A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma

Abstract

Introduction

Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients' perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients.

Methods

This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of superficial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying 'open-ended' questions and probing techniques intended to elicit patients' own description of their experiences with BCC. Telephone interviews lasted between 60 and 90 mins.

Results

Thirty-four interviews were conducted (G1: N = 13; G2: N = 21). The majority of patients were aged either 55-64 years (32%, N = 11) or 76+ years (32%, N = 11) and were primarily male (82%, N = 28); most (75%, N = 24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N = 16) or emotional well-being (71%, N = 15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N = 4; G2: 48%, N = 10).

Conclusions

Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective.

Funding

Eli Lilly and Company.

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A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma

Anna W. Steenrod . Emily Nash Smyth . Elizabeth N. Bush .

Anne Lynn S. Chang . Sarah T. Arron . Yolanda R. Helfrich .

Daniel D. Von Hoff . Leslie H. Brail . Karin S. Coyne

To view enhanced content go to www.dermtherapy-open.comReceived: May 28, 2015 / Published online: September 1, 2015 The Author(s) 2015. This article is published with open access at Springerlink.com

ABSTRACT

Introduction: Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients.

Methods: This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of supercial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying open-ended questions and probing techniques intended to elicit patients own description of their experiences with BCC. Telephone interviews lasted between 60 and 90 mins.

A. W. Steenrod and E. N. Smyth contributed equally to the manuscript.

Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s13555-015-0081-6

Web End =10.1007/s13555-015-0081-6 ) contains supplementary material, which is available to authorized users.

A. W. Steenrod K. S. Coyne

Evidera, Bethesda, MD, USA

E. N. Smyth (&) E. N. Bush L. H. Brail

Early Phase Medical, Oncology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USAe-mail: [email protected]

A. L. S. ChangStanford University, Stanford, CA, USA

S. T. ArronUniversity of California San Francisco, San Francisco, CA, USA

Y. R. HelfrichUniversity of Michigan, Ann Arbor, MI, USA

D. D. Von HoffTranslational Genomics Research Institute, HonorHealth, Phoenix and Scottsdale, Phoenix, AZ, USA

Present Address:L. H. BrailInnity Pharmaceuticals, Cambridge, MA, USA

184 Dermatol Ther (Heidelb) (2015) 5:183199

Results: Thirty-four interviews were conducted (G1: N = 13; G2: N = 21). The majority of patients were aged either 5564 years (32%, N = 11) or 76? years (32%, N = 11) and were primarily male (82%, N = 28); most (75%, N = 24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N = 16) or emotional well-being (71%, N = 15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N = 4; G2: 48%, N = 10). Conclusions: Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective.

Funding: Eli Lilly and Company.

Keywords: Basal cell carcinoma (BCC); Dermatology; Health-related quality of life (HRQL); Locally advanced; Metastatic; Non-advanced BCC; Non-melanoma skin cancer (NMSC); Qualitative; Symptomatology

INTRODUCTION

Basal cell carcinoma (BCC) is the most common cancer among fair-skinned individuals, with a wide range in age-standardized annual incidence by country from approximately 44745 per

100,000 for women and 541041 per 100,000 for men in Germany and Australia, respectively [13]. The incidence of non-melanoma skin cancer (NMSC), and specically BCC, is increasing worldwide. The incidence of NMSC procedures in the USA has almost doubled since 1994, and the total number of new cases in 2006 was estimated at 3.5 million per year, approximately 80% of which were BCC [4]. By 2030, it is anticipated that the number of cases presenting to dermatologists could increase by an estimated 50% [5]. Given that primary BCCs occur mostly on the areas of the body with the greatest sun exposure, approximately 70% occur on the head or face [6]. Less than 5% of all BCC cases become locally advanced or metastatic [7]. However, if untreated, these lesions can cause substantial local tissue destruction and disgurement [8]. Most BCC lesions can be removed through surgical measures; however, a small percentage of patients are unsuitable for surgery (because of the location or size of the lesion) or develop a more advanced stage of disease. These patients constitute a poorly dened (but small) percentage of overall BCC [9] and might have a greater disease impact [10].

Although several efforts have been made to determine the impact of NMSCs on the health-related quality of life (HRQL) of patients [1114], few studies have examined the specic impact of BCC. Patient-reported outcome (PRO) measures, such as the Skindex, Dermatology Life Quality Index (DLQI), and Short-form Health Survey-12 (SF-12), have been administered in studies of NMSC; however, these measures were designed to evaluate more general aspects of HRQL for non-cancer skin conditions [13, 15, 16]. Rhee et al. [17] developed and validated the Skin Cancer Index (SCI) to address the need for a disease-specic HRQL instrument in NMSC;

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METHODS

however, their study population was not BCC specic and only focused on patients who experienced skin cancer in the cervicofacial region. Burdon-Jones et al. [18] recognized and attempted to address the lack of knowledge related to non-metastatic skin cancer PRO measures by eliciting general opinions in writing from patients with malignant melanoma and NMSC, and concluded that a disease-specic measure for patients with both metastatic and non-metastatic disease was needed. Shingler et al. [10] conducted a health utility study that found that severe forms of BCC can represent a signicant psychological and cosmetic burden to patients, but these results were quantitative and did not give patients the opportunity to describe the burden in their own words. A recent study by Mathias et al. [19], undertaken to develop a BCC-specic PRO measure, found more substantial impacts related to daily activities and psychosocial effects in patients with more advanced stages of disease (locally advanced, metastatic BCC) compared with patients with basal cell nevus syndrome. However, consistent with Shingler et al. [10], Mathias et al. [19] did not provide an in-depth qualitative understanding of the patients perspectives.

Given that little has been done to fully understand experiences of BCC directly from patients, the primary objective of this study was to better characterize symptoms, the bothersomeness of symptoms, and the HRQL impact of BCC on the daily lives of patients across different stages of the disease. A secondary objective was to compare descriptively the experiences, symptoms, and HRQL impact of patients with non-advanced (including only supercial or nodular histology) BCC with those of patients with locally advanced or metastatic disease.

Study Design

This was a cross-sectional, qualitative study involving 34 telephone interviews with patients with BCC. Patients were recruited into two study groups depending on their disease stage using the American Joint Committee on Cancer (7th edn) staging criteria [20]: group 1 (G1) included patients with stage 1, non-advanced, BCC and group 2 (G2) included patients with locally advanced or metastatic BCC. Most patients (N = 32) were recruited from three clinical sites in the USA (two in California and one in Michigan). Two patients with BCC were recruited as part of a qualitative interview study (I4J-MC-HHBB [1.3]) that was being run in parallel to an ongoing, phase I, dose-escalation study (ClinicalTrials.gov #NCT01226485) for patients with advanced cancer (including a locally advanced or metastatic BCC group). All patient recruitment took place over the course of 10 months (March 2013December 2013). This parallel interview study was terminated early because of a lack of enrollment, but the data from the two interviews were included in the current analysis.

Institutional review board (IRB) approval was obtained before the start of the study and all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013, and Good Clinical Practices. All patients provided written informed consent before the start of the interview.

186 Dermatol Ther (Heidelb) (2015) 5:183199

Patient Recruitment

Patients were identied from patient databases or medical records at each clinical site or through participation in the ongoing clinical trial (ClinicalTrials.gov #NCT01226485). All patients were required to be aged 18 years or older, be able to participate in a telephone interview in English, and have the presence of measurable disease at the time of screening as dened by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). All patients had active disease that was either newly diagnosed or recurrent; G1 had been diagnosed with non-advanced BCC (including only supercial or nodular histology) and all patients in G2 had a diagnosis of BCC that was locally advanced or metastatic [20]. There were no restrictions based on location of the patients lesion(s) for participation in the study. Patients were not eligible if they had a clinically relevant medical or psychiatric condition that, in the opinion of the investigator or site coordinator, would interfere with the patients ability to complete the study.

Data Collection

All patients were screened over the telephone by site coordinators for inclusion in the study. Informed consent forms were mailed to patients and reviewed with scientic staff over the telephone before the start of the interview. Verbal and written informed consent was obtained from each patient. Patients participated in one telephone interview lasting between 60 and 90 min. All scientic staff was trained in the appropriate interview methods and conducted all interviews using a semistructured interview guide. A qualitative methodology was used by applying a combination of open-ended questions and

probing techniques intended to elicit patients own description of their experiences with BCC [21]. Interviews were conducted until saturation (or the point at which no new concepts emerged in the interview) was reached. Interview notes were systematically reviewed to enable continuous assessment of concepts over the course of the study and notes were tabulated to enable saturation to be assessed separately for each group of patients. Patients were asked to describe their cancer condition, current BCC-specic symptoms as well as HRQL impacts over the previous 7 days. Interviewers probed on each symptom mentioned, asking about intensity, severity, duration, bother, and any related limitations; understanding the impact of BCC-specic treatments was not within the scope of this research. Patients also provided demographic and BCC treatment information for descriptive purposes. A clinical form was completed for each patient by the site investigator (excluding patients who participated in the parallel interview study [I4J-MC-HHBB {1.3}]) outlining the length of time since BCC diagnosis, as well as prior and/or current therapies that patients were receiving for their BCC. All patients were reimbursed for their participation according to the fair market value based on the effort required for participation in the study.

Data Analysis

Descriptive summary statistics were used to summarize demographic and clinical information. A content analysis approach [22] was used to analyze the data (based on notes, transcripts, and audio recordings) from the telephone interviews. A coding dictionary based on the semistructured interview guide was developed before completion of data collection to ensure that interview transcripts

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were coded objectively and consistently. A qualitative analysis software program, ATLAS.ti (Muhr T. ATLAS.ti 5.0 edn. Berlin, Germany: ATLAS.ti Scientic Software Development GmbH; 2004), was used to organize and categorize systematically the text in the interview transcripts. Using a content analysis approach, the data were examined for general themes, as well as specic issues and concerns associated with BCC symptoms and impacts, with a focus on words or phrases that patients used to describe symptoms associated with the condition. All patient data for the analysis were deidentied before review by the sponsor of the study and co-authors.

RESULTS

Clinical and Demographic Characteristics

Thirty-four patient interviews were conducted (G1: N = 13; G2: N = 21). G1 comprised 11 patients with supercial subtype and two patients with nodular subtype BCC. G2 comprised 12 patients with metastatic BCC and nine patients with locally advanced BCC. Importantly, as data were collected, similar trends were observed in patient responses at an earlier time point for patients with non-advanced disease versus advanced disease; as a result, a smaller number of patients were recruited in G1.

The overall sample was mostly split between patients aged 5564 years (32%, N = 11) and those aged 76? years (32%, N = 11), and comprised primarily men (82%, n = 28). In G1, most patients (77%, N = 10) were older than 65 years, whereas, in G2, approximately half (48%, N = 10) were aged 5564 years (Table 1). Almost half of the patients (47%, N = 16) were married or living

with a partner and most patients (53%, N = 18) were retired or disabled. All patients had some form of health insurance, with more than half (59%, N = 20) using Medicare for coverage. Approximately half (56%, N = 19) reported having lived in a high-sun area when they were 1020 years old, although a greater proportion of patients in G1 (92%, N = 12) communicated that they were exposed to sun a lot during that time compared with patients in G2 (57%, N = 12). A high-sun area was not dened by geographical location, but rather was based on patient self-report and investigator discretion. Although more patients in G1 (69%, N = 9) reported having frequent sunburns when younger, fewer in G1 (38%, N = 5) reported having skin that burned easily compared with those in G2 (47%, N = 9).

Treatment History

Across both groups, most patients (84%, N = 27) had received pharmacologic therapy or had undergone procedures for BCC before the interview (Table 2). Surgical excision (53%, N = 17) and Mohs surgery (37%, N = 12) were the most common treatments received (by at least one-third of patients in each group). Almost half of the patients in G2 (47%, N = 9) had received vismodegib at some point previously. In terms of current treatment, most patients (75%, N = 24) were receiving some form of treatment, with almost equal amounts in both groups (G1: 77%, N = 10; G2: 74%, N = 14). Of those currently receiving treatment, vismodegib was the most common pharmacologic treatment at the time of their interview (19%, N = 6), which was recorded only for patients in G2, in line with the regulatory approved indication.

188 Dermatol Ther (Heidelb) (2015) 5:183199

Table 1 Patient demographic characteristics

Characteristics Total

(N 5 34)

Age (years), N (%)

3544 1 (3) 0 (0) 1 (5)

4554 3 (9) 2 (15) 1 (5)

5564 11 (32) 1 (8) 10 (48)

6575 8 (23) 5 (38) 3 (14) 76? 11 (32) 5 (38) 6 (29) Male gender, N (%) 28 (82) 10 (77) 18 (86) Marital status, N (%)

Single, never married 5 (15) 0 (0) 5 (24) Married and/or living with partner 16 (47) 6 (46) 10 (48)

Divorced 9 (26) 6 (46) 3 (14) Widowed 4 (12) 1 (8) 3 (14) Employment status, N (%)

Employed, part-time 2 (6) 0 (0) 2 (9)

Employed, full-time 9 (26) 4 (31) 5 (24) Retired 16 (47) 7 (54) 9 (43) Disabled 2 (6) 0 (0) 2 (9)

Unknown 5 (15) 2 (15) 3 (14) Highest level of education completed, N (%)

Less than high school 2 (6) 1 (8) 1 (5)

GED/high-school equivalent 4 (12) 1 (8) 3 (14) Some college 6 (18) 1 (8) 5 (24) Graduated 2-year college 3 (9) 2 (15) 1 (5)

Completed college degree 7 (21) 5 (38) 2 (9) Some postgraduate education 1 (3) 0 (0) 1 (5) Completed postgraduate degree 9 (26) 3 (23) 6 (29)

Vocational training 2 (6) 0 (0) 2 (9) Type of insurance, N (%)aMedicare 20 (59) 9 (69) 11 (52) Medicaid 2 (6) 1 (8) 4 (19)

Private health plan 14 (41) 5 (38) 9 (43)

Group 1: non-advanced (N 5 13)

Group 2: locally advanced and/or metastatic(N 5 21)

Dermatol Ther (Heidelb) (2015) 5:183199 189

Table 1 continuedCharacteristics Total

(N 5 34)

Group 2: locally advanced and/or metastatic(N 5 21)

Other insurance 9 (26) 6 (46)b 3 (14)c

Location of residence during ages 1020 years considered a high-sun area, N (%)

Group 1: non-advanced (N 5 13)

19 (56) 6 (46) 13 (62)

Exposed to sun a lot between age of 1020 yearsd, N (%) 24 (71) 12 (92) 12 (57) Frequent sunburns when youngerd, N (%) 17 (50) 9 (69) 8 (38) Skin burns easilyd,e, N (%) 14 (44) 5 (38) 9 (47)

ERP extended reporting period, GED general education development, MCE medicaid coverage expansion, VA veterans health association

a Not mutually exclusive

b Other (N) includes VA System (N = 5) and ERP Supplement (N = 1)

c Other (N) includes VA System (N = 1), VA Health Insurance (N = 1), and MCE. On the county system (N = 1)

d Based on self-reported experience with sun exposure; responses included yes responses only

e Does not include patients recruited from the NCT01226485 study (N = 2); denominator of N = 32 was used for this question

Diagnosis and Perceived Severity of Disease

A greater proportion of patients in G2 (57%, N = 12) considered their condition to be more severe compared with patients in G1 (23%, N = 3). When characterizing the severity of their cancer, all patients mentioned the impact on their lifestyle and life expectancy, as well as the quantity and frequency of lesions appearing. In addition, patients in G2 discussed the emotional distress of the cancer when describing their disease severity, whereas patients in G1 did not. Three patients (G1: 8%, N = 1; G2: 9%, N = 2) had difculty deciding on the severity of their cancer because of the discord between the severity reported by their doctor compared with their own understanding of their health and skin cancer condition. The way in which patients were rst found to have BCC was almost identical in both groups, with the exception of

three patients in G2, who reported waiting longer to seek treatment, thus resulting in more severe disease and greater impact, such as disgurement. Most patients (G1: 61%, N = 8; G2: 67%, N = 14) sought medical care because of physical symptoms, such as lesions or bumps, which resulted in a diagnosis. Other patients (G1: 31%, N = 4; G2: 33%, N = 7) reported going to the doctor for unrelated reasons, such as a routine physical examination, when they were rst found to have BCC.

Patients in both groups mentioned experiencing growths in similar locations on their bodies, such as their face, arms, chest, scalp, or head. Patients in G2 also reported lesions on their back and neck. Most patients (76%, N = 16) in G2 described their lesions as visibly apparent to others, compared with 23% (N = 3) in G1. Patients in G2 also tended to experience more lesions at a given time and had a longer history of experiencing lesions.

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Table 2 Patient clinical characteristics

Characteristics Total

(N 5 32)

Years receiving care at practicea

Mean (SD) 4.9 (6.8) 4.4 (5.3) 5.3 (7.8) Range 0.130.0 0.120.0 0.130.0 Years since BCC diagnosisMean (SD) 8.0 (12.0) 2.9 (6.8) 11.4 (13.6) Range 0.043.0 0.024.0 0.043.0 Previous treatment procedures, medication, or chemotherapy for BCC, N (%)bYes 27 (84) 10 (77) 17 (89) Electrodessication and curettage 2 (6) 2 (15) 0 (0) Surgical excision 17 (53) 8 (61) 9 (47) Chemotherapy 1 (3) 0 (0) 1 (5) Radiation 3 (9) 0 (0) 3 (16) Vismodegib 9 (28) 0 (0) 9 (47) Pain medications 1 (3) 0 (0) 1 (5) Topical (5-FU, imiquimod) 1 (3) 1 (8) 0 (0) Mohs surgery 12 (37) 5 (38) 7 (37) Otherc 2 (6) 0 (0) 2 (10) None 5 (16) 3 (23) 2 (10) Current treatment procedures, medication, or chemotherapy for BCC, N (%)bYes 24 (75) 10 (77) 14 (74) Electrodessication and curettage 1 (3) 1 (8) 0 (0) Surgical excision 5 (16) 3 (23) 2 (10) Radiation 1 (3) 0 (0) 1 (5) Vismodegib 6 (19) 0 (0) 6 (32) Pain medications 3 (9) 1 (8) 2 (10) Topical (5-FU, imiquimod) 2 (6) 2 (15) 0 (0) Mohs surgery 4 (12) 2 (15) 2 (10) Otherd,e 7 (22) 3 (23)d 4 (21)e None 8 (25) 3 (23) 5 (26)

Table does not include two patients from NCT01226485 clinical trial 5-FU uorouracil, PDT photodynamic therapy, SD standard deviation

a Dened as the number of years a patients has been receiving care at the recruiting medical site

b Responses are not mutually exclusive

c Other (N = 2) includes clinical trial (N = 1) and ne-needle aspiration (N = 1)

d Other (N = 3) includes pending Mohs surgery in January 2014 (N = 1), shave biopsy (N = 1), and sunscreen (N = 1)

e Other (N = 4) includes arsenic trioxide (N = 2), following with oncologist (N = 1), and oculoplastics, ear, nose, throat (ENT) bone excision, and probably postoperative radiation (N = 1)

Group 1: non-advanced (N 5 13)

Group 2: locally advanced and/or metastatic (N 5 19)

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Table 3 Patient-reported symptoms and impacts

Overall, N (%) Total(N 5 34)

Group 1: non-advanced (N 5 13)

Group 2: locally advanced and/or metastatic(N 5 21)

Symptomsa

Red lesions or open sores 14 (41) 7 (54) 7 (33) Cancer-related stress 14 (41) 5 (38) 9 (43)

Itching localized to the lesion 13 (38) 6 (46) 7 (33) Pain related to cancer 10 (29) 0 (0) 10 (48) Bleeding lesions 9 (26) 4 (31) 5 (24)

Problems sleeping 8 (23) 2 (15) 6 (29) Lack of energy 3 (9) 0 (0) 3 (14) Hair loss 3 (9) 1 (8) 2 (9)

Depression 2 (6) 0 (0) 2 (9) Muscle cramps 2 (6) 0 (0) 2 (9) Dizziness 1 (3) 0 (0) 1 (5)

Skin discoloration 1 (3) 1 (8) 0 (0) ImpactsDaily activities 22 (65) 6 (46) 16 (76) Emotional well-being 21 (62) 6 (46) 15 (71)

Social and/or leisure activities 15 (44) 4 (31) 11 (52) Cosmetic and functional 14 (41) 4 (31) 10 (48) Work and/or studies 9 (26) 2 (15) 7 (33)

Personal relations 9 (26) 2 (15) 7 (33) Sexual activities 5 (16) 1 (8) 4 (19)

a Includes only patients who reported symptoms related specically to their cancer; all treatment-related symptoms were excluded from the analysis and reporting

Symptoms

The symptoms reported by patients were common across groups, and almost all patients in G1 (85%, N = 11) and G2 (95%, N = 20) were experiencing at least one symptom related to their BCC at the time of the current study

(Table 3). Patients in G2 reported a larger number of different symptoms and a greater frequency of specic symptoms compared with patients in G1. The most frequently reported symptoms overall were red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). Among

192 Dermatol Ther (Heidelb) (2015) 5:183199

patients in G2, red lesions or open sores that failed to heal were more commonly reported by patients with locally advanced disease (38%, N = 5/13), whereas cancer-related stress was largely reported by patients with metastatic disease (75%, N = 6/8). Other commonly reported symptoms included itching localized to the lesion site (38%, n = 13), bleeding lesions (26%, N = 9), and problems sleeping (23%, N = 8). Pain related to cancer was frequently reported by G2 patients only (48%, N = 10).

At the conclusion of the interview, patients were asked which symptoms they considered the most bothersome. Most patients in G2 (95%, N = 20) identied one or more symptoms as most bothersome compared with 69% (N = 9) of patients in G1. Patients in G1 (N = 4) had greater difculty in identifying a bothersome symptom because they either had only one symptom or did not consider their symptoms to be bothersome. Across both groups, of the 29 patients who reported at least one bothersome symptom, the most commonly reported were cancer-related stress (24%, N = 7), itching localized to the lesion (24%, N = 7), and open sores that failed to heal (14%, N = 4) (Table 4).

Impact

All patients were asked whether their BCC had impacted their daily activities, emotional well-being, social or leisure activities, work or studies, personal relations, or sexual activities over the previous 7 days. Table 3 summarizes this impact quantitatively.

Daily ActivitiesA greater proportion of patients (76%, N = 16) in G2 reported experiencing some impact on daily activities compared with those in G1 (46%, N = 6). When asked how their cancer

had affected their daily activities, 31% (N = 4) of patients in G1 and 57% (N = 12) of patients in G2 mentioned having to limit activities, such as exercise, strenuous activities, such as lifting heavy objects, or outdoor activities, to avoid sun exposure.

Patients in G2 (19%, N = 4) also mentioned experiencing fatigue, which limited their ability to complete chores or other household activities, whereas patients in G1 (31%, N = 4) mentioned needing to be more cautious when doing activities as a result of surgeries or symptoms. One patient in G1 and four patients in G2 mentioned having to change their schedules and daily activities because of doctors appointments or when recovering from surgeries.

Emotional Well-BeingCompared with G1, a greater proportion of patients in G2 reported being emotionally impacted by the disease (G1: 46%, N = 6; G2: 71%, N = 15). Approximately half of the patients in G2 (48%, N = 10) reported feeling self-conscious or embarrassed about their appearance because of the scarring or appearance of the lesions. Nineteen percent (N = 4) and 23% (N = 3) of patients in G2 and G1, respectively, mentioned being bothered by others staring at their lesions or scars.

Patients also reported being worried, stressed, or concerned about their health and the cancer (G1: 8% N = 1; G2: 24% N = 5) and being frustrated or upset with the reoccurrence of the cancer (G1: 15% N = 2; G2: 19%, N = 4). A few patients in G1 (15%, N = 2) and G2 (14%, N = 3) mentioned being depressed because of their cancer.

Social ImpactAbout half of the G2 patients (52%, N = 11) and one-third of G1 patients (31%, N = 4) reported an impact on their social or leisure activities

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Table 4 Patient quotes regarding most bothersome symptoms

Most bothersome symptoms

N (%)a Group 1: non-advanced Group 2: locally advanced and/or metastatic

Yeah, an open bleeding wound, well, it would bleed sometimes and sometimes not. And, uh, it starts off a little slow, but just keeps growing bigger and bigger and eating more and more, uh, outward esh. (Pt ID: 002-103)

So it starts small and gets bigger and you said an open bleeding wound? (Interviewer)

Uh-huh [yes], the doctors call it moth eating, when the wound nally opens up, so thats how they describe it. (Pt ID: 002-103)

Cancer-related stress

Open sores that failed to heal

4 (14) Yeah, it wouldnt heal over, like aif youif Id jabbed it with a knife or something it would heal, but, uh, this was just a little sore that, uh, whenever I washed my face if it had any kind of a scab on there, it would come off and wouldnt heal. (Pt ID: 002-201)

7 (24) Immediately around the time of being biopsied and nding the results, Id say that for me is pretty severe. Now Im just sort of waiting to get through the process, and then its going to be very stressful the day of the surgery and the day after for sure. And then, it just sort of levels off again. (Pt ID: 003-201)

Id say stress related to the cancer is the most bothersome and biggest issuetheres an unknown component whether its going to heal or not and whether its going to leave physical scars or not. (Pt ID: 001-208)

Um, when I get upset because of the stress, uh, itit becomesyou know, yes, Im bothered by it. On, uh, a daily thing when Im not doing anything great or anything and I dont get worked up, uh, I think the, uh, medication works ne and I can control it. But its just when things start going backwards, which they do quite a lot, um, then it starts becoming an issue. (Pt ID: 002-103)

Probablyat this point, probably the stress of the unknown because I know the itching will go away and the redness will go away. (Pt ID: 002-111)

Itching localized to the lesion

7 (24) Um, I have itching or, um, a discomfort, its like, uh, a sore or a mosquito bite or something thats there, you know. (Pt ID: 001-204)

Ituh, its bothersome, you know, its like any itch you have, you want to scratch it. You know you shouldnt in this case and that thats whats, uh, the bother really. (Pt ID: 002-201)

Itching anduh, itching and burning because that causeswhen I rub that it causes it to bleed. You know, even if you rub on the side of it or something, uh, then the scab comes off. So the itching is what triggers it. (Pt ID: 003-105)

The symptoms listed were described by patients as their most bothersome symptoms during the interview discussion Pt ID patient identier

a A denominator of 29 was used to calculate the percentages; this is based on the total number of patients who reported at least one most bothersome symptom

194 Dermatol Ther (Heidelb) (2015) 5:183199

Table 5 Patient quotes regarding impacts and change in behavior

Impact on HRQL

Group 1: non-advanced Group 2: locally advanced and/or metastatic

Daily activities Well, like, right now because this is still a bit of an open wound, you know, I have to be careful I, you know, dont pump my heart rate up too high at the gym and things like that. (Pt ID: 003-201)

Well, Im stuck inside, like I said. II mean, I can jump in the car and go to the store and stuff. But Im limited to doing normal things of going outside, maybe going to ato a baseball game, or going to the park and just goingfor a walk. I cant do any of those things. (Pt ID: 001-018)

Emotional well-being

Uh, Im tired of having my body cut. I mean, you could say its at times mildly depressing. (Pt ID: 001-205)

You know, I know its, now that I know what it is, I want to get rid of it. But, I know other people see it on my skin and wonder what that is. I dont know. (Pt ID: 001-103)

Well, I dontI dont like it when people stare at me. Um, it makes me a little bit uneasy; especially the little children. That bothers me. (Pt ID: 001-016)

Social impact Yeah, Im not as motivated, you know, I justIm tired, uh, when youre not sleeping you dont have that energy to goto go out there andand do those things [hiking with dog or going snowshoeing with friends]. II try to push myself too when I have a good days, but theres been a lot more bad days.(Pt ID: 002-202)

I dont know if its leisure, but its basically all the yard work. Back when they were open sores it would stop [me from] meeting peopletalking to people and basically staying in. (Pt ID: 002-108)

Cosmetic and functional impact

Well, I wear the hat and the wig because after all these surgeries II have no hair, its all scar tissue and [sigh] I think my mind has shut down. (Pt ID: 002-202)

Uh, a great, gaping wound on my face and no ears, I mean as soon as you look at me you can tell something is denitely wrong with this guy. (Pt ID: 002-103)

Change in behavior

Um, the only change in lifestyle that Ive done, as a result of the cancers, is I am much more aware of being in the sun without some sort of protection. (Pt ID: 001-205)

I might go outside and that sun hits this open wound on the side of my face its just like putting it in a fry pan. I always wear a great big broad brim hat and stuff, um, when I go outside. (Pt ID: 002-103)

HRQL health-related quality of life, Pt ID patient identier

because of their cancer. The most common reasons included having to reduce outdoor activities (G1: 15%, N = 2; G2: 24%, N = 5), such as hiking, gardening, and going to watch

baseball games, as well as spending less time with friends and family (G1: 23%, N = 3; G2: 24%, N = 5) because of their appearance. Patients also reported that the time spent

Dermatol Ther (Heidelb) (2015) 5:183199 195

receiving medical treatment (including transportation) limited their activities.

Cosmetic and Functional ImpactCosmetic and functional impacts resulting from cancerous lesions or cancer-related surgeries were described by patients in both groups. Almost half of G2 patients (48%, N = 10) described functional and cosmetic impacts, such as visible scarring (9%, N = 2), malformation of the skin because of the cancerous lesions (24%, N = 5), or having part or all of a body part (i.e., ears or eyes) removed because of surgery (19%, N = 4). One-third of patients in G1 (31%, N = 4) were concerned with the need for repeat surgeries and the potential for scarring, especially in places on the body that were highly visible to others. Patients across both groups also communicated a feeling of fear, stress, and embarrassment associated with the cosmetic and functional impacts.

Changes in Behavior

Changes in behavior were reported almost equally across both groups (G1: 100%, N = 13; G2: 91%, N = 10/11); limitations on sun exposure were reported most commonly (G1: 92%, N = 12; G2: 82%, N = 9/11). Almost half of the patients in both groups (G1: 38%, N = 5; G2: 48%, N = 10) reported wearing additional clothing to protect themselves from the sun and wearing a hat when going outside (G1: 31%, N = 4; G2: 24%, N = 5). Patients also reported reducing or limiting sun exposure by wearing sunscreen or seeking shaded areas.

A few patients in both groups (G1: 15%, N = 2; G2: 36%, N = 4/11) mentioned having to alter their clothing as a result of their surgeries

by wearing more loosely tted clothing or wearing clothing to hide a symptom of the cancer, such as a red lesions or open sores.

Select patient quotations characterizing BCC-specic impacts and changes in behavior affecting HRQL are documented in Table 5.

DISCUSSION

Although several efforts have been made to determine the impact of NMSC on HRQL, few studies have examined the specic impact of BCC. This study was conducted to generate descriptive information specic to BCC. Importantly, patients with either non-advanced or locally advanced or metastatic BCC experienced symptoms and impacts from their disease that affected their HRQL. Although there were some commonalities between the two groups, there were some key differences that are important to highlight.

Overall, a greater proportion of patients with locally advanced or metastatic disease deemed their condition to be severe compared with patients with non-advanced disease. Patients in G2 were more likely to describe frequent and bothersome symptoms and expressed experiencing a greater HRQL impact across six of the seven categories evaluated compared with patients in G1. Pain related to cancer was reported by approximately half of G2 patients, whereas it was not reported by any patient in G1. Similar to Mathias et al. [19], the current study found that impacts on emotional well-being and daily activities were common and more frequently reported in patients with more advanced disease. Consistent with Shingler et al. [10], the current study also found that BCC imposes a signicant psychological and cosmetic burden on patients, as demonstrated by approximately 50%

196 Dermatol Ther (Heidelb) (2015) 5:183199

of G2 experiencing visible scarring, malformation of the skin, or loss of a body part.

Although more subtle, disease stages that are non-advanced can impose bothersome sequelae and negative impacts on patients HRQL. Despite the relatively small sample size of G1, approximately half of patients reported the disease as having a negative impact on their emotional well-being and daily activities. In addition, anxiety related to potential or existing scarring, as well as tumor recurrence, was communicated by one-third of the sample.

These ndings, similar to those of Burdon-Jones et al. [18], suggest that, although the burden can be less when compared with those with more advanced disease, it is important to assess HRQL in all patients with BCC. In our study, the domains or themes that emerged as the most important to assess a patients HRQL across both groups included cosmetic and functional impacts, emotional well-being, and changes in behavior and daily activities to avoid sun exposure. These domains, particularly the fear of scaring and disgurement and the importance of avoiding excess sun, also corresponded to the important themes identied by Burdon-Jones et al. [18], providing additional evidence to support the impact of these domains in the BCC patient population.

In addition, the ndings from this study also suggest that, although is it important to evaluate the HRQL in both groups of patients, different aspects of the HRQL domains are more relevant based on the stage of the disease. For example, the impact on daily activities is an important domain to measure in both populations. Most patients with non-advanced disease experienced cutaneous surface-level symptoms, such as red spots or localized itching, which tended to affect daily activities that pertained to limiting sun exposure or modifying clothing selections. However, in

patients with more advanced disease, the daily activities affected were changes in lifestyle, such as the inability to clean the house or reductions in exercise. Based on these differences, PROs in the local disease population should focus on these initial behavioral changes in terms of daily impact, whereas patients with advanced disease should be more broadly assessed, given the number of activities limited by their condition.

In addition, because of the number of patient comments regarding healthcare utilization and time burden, it would be useful to examine the healthcare resource utilization in both patient groups to gain a better understanding of the economic and time burden associated with BCC. Many patients were currently undergoing treatment at the time of the interviews, and both patient groups mentioned the burden associated with treatment, such as scheduling appointments, the cost of the procedures, and reduced or loss of productivity while recovering from surgery.

Although the study was intended to characterize the patient population, several limitations should be considered when interpreting these results. Patients for both groups were difcult to recruit. Given the accessibility and effectiveness of surgery in those with non-advanced disease, many eligible patients did not have current baseline disease and were ineligible for the study. This requirement of measurable disease, however, reduced the possibility of recall bias which could otherwise have been considered as an additional limitation to these results. Likewise, the recruitment of patients with locally advanced and metastatic disease was difcult because of the rarity of this advanced disease stage. This resulted in a long recruitment period for a limited number of interviews and a sample of patients from only two states (California and

Dermatol Ther (Heidelb) (2015) 5:183199 197

CONCLUSION

Michigan), which decreases the generalizability of these results. In addition, because of the difculty in recruiting patients, all qualitative interviews were conducted over the telephone and not in person. Although not ideal for facilitating communication between patients and interviewers, conducting qualitative interviews by telephone did enable increased patient participation, especially for those patients who had progressive disease or were older and being cared for by another. Other limitations that should be taken into consideration include the relatively few female participants, as well as other variables not controlled for in this study that could inform patients impressions of their disease (i.e., education regarding BCC, experience of family or friends with BCC, or impact of treatments).

A strength of the study was the use of qualitative methodology, which enabled exploration of concepts with patients in a not well-understood population. In addition, conducting interviews with patients at varying stages of disease provided an understanding of HRQL along the progression of disease, which has not been previously done.

This study provides insight into a patient population that has not previously been well dened in the literature. Future studies with a broader scope might be interested in highlighting similarities and/or differences between BCC and other types of skin malignancy in terms of disease symptoms and HRQL impact. Although the information gained from this study lls a gap in the scientic literature and supports the development of measurements to evaluate new therapies, studies in larger numbers of patients with BCC (including a greater proportion of women) are warranted to rene the concepts most relevant to this population of patients.

Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Providing this patient perspective on important symptoms and HRQL impact helps to more broadly characterize the inuence of different disease stages of BCC on the daily life of patients and provides a foundation for additional renement of concepts most relevant to them.

ACKNOWLEDGMENTS

Sponsorship and article processing charges for this study were funded by Eli Lilly and Company, Indianapolis, IN, USA. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given nal approval to the version to be published. The authors thank Katherine Kim, Kelly McQuarrie, and Katie Devine, all of whom were employees of Evidera, for their contribution during the early stages of this research and their assistance with conducting the patient interviews. Editorial assistance was provided by Kawthar Nakayima of Evidera and funded by Eli Lilly. The authors gratefully acknowledge all patients who participated in this research.

Conict of interest. This research study was supported by Eli Lilly and Company, Indianapolis, IN, USA. Anna Steenrod and Karin Coyne are employees of Evidera and were paid scientic consultants to Eli Lilly and Company in connection with the Qualitative

198 Dermatol Ther (Heidelb) (2015) 5:183199

Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma study. Anne Lynn S. Chang is afliated with Stanford University, Stanford, CA, USA. Sarah T. Arron is afliated with University of California, San Francisco, CA, USA. Yolanda R. Helfrich is afliated with University of Michigan, Ann Arbor, MI, USA. Daniel D. Von Hoff is afliated with the Translational Genomics Research Institute and HonorHealth in Phoenix and Scottsdale, AZ, USA. Dr Chang received a grant from Eli Lilly and Company for the conduct of Protocol I4 J-MC-HHBB (Phase 1 Dose-Escalation Study of LY2940680 in Patients with Advanced Cancer). Dr Von Hoff received a grant from Eli Lilly and Company for the conduct of Protocol I4 J-MC-HHBB (Phase 1 Dose-Escalation Study of LY2940680 in Patients with Advanced Cancer) and Protocol Addendum I4 J-MC-HHBB (1.3) (Exploratory Study of Basal Cell Carcinoma Patient Experience). He has also received an honorarium from Eli Lilly and Company for delivery of an educational presentation on perspectives in drug development. Elizabeth Bush and Emily Nash Smyth are employees and shareholders of Eli Lilly and Company, Indianapolis, IN, USA. Leslie H. Brail was an employee and shareholder of Eli Lilly and Company at the time this study was conducted; he is now an employee of Innity Pharmaceuticals. All of the authors had full access to data and were involved in critical review and editing of the manuscript. The manuscript underwent scientic quality and legal review by Eli Lilly and Company before submission. All authors provided nal approval of the manuscript before submission.

Compliance with ethics guidelines. All procedures followed were in accordance with the ethical standards of the responsible

committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

Open Access. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/

Web End =http://creativecommons.org/licenses/ http://creativecommons.org/licenses/by-nc/4.0/

Web End =by-nc/4.0/ ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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