white (93%); their mean age was 57 years. There were impacts on emotional, social, and physical functioning in both conditions. Patients were unable to do many activities and avoided other activities. Seventy-nine percent of patients with aBCC and all patients with BCCNS reported scarring. Physician interviews revealed similar findings. During cognitive debriefing interviews, the questionnaires were found to be relevant, clear, and comprehensive.
Conclusions and Relevance
Advanced BCC and BCCNS affect patients in unique and substantial ways. These PRO questionnaires were developed with patient and clinician input and measure the key areas that have an impact on patients with these conditions.
Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States, with approximately 2.8 million cases diagnosed in the United States each year.1 Basal cell carcinomas are typically localized in extent and successfully removed with surgery. A small subset of patients with BCC may develop locally advanced disease (laBCC), resulting in invasion into subcutaneous structures and extensive soft-tissue involvement, or metastatic BCC (mBCC). Collectively, laBCCs and mBCCs are termed advanced BCCs (aBCCs), which may involve critical structures in the head and neck region, frequently are recurrent, and can result in considerable patient morbidity with surgical or radiation therapy. These BCCs are more difficult to treat, particularly in patients who received inadequate early management.2 Metastatic BCC is rare, with an estimated incidence of less than 1%.3,4 Basal cell carcinoma nevus syndrome (BCCNS) is a rare genetic disorder, occurring in about 1 in 57 000 in the United States.5 Individuals typically develop BCC during adolescence or early adulthood and often develop multiple BCCs,6 a subset of which may also become advanced.
Despite the high prevalence of BCC and substantial research about its quality-of-life (QOL) effects,7 little is known about aBCC and BCCNS from the patient’s perspective. In addition to physical symptoms, there may be an impact on emotional and social functioning. Studies have shown an association between skin diseases involving visible lesions and depression or QOL,8,9 perhaps owing to embarrassment of disfigurement or scarring. However, the literature describing these issues for patients with aBCC and BCCNS is very limited. In a recent cross-sectional study of 32 patients with BCCNS, Skindex-29 scores revealed an impact on emotional and functional QOL. A subset of 18 individuals also completed the Center for Epidemiological Studies Depression Scale (CES-D). Fifty percent of those who completed the CES-D reported a score greater than 16, indicating a need for evaluation of clinical depression.10 Other questionnaires have recently been developed, including the 10-item Skin Cancer Quality of Life Impact Tool (SCQOLIT), to evaluate QOL in patients following treatment of non-mBCC skin cancer,11 and the 20-item Facial Skin Care Index (FSCI) to assess skin cancer concerns.12 However, the questionnaires were not designed to assess issues specific to patients with BCCNS or aBCC. A search of the published literature and ongoing or recently completed clinical trials (www.clinicaltrials.gov) revealed that no BCCNS- or aBCC-specific validated questionnaires are currently available.
This study sought to develop a patient-reported outcomes (PRO) questionnaire for patients with BCCNS and aBCC, using input from patients, clinical experts, and published literature.
The development of the newly developed PRO questionnaire occurred in 2 stages.
The first stage involved conducting concept elicitation interviews by telephone with individuals with BCCNS and aBCC to understand the impact on patients’ functioning and well-being. A semistructured interview guide containing 39 open-ended questions was developed based on the literature, clinical input, and information provided on the websites of BCCNS organizations (eg, Basal Cell Carcinoma Nevus Syndrome Life Support Network [www.gorlinsyndrome.org]13). During the approximately 60-minute interview, patients were asked about their disease; treatments received or surgical procedures undergone; symptoms and adverse effects; and impact of the disease and treatment on daily activities, emotional functioning, social functioning, and physical functioning. Telephone interviews were also conducted with 4 physicians (2 dermatologists, 1 oncologist, and 1 Mohs surgeon [S.W.F.]) who currently treat patients with BCCNS and/or aBCC. Physicians were asked to describe a typical patient with aBCC and/or BCCNS and the impact of their BCC and treatment on patients’ QOL.
All interviews were recorded, and transcripts were prepared, reviewed, and analyzed. Results are presented for the most commonly reported symptoms and emotions related to aBCC or BCCNS and the impact on functioning and daily activities.
Patients were recruited from 5 US clinical sites and the BCCNS Life Support Network.13 Patients were eligible if they were at least 18 years of age, determined to be a patient with aBCC or a patient with BCCNS with multiple BCCs and/or aBCC by a physician, a US resident with English fluency, were willing to sign an informed consent form, and were willing to take part in telephone interviews. A diagnosis of aBCC was at the discretion of the treating physician. Patients were excluded if cognitive or other impairment (visual, hearing) interfered with participating in a telephone interview. The study received institutional review board approval, and all participants provided written informed consent prior to participating in the study.
Patients with BCCNS identified concepts distinct from those with aBCC in the concept elicitation interviews. Therefore, 2 separate questionnaires for patients with aBCC and BCCNS were drafted. Cognitive debriefing interviews were conducted to evaluate the draft questionnaires with a convenience sample of patients who participated in the stage 1 interviews. These interviews sought to evaluate the content, clarity, and relevance of the newly developed questionnaires from the patient’s perspective. The PRO questionnaires were further revised based on cognitive debrief. An item-tracking matrix was developed to document revisions to the questionnaires with associated rationale.
Demographic characteristics (including age, sex, race/ethnicity, education level, employment, and marital status) were reported using counts and percentages. Responses from interview transcripts were entered into a spreadsheet and analyzed by response to each interview question. Transcripts were hand coded, and concepts were entered into a frequency grid, with the proportion of patients reporting each symptom or concept. Interviews continued until no new concepts were identified.
Thirty patients completed concept elicitation interviews: 16 diagnosed as having BCCNS and 14 as having aBCC (8 laBCC and 6 mBCC). Table 1 displays the demographic characteristics of the study participants. Most were male (63%) and white (93%), with a mean (SD) age of 56.9 (12.6) years. Most had at least some college education (67%), were married (60%), had an annual household income greater than $50 000 (40% [23% declined to answer]), and were retired, unemployed, or disabled (57%). Compared with patients with BCCNS, those with aBCC were older (51 years vs 64 years), and fewer were working outside the home (62% vs 21%). The mean time since their aBCC diagnosis was 15 years for patients with aBCC and 28 years for those with BCCNS. Patients with BCCNS reported a mean (SD) of 37.5 (62.8) BCCs (range, 2-250; median, 20) in the past 2 years vs 8.9 (10.1) (range, 0-30; median, 20) for those with aBCC. Eighty-one percent of patients with BCCNS had a relative living with BCCNS (data not shown).
When asked about their QOL (ie, “Overall, how does your condition affect your quality of life now?”), 64% of patients with aBCC and 40% of those with BCCNS reported that their condition was currently affecting their QOL; 34% of patients with aBCC and 60% of those with BCCNS responded with an answer such as “not at all” or “it doesn’t affect my quality of life at all.” Patients with aBCC who reported that their QOL was affected primarily described symptoms from their condition and/or treatment, while those with BCCNS reported that the disease had an impact on their social life, work or job opportunities, and ability to enjoy outdoor activities (data not shown).
Both patients with aBCC and those with BCCNS reported BCCs in a variety of locations, including the face, arms, legs, back, abdomen, and scalp. Most indicated that location did not have an impact on the type of symptoms experienced (patients with BCCNS, 57%; those with aBCC, 67% [80% and 50% of those with laBCC and mBCC, respectively]). Most patients with aBCC (79% [75% and 83% of those with laBCC and mBCC, respectively]) and 100% of those with BCCNS reported scarring as a result of treatment.
When asked about the most distressing aspect of their condition, patients with aBCC reported appearance, weight loss, feeling a loss of control, having a sense of doom, being upset that they did not seek treatment early enough, being concerned about future health problems, and being limited about what they could do and eat. Those with BCCNS reported distress about passing the condition to their children, their appearance (especially on the face), jaw cysts, the inconvenience of frequent physician visits and surgical procedures, the toll taken on their bodies, and fear of the future.
Symptoms, as reported by patients with aBCC and BCCNS, were common but differed between cohorts. As indicated in Table 2, the most commonly reported symptoms and adverse effects for patients with aBCC were hair loss (79%), loss of taste (79%), bleeding (57%), oozing or open wounds (50%), weight loss (50%), leg cramps (43%), changes in diet (36%), and itching (29%). Patients with BCCNS most frequently reported jaw cysts (81%), itching (69%), bleeding (44%), swelling (38%), palmar pits (31%), difficulty eating (25%), hair loss (25%), and leg cramps (25%). It should be noted that 40% of the patients interviewed were receiving vismodegib and, of those receiving vismodegib, 83% had aBCC.
Most patients reported impacts on emotional functioning, with a greater impact among patients with BCCNS (80%) vs those with laBCC (57%) or mBCC (67%) (data not shown). Table 3 displays the most commonly cited emotions. Patients with aBCC and BCCNS reported similar emotions, including feeling depressed or currently using antidepressants (36% and 56% of patients with aBCC and BCCNS, respectively), anxious (43% and 31% of patients with aBCC and BCCNS, respectively), worry about future surgical procedures (29% and 50% of patients with aBCC and BCCNS, respectively), and sadness (21% and 44% of patients with aBCC and BCCNS, respectively). In addition, 50% of patients with laBCC think about the possibility of BCC recurrence vs 73% of those with BCCNS. Two-thirds of patients with BCCNS (67%) reported fearing their condition will worsen vs 50% of those with laBCC and none of those with mBCC (Figure 1).
There is also an impact on the ability to engage in daily activities in both patients with aBCC and those with BCCNS (Figure 1). Most patients with aBCC (63% and 83% of those with laBCC and mBCC, respectively) reported difficulty in conducting daily activities owing to their condition, whereas only 27% of those with BCCNS indicated difficulty. Furthermore, 33% of patients with laBCC and 25% of those with mBCC reported changing aspects of their daily routine owing to their condition vs 50% of patients with BCCNS. Most patients were more cautious of engaging in behaviors that might worsen their condition, such as being in the sun or participating in outdoor activities.
In regard to overall impact on physical functioning, 27% of patients with BCCNS reported an impact compared with 60% of those with mBCC and 28% of those with laBCC (Figure 1). Many patients indicated that they often felt the desire to do things but could not because of their condition (those with BCCNS, 50%; those with mBCC, 67%; and those with laBCC, 50%). For example, some patients reported limiting physical activity after surgery to prevent stitches from “coming out,” whereas other patients are more careful when doing activities to avoid bumping their lesions. Approximately one-third of patients indicated an impact on their energy level, but most had enough energy to do the things they wanted to do (those with BCCNS, 75%; those with mBCC, 100%; and those with laBCC, 67%).
There was also an impact on social functioning in both populations (Figure 1). In response to an overall question about the impact of their condition on social functioning, 60% of patients with BCCNS reported an impact vs 25% of those with mBCC and 29% of those with laBCC. Many patients reported that their appearance made them feel less comfortable around others (53% of those with BCCNS; 33% of those with mBCC; and 57% of those with laBCC). Thirty-three percent of patients with laBCC and 15% of patients with BCCNS were afraid of not being accepted by others. None of those with mBCC reported having this fear.
Almost all patients (100% and 93% of those with BCCNS and aBCC, respectively) reported having support from family and friends. However, a moderate proportion of patients (38% and 21% of those with BCCNS and aBCC, respectively) indicated that their condition had an impact on their ability to be intimate with their partner or spouse. Fifty-seven percent of those with aBCC and 25% of those with BCCNS currently required assistance from family or friends. Most patients with BCCNS (81%) reported concern about the impact of their condition on their children or future children vs only 7% of those with aBCC (data not shown).
Interviews were conducted with 4 physicians (1 Mohs surgeon [S.W.F.], 2 dermatologists, 1 medical oncologist) experienced in the care of patients with aBCC and/or BCCNS. On average, participating physicians saw 14 patients with aBCC per month (range, 2-30 patients) and 3 patients with BCCNS per month (range, 1-7 patients). Individuals with aBCC typically received treatment for approximately 4 to 18 months, and those with BCCNS had been under their care for approximately 3 to 10 years. Patient age at the time of diagnosis varied (range, 20-70 years for both groups of patients).
All physicians indicated that location of BCCs had a significant impact on patients’ QOL, particularly if lesions were on the face. Physicians corroborated patients’ avoidance of activities (including social interactions), concerns around disfigurement, symptoms, and inconvenience of wound care and frequent treatment. Physicians also noted impacts on the patient’s work, feeling the need to change jobs or stop working when faced with multiple surgical procedures, scarring, and disfigurement. Physicians reported that patients most frequently complain about pain, bleeding, oozing, and odor from their lesions. They also indicated that patients with aBCC commonly worry about cancer in general and the possibility of additional tumors, whereas those with BCCNS express concern about the need for multiple surgical procedures and the possibility of subsequent disfigurement and feeling worn down.
Based on the findings from the literature search, patient concept elicitation interviews, and physician interviews, 2 draft PRO questionnaires were developed for patients with aBCC and BCCNS. These questionnaires were developed with the intent that they be used in conjunction with the Skindex-16, a validated health-related QOL, dermatologic-specific questionnaire used extensively in patients with skin cancer.14 The Skindex-16 addresses important aspects for patients with aBCC and BCCNS but not all the important concepts identified during the concept elicitation interviews. When developing the new measures for aBCC and BCCNS, steps were taken to ensure minimal overlap with the Skindex-16 content.
Ten patients who participated in concept elicitation interviews completed the draft questionnaires and participated in the cognitive debriefing interviews (5 patients with aBCC, 5 with BCCNS). Seven were female, 9 were white, and their mean age was 61 years of age (mean age, 71 years [range, 57-79 years] for those with aBCC; 51 years [range, 28-62 years] for those with BCCNS). Six patients were married, 6 had at least some college education, and most had an annual income of less than $75 000.
In general, respondents found the questionnaires to be clear, comprehensive, easy to complete, and suggested only minor revisions. Four items were added to both questionnaires to address feeling sad, adverse effects of treatment, impact on mobility, and sensitive or tender skin around lesions. Two symptom items were modified for clarity on the BCCNS questionnaire (ie, palmar pits or plantar pits, and pain or swelling from jaw cysts). A diagram of the concepts and sample questionnaire items within each corresponding concept is provided in Figure 2. The aBCC version contains 46 items, and the BCCNS version contains 62 items.
To our knowledge, we have developed the first aBCC- and BCCNS-specific questionnaires to measure the disease effects on patients’ QOL. These questionnaires were developed based on input from patients and physicians and findings from a literature review. Patients who responded to the draft questionnaires found them to be clear, comprehensive, and easy to complete.
These qualitative data highlight the considerable and varied ways in which aBCC and BCCNS affect patients. Patient concept elicitations interviews suggest that patients with aBCC and BCCNS may differ in regard to disease- and treatment-related experiences, largely owing to the heritable and life-long nature of BCCNS. Those with BCCNS know they will receive life-long treatment and procedures. Symptom profiles suggest that patients with BCCNS are similar to individuals with a chronic illness, whereas those with aBCC tend to have a profile more similar to that of individuals with acute or life-threatening disease.
Limitations exist despite the strengths of this study. Participants were recruited from clinical sites that participated previously in vismodegib clinical trials or the BCCNS Life Support Network. Our results likely reflect a treatment bias with vismodegib, as respondents reported a high proportion of adverse effects associated with vismodegib (eg, loss of taste, weight loss). In addition, our BCCNS sample may include participants who take a more active role in their treatment and management of their condition compared with an average patient with BCCNS. Treatment fatigue is common, resulting in some patients not actively seeking treatment or their physicians for periods of time. Different results may have been obtained from a more diverse group of patients, including those not actively seeking treatment or care from a physician. In addition, most of the concept elicitation interview participants was male, white, married, and had at least some college education. For the cognitive debriefing interviews, most were female, white, married, and with at least some college education.
In conclusion, findings from these interviews informed the development of 2 new PRO measures. The content, clarity, and relevance of the PRO measures were confirmed in cognitive debriefing interviews. Further research is ongoing to establish the psychometric properties of these newly developed questionnaires in populations of patients with aBCC and BCCNS.
Accepted for Publication: May 31, 2013.
Corresponding Author: Susan D. Mathias, MPH, Health Outcomes Solutions, PO Box 2343, Winter Park, FL 32790 (firstname.lastname@example.org).
Published Online: November 27, 2013. doi:10.1001/jamadermatol.2013.5870.
Author Contributions: Mss Mathias and Colwell had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition of data: Mathias, Colwell.
Analysis and interpretation of data: Mathias, Colwell, Yim, Chen, Fosko.
Drafting of the manuscript: Mathias, Colwell.
Critical revision of the manuscript for important intellectual content: Mathias, Chren, Yim, Reyes, Chen, Fosko.
Statistical analysis: Mathias, Chren, Colwell.
Obtained funding: Mathias, Yim, Reyes.
Administrative, technical, or material support: Mathias.
Study supervision: Mathias, Reyes, Chen.
Conflict of Interest Disclosures: Ms Mathias is an employee of Health Outcomes Solutions, which received funding from Genentech to undertake this research. Drs Chren and Fosko are paid consultants to Genentech, and Dr Fosko is also an investigator and speaker for Genentech. Ms Colwell is a consultant to Health Outcomes Solutions and was previously a consultant to Genentech (although not for this research study). Ms Yim and Drs Reyes and Chen are employees of Genentech and own stock and stock options.
Funding/Support: This study was funded by Genentech Inc.
Role of the Sponsors: The sponsors had no role in the conduct of the study; in the collection of data; or in the preparation of the manuscript. The sponsors had a role in the design of the study; in the analysis and interpretation of data; review of the manuscript.