FormalPara Key Summary Points

Skin cancer treatments often result in scars and physical side effects that, when located in highly visible areas such as the face and neck, can negatively impact patients’ quality of life.

Limited research has been conducted on the patient experience of those diagnosed with non-melanoma skin cancer, and specifically patients with cutaneous squamous cell carcinoma (CSCC).

This research identified unmet needs among patients with non-metastatic CSCC and provided a comprehensive understanding of the experience and treatment of these patients.

New patient-reported outcome (PRO) items were drafted to form the patient experience questionnaire for CSCC; these novel items will increase the conceptual coverage for future PRO assessment within trials intended to explore the clinical benefit of new treatments compared with surgery.

Introduction

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer after basal cell carcinoma (BCC), accounting for 20% of non-melanoma skin cancers (NMSC) [1]. CSCC occurs in individuals of all races and ethnicities, but most frequently in people with light skin susceptible to sunburn [2]. In most regions, the rates of CSCC incidence and death are higher among men than women, and the number of CSCC deaths peaks at a later age range in female patients (85–89 years) compared with male patients (80–84 years); the incidence of CSCC peaks at 70–74 years of age [3]. Immunosuppression is also associated with an increased risk of developing CSCC, and conditions such as solid organ transplant, chronic lymphocytic leukemia, chronic kidney disease, rheumatoid arthritis, and psoriasis are associated with worse outcomes [4]. In the past few decades, the number of CSCC diagnoses has increased by 50–300%, and incidence rates are predicted to rise with the aging population [5, 6].

Although CSCC has a relatively low mortality rate (1–3%), patients with regional lymph node involvement have a 10-year survival rate of < 20%; for those with metastases in the liver, brain, skin, lungs, and bone, the rate falls below 10% [7, 8]. Early and aggressive surgical excision is the primary method of treating localized CSCC that presents with high-risk features [8]. Around 5% of cases necessitate more complex therapies, such as systemic chemotherapy or immune checkpoint inhibitor therapy [9, 10].

The treatment of skin cancer, particularly of the face and neck, often results in scars and physical side effects that can negatively impact patients’ health-related quality of life (HRQoL) [11]; however, HRQoL in CSCC is not well understood. Prior HRQoL studies have been conducted in NMSC without stratifying by type, obscuring the experiences of people with CSCC [10]. Prompted by the dearth of published qualitative literature, this research explored the impact of disease and treatment on the experience of individuals with non-metastatic CSCC.

The aims of this research were: (1) to conduct patient-centered research to create a conceptual model of non-metastatic CSCC disease and treatment; (2) to determine the extent to which existing patient-reported outcome (PRO) instruments capture the disease and treatment experience of patients with non-metastatic CSCC; and (3) to develop a measurement strategy for future trials that may want to explore the clinical benefit of novel therapies in non-metastatic CSCC directly from patients’ perspectives.

Methods

This was a cross-sectional qualitative research study comprising desk research, interviews with dermatologists, and open-ended interviews with patients with a confirmed diagnosis of non-metastatic CSCC. Desk research included a literature review and reviews of patient blogs. Clinician interviews affirmed patient-reported concepts retrieved from the literature and blog review. These interviews confirmed and identified new concepts to inform the assessment of existing PRO instruments used in CSCC, and ultimately to develop the recommended measurement strategy. We have included the descriptions of appearance-related concerns on the basis of the sources we used, and whenever possible (i.e., if from expert or patient interviews) we used the patients’ exact words. This study is reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines (Supplementary Materials Table S1) [12].

Desk Research

The research team conducted two literature searches. The first used PubMed (Supplementary Materials Table S2) and patient blogs to assess the existing qualitative literature in the field of people living with CSCC, with particular attention to disease-related symptoms, impacts of symptoms on patients’ daily lives, and burden of treatment including treatment-emergent symptoms. The second search used PubMed (Supplementary Materials Table S3) and clinicaltrials.gov to identify PRO instruments that have been used to evaluate CSCC (for specific search strategies, see the Supplementary Materials).

Dermatologist Interviews

Input was sought from three expert dermatologists specializing in CSCC and Mohs surgery to guide study document development including the patient interview guide. Each had over a decade of experience in private practice and saw hundreds of patients with CSCC per year. Clinicians participated in interviews where they were asked about the signs and symptoms observed in patients with CSCC, as well as signs of improvements and deterioration over time and their observations of how patients experience Mohs surgery.

Patient Participants

The sample was comprised of adults in the USA who met the following pre-specified inclusion criteria: ≥ 18 years of age with a confirmed diagnosis of CSCC; a current lesion; Eastern Cooperative Oncology Group performance status of 0 or 1; willing and able to participate in one or two audio-recorded telephone interviews (lasting up to 1 h each); and the ability to speak, read, write, and understand English. After reviewing interim findings, inclusion criteria were updated to also include patients who had more invasive treatment of confirmed CSCC with a lesion on the head or neck and one or more Mohs surgeries (any location) in the past 6 months with at least two layers removed during surgery to clear margins. Ultimately, these additional criteria applied only to the final participant due to challenges finding eligible individuals. Participants were excluded from the study if they had any other cancer (except BCC) at the time of the study, or if their CSCC had metastasized to other parts of their body.

A healthcare research recruitment agency facilitated recruitment according to a screener that outlined the inclusion/exclusion criteria. Potentially eligible patients were identified via databases and clinician referrals, and were invited to take part via email. Of the patients screened for eligibility, 22 met all the inclusion criteria and none of the exclusion criteria. The adequacy of the sample size was assessed using saturation analysis (see below for further details).

Study documents, including the protocol, demographic and health information form, interview guide, screener, and informed consent forms received ethical approval from the Western Institutional Review Board (WIRB)-Copernicus Group Institutional Review Board (WCG IRB; ref number 20202867). All participants provided informed consent to participate and were compensated for their time in line with fair market value. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Patient Interview Content

Researchers conducted concept elicitation interviews to better understand the patient experience of CSCC. A semi-structured interview guide was developed as a foundation of the conversation. This was comprised of open-ended questions informed by our research objectives as well as insights from the clinician interviews. The guide also included structured prompts about symptoms and impacts experienced, the burden of treatment, and what aspects of CSCC were most bothersome. These prompts were only used if these topics did not emerge spontaneously in response to the open-ended questions. The qualitative interviews, which lasted approximately 1 h, were conducted remotely via audio calls using Microsoft Teams software, and were performed by experienced qualitative researchers who had been trained specifically for the study.

Qualitative Coding and Analysis

Verbatim transcripts were analyzed thematically [13] through detailed line-by-line inductive coding [14, 15] using ATLAS.ti software (Version 9, ATLAS.ti GmbH, Berlin, Germany). Independent parallel coding by two researchers was used to evaluate consistency using the first two interviews. The two lists of codes were compared for inconsistencies, and the coding was revised as needed. The tactic of coder triangulation was employed to reconcile any disparate data points and to reach convergence among coders [16]. Codes were organized on the basis of a clinical perspective to establish a clinically meaningful catalogue of the experiences of people with CSCC (e.g., lesion symptoms were differentiated from symptomatic adverse experiences of treatment).

Saturation Analysis

Saturation analysis was conducted to determine whether the sample size was sufficient. Saturation refers to data adequacy, or the point at which no new relevant information emerges from additional qualitative data [17,18,19]. This analysis was conducted by reporting new concepts that emerged in consecutive groups of five interviews, in line with the US Food and Drug Administration (FDA)’s patient-focused drug development guidance documents [20].

Development of the Preliminary Conceptual Model

A conceptual model is a visual representation of the concepts of interest identified by patients which are then organized according to proximal and distal concepts [13, 14, 21]. A conceptual model was constructed on the basis of all aspects of research by inductively categorizing concepts from patient interviews into higher-order overarching categories [13, 14, 21], organized as suggested by the FDA’s recent patient-focused drug development guidance [22]. In developing the conceptual model, researchers organized and ranked the patient-reported health concepts according to their relative proximity to the patient experience: lesion symptoms, for example, were given precedence over factors such as the experience of care. The conceptual model is for illustrative purposes only and does not imply any theoretical underpinnings.

Concept-to-Item Mapping

Items from existing PRO instruments collected during the second literature search were mapped to the concepts of interest relevant to patients with CSCC depicted in the conceptual model. The purpose of this systematic approach was to evaluate the extent to which existing PRO instruments measured what matters to patients and to identify which PRO instrument(s) are most relevant to people living with CSCC.

Item Generation and Development of a New PRO Instrument: The Patient Experience Questionnaire for CSCC

In cases where concepts from the model had no associated items in existing PRO instruments, additional items were developed. These items were mainly related to lesion symptoms, appearance, and treatment experience factors such as treatment bother and treatment satisfaction. A four-point Likert-type scale was used as response options (patients could also indicate that the item was non-applicable, if appropriate). The recall period used was in the past 7 days. The rationale for the choice of structure included, in part, alignment with the existing PRO instruments in the proposed measurement strategy, e.g., the FACE-Q® Skin Cancer questionnaire (used with permission according to the license agreement), part of a portfolio with several FDA-qualified tools [23].

Results

Desk Research

Qualitative Search

A search of PubMed identified 378 abstracts for screening. Ultimately, eight full-text articles were reviewed, and three were included in the analysis with associated concepts extracted. The major patient-reported concepts identified included lesion symptoms, overall appearance, appearance distress, cancer worry, sun behavior, negative treatment effects [appearance, negative treatment effects other (including symptomatic)], and experience of care.

Six blogs and advocacy group pages were also reviewed for concepts [selected on the basis of relevance and presence of direct patient quotes: cancer.net, Patients Like Me, Reddit support pages, Skin Cancer Foundation blog, Squamous Cell Carcinoma Foundation of SETX Facebook page, and Twitter posts (searched for groups or hashtags related to CSCC)]. These sources contained patient reports on lesion symptoms, overall appearance of the lesion, appearance-related adverse effects of treatment, other adverse effects of treatment not related to appearance, distress caused by appearance, worry about cancer overall, changes in behavior around sun exposure, and the experience of care. Detailed findings are available in the Supplementary Materials.

PRO Instruments Search

A total of 12 unique instruments were identified from PubMed and clinicaltrials.gov. Closer examination of the items and domains of the existing PRO instruments mapped to the conceptual model revealed that the most conceptually patient-relevant instruments were the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck questionnaire (consisting of 35 items), relevant items from the EORTC Item Library, and the FACE-Q® Skin Cancer questionnaire.

Sample Characteristics of Patients with CSCC Who Participated in the Interviews

A total of 22 patients with an average age of 48 years participated in interviews. The sample was predominately female (55%) and white (91%), with most participants receiving their diagnosis of CSCC more than 2 years prior to the time the study was conducted. Education levels ranged from high school graduate to post-graduate, and most were working full time (52%). Most of the participants reported receiving surgery (82%) as treatment for their CSCC. See Tables 1 and 2 for participant demographic and health information, respectively.

Table 1 Demographic characteristics of patients
Full size table
Table 2 Health information of patients
Full size table

Qualitative Results

Patients with CSCC reported lesion symptoms such as thickness, firmness, and discoloration, but did not report being particularly affected by these symptoms in terms of their ability to function. Some lesion symptoms, such as itchiness (severe at times), were bothersome to patients. Most patient concerns, however, were related to aesthetics: discoloration, thickness/bumpiness, crustiness, firmness, roughness, scaliness, flakiness, and peeling in the lesion area.

Most patients were generally satisfied with the most common form of surgical intervention, Mohs surgery. A subgroup of patients, however—including those with residual scarring, and those who experienced long wait times during the procedure—reported dissatisfaction and negative treatment effects. Patients reported:

What I dislike is that you’re left with scarring that will always remind you, hey, you had cancer. [I]t’ll be there like a tattoo all your days. (male, 50 years).

Mohs [surgery]... takes forever to heal... And it’s right where your bra strap goes over your shoulder… [A] lot of it is just nuisance and inconvenience. (female, 83 years).

Other patients reported additional adverse effects of treatment, such as anxiety:

[M]ore had to be removed tha[n] originally thought, but they don’t make promises during the Mohs surgeries. That’s the whole point of Mohs. This is just like we’re going to just take it until it’s done… It’s pretty nerve-wracking. (female, 49 years)

I was nervous. That’s what you could say about having it, because I wasn’t sure what it was going to be like. (female, 34 years)

Adverse effects also included bleeding, numbness, and pain/discomfort after the procedure; time for the treatment site to heal; and the need to follow up appropriately with wound care after surgery. Some patients reported scarring after surgery, which was a concern for those with a lesion in a visible location such as the face. Topical chemotherapy and photodynamic therapy did not provide the same resolution as lesion excision, and patients receiving chemotherapy reported itchiness and irritation.

Conceptual Model of the Patient Experience of Living with CSCC

The conceptual model was constructed by combining the results of the desk research and the findings of the qualitative interviews (Fig. 1). During interviews, patients reported that all or nearly all concepts under the “lesion symptoms,” “overall appearance,” “appearance distress,” “cancer worry,” “psychological impact,” “sun behavior,” and “negative treatment effects other” were important categories of the CSCC patient experience.

Fig. 1
figure 1

Conceptual model of patient experiences living with CSCC. Superscript 1 indicates the concept emerged from published qualitative literature and blogs; 2 from clinical websites (Mayo Clinic); 3 from clinical expert feedback; and 4 from participant interviews. CSCC cutaneous squamous cell carcinoma

Full size image

Saturation Analysis

All concepts emerged in the first three transcript groups, with most emerging in the first. Additional details of already existing adverse event concepts did emerge in the last group, but no new unique concepts were found. On the basis of these results, it was determined that conceptual saturation was reached with the first 22 interviews.

Assessment of Coverage for PRO Instruments and Development of a New PRO Instrument: The Patient Experience Questionnaire for CSCC

Conceptual coverage of the PRO instruments selected from desk research (EORTC and the FACE-Q® Skin Cancer modules) was assessed against the final conceptual model using targeted subdomains considered to be relevant to assess clinical benefit. The FACE-Q® modules were found to be more conceptually aligned with the targeted health concepts. Results from mapping of concepts to items for four of the most relevant six FACE-Q® Skin Cancer modules can be seen in Table 3. The relevant FACE-Q® Skin Cancer modules are FACE-Q® Satisfaction with Facial Appearance, FACE-Q® Appraisal of Scars, FACE-Q® Cancer Worry, and FACE-Q® Appearance-related Psychosocial Distress.

Table 3 Conceptual mapping of targeted health concepts to four selected modules of the FACE-Q® Skin Cancer or PEQ-CSCC
Full size table

For health concepts that did not have associated existing FACE-Q® Skin Cancer items, de novo items were developed that collectively formed the Patient Experience Questionnaire for CSCC (PEQ-CSCC). These items were developed using the same item stem and response options as items on the FACE-Q® Skin Cancer modules; items are in a draft stage and have not been debriefed with patients. Some potential concepts were eliminated or combined into a higher-level activity item owing to being too broad (e.g., inflammation), too specific, and thus not applicable to all (i.e., functional impacts, limitations doing specific activities, and limitations at work), or being signs but not symptoms (e.g., bruising, swelling, and peeling). The skin symptoms following treatment (e.g., numbness and soreness) were combined into one more general item, given that there were limited patient data to support separation of each into a single item.

Dermatologist Interviews

The three clinical expert dermatologists who were interviewed confirmed the concepts that emerged from patient interviews and desk research. In addition, these clinicians referred to concepts such as the psychological impact of CSCC, the impact of living with CSCC on sleep, and lesion-specific limitations such as the impact on socializing or using extremities affected by lesions.

Discussion

The conceptual model of the patient experience of non-metastatic CSCC reported in this research was derived from rich, detailed, patient-relevant empirical evidence. The model is, to our knowledge, the first to parse out the patient experience of non-metastatic CSCC. Most of the findings are nevertheless consistent with other qualitative work in aggregated patient populations, including the research leading to the FACE-Q® Skin Cancer questionnaire [24]. In that prior study, 15 interviews of patients with BCC, CSCC, or melanoma were conducted; the concepts reported included appearance-related concerns, psychological function, social function, adverse effects, and experience of care.

Although the four FACE-Q® Skin Cancer modules selected for evaluation provided the best conceptual coverage for evaluating patient experience in clinical research, some limitations were found. Some of the items are face-specific; depending on the context of use, wording may not be applicable (i.e., in populations with CSCC lesions on other parts of the body). Also, while one FACE-Q® Skin Cancer module assesses scarring post-surgery, it does not cover other appearance experiences or symptomatic adverse effects and functional limitations. These concepts emerged during the FACE-Q® development work, but no items were generated [24].

For concepts that did not appear to be covered by existing measures, researchers drafted new PRO items that collectively formed the PEQ-CSCC. These novel items, which are intended as a supplement to the FACE-Q® modules, will increase the conceptual coverage for future PRO assessment within trials intended to explore the clinical benefit of new treatments compared with surgery. Further research is warranted to confirm the content validity and psychometric properties of the PEQ-CSCC. Additionally, functional assessment via additional scales such as physical, role, emotional, cognitive, and social functioning scales of the EORTC Quality of Life Group Core Questionnaire or physical function scales from an existing item bank could be considered when planning for a comprehensive measurement strategy in clinical trials. It is important to remember that other factors beyond symptoms and direct impact of a specific treatment or disease contribute to the overall impact to patients. Typically, the type of surgery is determined by the type and location of skin cancer, but each patient will have a unique experience and different perception of impacts on their lives.

Our conceptual model also includes functional impacts, appearance distress, psychological impacts, negative treatment effects (appearance and other), and experience of care. The individual health experiences within these concepts, however, are slightly different in some cases (e.g., FACE-Q® development work reports a drooping eyelid after surgery). Notably, the FACE-Q® publication sample includes both patients with BCC and those with melanoma. The present study also uncovered some novel concepts absent from published work on FACE-Q®, including lesion symptoms, overall appearance concepts, impact on sleep, and sun behavior.

Finally, although this research provides unique and valuable contributions to the field of CSCC and measurement science, it does have some limitations. The sample population was predominantly female and white. While CSCC is more prevalent in lighter-skinned individuals [2], the appearance of lesions could be different for other races and ethnicities, or for non-female individuals. The size of the patient population could also be considered a limitation of the study. Future studies should include more diverse samples to ensure the results are inclusive of a broader population.

Conclusion

This research identified unmet needs among patients with non-metastatic CSCC, including a subgroup who reported negative treatment experiences, and provides a comprehensive understanding of the experience and treatment of these patients. A combination of FACE-Q® Skin Cancer modules, supplemented by the PEQ-CSCC and global items per broader category (covering multiple items e.g., “lesion symptoms overall”) to contextualize results and determine meaningful change, should be considered for evaluating the benefits of treatment in patients with unmet needs. These new items on the PEQ-CSCC should be cognitively debriefed with patients as well as studied further in terms of their modern and classical psychometric properties; this will inform a scoring algorithm and enable a description of results of future studies leveraging robust, patient-relevant, and meaningful endpoints.