Date Published: October 1, 2017
Publisher: JKL International LLC
Author(s): Simone Garcovich, Giuseppe Colloca, Pietro Sollena, Bellieni Andrea, Lodovico Balducci, William C. Cho, Roberto Bernabei, Ketty Peris.
Skin cancer is a worldwide, emerging clinical need in the elderly white population, with a steady increase in incidence rates, morbidity and related medical costs. Skin cancer is a heterogeneous group of cancers comprising cutaneous melanoma and non-melanoma skin cancers (NMSC), which predominantly affect elderly patients, aged older than 65 years. Melanoma has distinct clinical presentations in the elderly patient and represents a challenging question in terms of clinical management. NMSC includes the basal cell carcinoma and cutaneous squamous cell carcinoma and presents a wide disease spectrum in the elderly population, ranging from low-risk to high-risk tumours, advanced and inoperable disease. Treatment decisions for NMSC are preferentially based on tumour characteristics, patient’s chronological age and physician’s preferences and operational settings. Several treatment options are available for NMSC, from surgery to non-invasive/medical therapies, but patient-based factors, such as geriatric comorbidities and patient’s life expectancy, do not frequently modulate treatment goals. In melanoma, age-related variations in clinical management are significant and may frequently lead to under-treatment, limiting access to advanced surgical and medical treatments. Clinical decision-making in the care of elderly skin cancer patient should ideally implement a geriatric assessment, prioritizing patient-based factors and efficiently differentiating fit from frail cancer patients. Current clinical practice guidelines for NMSC and melanoma only partially address geriatric aspects of cancer care, such as frailty, limited life-expectancy, geriatric comorbidities and treatment compliance. We review the recent evidence on the scope and problem of skin cancer in the elderly population as well as age-related variations in its clinical management, highlighting the potential role of a geriatric approach in optimizing dermato-oncological care.
We conducted a literature search in the relevant databases (PUBMED, EMBASE, Web of Science), employing the following keywords and their respective combinations: “elderly”, “older patient”, “skin cancer”, “non-melanoma skin cancer”, “basal cell carcinoma”, “cutaneous squamous cell carcinoma”, “cutaneous melanoma”, “frailty”, “oncogeriatric assessment”, “oncogeriatric intervention”, “quality of life”, “life expectancy”, “treatment of skin cancer”. Relevant published studies and reports from 1996 onwards were included. We reviewed the relevant papers and current clinical practice guidelines related to skin cancer (BCC, cSCC and CM) for age-related variations in clinical management and for oncogeriatric aspects of care. We described key aspects of epidemiology, clinical presentation and management for the main skin cancers, BCC, cSCC and CM, in the elderly patient, focusing on potential key-areas for an oncogeriatric intervention.
The National institute on aging has characterized the aging of our society as a “silver tsunami for which we are unprepared” . Currently, more than 50% of all cancer are diagnosed in patients 65 years and older and this proportion is expected to increase up to 70% by 2030 . Thus, with the progressive aging of the population, geriatric care has become a major issue for health authorities.
BCC can be managed with a wide spectrum of treatment options, employing both surgical and non-surgical (medical or physical) modalities. Treatment of BCC is aimed at complete removal of the primary tumour, while minimizing the risk of local spread and maximally preserving the contiguous tissues, thus giving the best functional and cosmetic outcome. The choice of the most appropriate treatment is correlated to the characteristics of the primary lesion as well as to patient’s specific factors . The various treatment modalities are summarized in Figure 1 and include surgery (curettage, conventional excision, Mohs micrographic surgery), radiotherapy and physical treatments (electrodessication and curettage, laser ablation, cryosurgery, photodynamic therapy), medical topical (imiquimod, 5-fluorouracil) and systemic therapies (vismodegib). The current standard of care for BCC is represented by surgery, ranging from standard elliptical excision to complex, micrographic-controlled surgical interventions (Mohs technique) with histological excision-margin control, depending on tumour characteristics, tumour location and regional involvement . BCC area classified in low-risk and high-risk tumours based on risk of recurrence, number of lesions (single or multiple), size, location and clinico-pathological phenotype. High-risk BCC are already relapsed tumours or at risk of recurrence after local treatment/excision, frequently involving the “mask-area” of the face and peri-orificial skin areas. Clinico-pathological phenotypes of BCC also guide treatment decisions, as superficial BCC in low-risk skin areas are easily managed with topical therapies (imiquimod, 5-fluorouracil) and other destructive modalities (cryosurgery, electrodessication with curettage). Nodular, sclerodermiform and infiltrating lesions in high-risk areas should always be treated with surgery, with larger lesions requiring complex defect repairs (skin grafts, flaps and multi-stage surgery), eventually in combination with adjuvant radiation therapy .
Cutaneous squamous cell carcinoma (cSCC) is a typical tumour of elderly individuals, resulting from the malignant transformation of keratinocytes of the epidermis and its appendages. It is a typical tumour of advanced age (mean age of 70 years at diagnosis), with more than 80% of cases occurring in old patients. Invasive cSCC represents roughly 20% of NMSC, developing de-novo on chronic sun-exposed skin or from precursor lesions, the in-situ, intraepidermal cSCC (Bowen’s disease) or actinic keratosis (AK). cSCC arises typically on chronic sun-exposed skin areas, involving the head and neck area as well as the dorsal aspects of the upper limb area in almost 90% of cases . Epidemiological data on cSCC incidence, mortality and disease burden is limited and fragmented, as these tumours are excluded from national cancer registries. Moreover, there is a potential overlap of in case-definitions of cSCC with the broad category of head-and neck cancers. In most epidemiological studies on cSCC, tumours of lip vermillion area and ano-genital cSCC area excluded from analysis. Studies from different western-industrialized nations have reported a dramatic increase (50-200%) in incidence rates of cSCC during the past three decades, reflecting an increase of cumulative UV-exposure and and an aging population . In the United States (2012), estimated cSCC cases in the white population ranged from 186,157 to 419,843, with nodal disease involving between 5604 and 12,572 persons, depending on latitude and UV index . Age-standardized incidence rates for cSCC present a marked geographic variability, ranging from 30 per 100.000 persons/year in Germany to 1332 per 100.000 persons/year in Australia . Disease-specific mortality of non-genital cSCC is generally considered to be low (1.5-2.1% estimated risk) and declining in several western countries, but there are several areas of uncertainty related to misclassification of disease coding. Recent estimates report between 3932 to 8791 cSCC-related deaths in the United States, with regional figures in central and southern states exceeding mortality from melanoma, renal cell and oro-pharyngeal carcinoma . Incidence of cSCC increases dramatically with age, as cumulative, chronic (occupational or recreational) sun exposure is the main risk factor for development for this keratinocytic tumours . Other predisposing factors include exposure to ionizing radiation, toxic chemicals (arsenic acid, polycyclic hydrocarbons) and very long-lasting cutaneous inflammation associated with chronic wounds, ulcers, radiodermitis, old burn and scars . Immune suppression, as observed in Organ transplant recipients (OTRs) and during treatment of haematogical conditions, is another strong risk factors for cSCC, influencing also disease progression and course .
Current standard of care for cSCC is described in details in the European (EADO/EDF) and American (NCNN) guidelines, with treatment options summarized in Figure 2 [63,64]. As in BCC, complete surgical excision with histopathological control of excision margins represent the gold-standard of treatment of primary invasive cSCC. Standard surgical excision and Mohs micrographic surgery and its variants determine optimal disease control in more than 90% of cases, while preserving normal tissue function and adequate cosmetic results in known danger zones (lips, periorificial areas, nose and ears) . Limitations for radical surgical treatment can occur in very large (>2 cm. in diameter) and thick (> 6 mm. in thickness) invasive tumours, with high-risk characteristics, in order to guarantee adequate excision margins (6-10 mm.). Multiple and recurrent cSCCs affecting the head-and neck area can also pose some technical difficulties for surgical treatment and require extensive surgery and plastic reconstruction . Patient’s age, comorbidities, functional status and concomitant medication can negatively impact indication to surgery. Inoperable cSCCs due to patient-based factors or locally advanced tumours can be treated with radiotherapy, either as an elective or as an adjuvant treatment option .
The elderly population is at the highest risk to develop cutaneous melanoma (CM).
In melanoma, current CPGs consider patient age and overall performance status (ECOG) as a relevant factor for guiding clinical management and treatment decisions in elderly patients [90,91]]. In the elderly patient, dermato-oncologists are frequently confronted with several clinical scenarios across all different stages of MM, which could clearly benefit from an integrated, oncogeriatric approach. Despite recommendations in the CPGs, few observational or interventional studies have reported the impact of oncogeriatric factors in the clinical management of primary cutaneous melanoma . Furthermore, the treatment landscape of loco-regional (stage III) and advanced, metastatic disease (stage IV) is rapidly changing, due to recent advancements in selective, molecular-targeted treatment strategies and in immunotherapy of melanoma. Key-areas for an oncogeriatric intervention in the clinical management of melanoma are summarized in Table 3.
The CGA can assess the needs of the patients, the degree of self-sufficiency, the biological age compared chronological age, physical and cognitive performance, but what may be more beneficial in assessing skin cancer patients? We believe that considering the new treatments and the progressive increase of disease-specific outcomes, probably the most important parameters in the assessment of elderly patients with skin cancer is quality of life in combination with life expectancy. The term “quality of life” encompasses the subjective state and capability to act in the physical, mental and social realm. It is the perception of the effects of illness and treatment on the physical, psychological and social aspects of life . In the last 20 years’ patient reported Quality of life (QoL) assessment has become an increasingly important factor in the global assessment of many disease, including cancer . Moreover, the impact of cancer on Health-related quality of life (HRQOL) is poorly understood because of the lack of baseline HRQOL status before cancer diagnosis, or because it is not compared to individuals without cancer. The impact of cancer is often estimated in terms of clinical endpoints such as the risk of recurrence and the probability of remission and survival; but these measures don’t fully capture the impact of cancer in terms of its effect on a person’s functioning and well-being. It’s not easy make studies on elderly oncological patients based on HRQOL, in particular among those with other chronic conditions that likely also affect HRQOL . So, to assess changes in HRQOL that are mainly attributable to the cancer and that are less likely related to other potentially confounding characteristic, pre-diagnosis assessments and comparisons of cancer patients with appropriate control groups are need [118,119]. A study examined the impact of a new cancer diagnosis on HRQOL among older Americans, in 2009 was the first study to report HRQOL changes from before to after cancer diagnosis across most cancer site . The assessment of quality of life constitutes an important endpoint in health services research. It has been established in general oncology, while it has only recently become a focus of interest in dermatologic oncology [121,122]. The impact of NMSC on patients may arise from the tumor itself or as a result of treatment, and trough symptoms, functional limitations, cosmetic burden and auxiliary considerations such as cost and disturbance to the activities of daily living. Many NMSC appear on the face or other visible areas of the skin, it could be symptomatic, with bleeding, pain and pruritus . Moreover, most NMSC are treated with surgery, interrupting the normal activities of daily living, and have a financial impact, and repeated treatments may be needed in the setting of incomplete surgical margins or recurrence. After treatment, there are cosmetic and functional sequelae from scarring that can affect psychosocial function, this burden was assessed using a variety of outcome measures.
A major limitation for an oncogeriatric approach in Dermato-oncology is the lack of validated and optimized clinical tools for the screening and comprehensive assessment of the elderly patient. In current CPGs, there is no guidance or specific evidence to support one or more clinical tools for the oncogeriatric screening or assessment of the elderly patients with NMSC. Onco-geriatric patient evaluation should ideally focus on rapid, easy to administer and validated clinical tools, to adapt to the real-life conditions of dermatological care settings, which are often characterized by high-patient numbers and limited consultation-time. This is especially relevant for the care of NMSC patients, which are a highly heterogeneous patient group, presenting a wide disease spectrum, in terms of morbidity and low disease-specific mortality . In the case of head-and neck cancers, oncogeriatric screening tools (G-8, VES-13) followed by the comprehensive geriatric assessment (CGA) has been used to screen and prospectively evaluate vulnerable patients during radiotherapy . In the elderly, frail patient with high-risk NMSC, future prospective studies should ideally evaluate the impact of an oncogeriatric intervention on treatment decisions, selected clinical outcomes and relevant patient-reported outcomes. In cutaneous melanoma, age-related inequalities in the clinical management could be potentially overcome with a more accurate, interdisciplinary clinical assessment of the elderly patient, effectively differentiating “fit” from “frail” patients. Current CPGs do recommend an oncogeriatric intervention mainly in the setting of advanced, metastatic disease, but, as discussed previously, several practice gaps persist in the clinical management of primary tumours and high-risk loco-regional disease. Since the number of elderly patients with CM will greatly expand in the near future, the clinical need for equal and effective surgical and medical management will likewise increase. Future clinical studies should ideally target the elderly population with CM at high-risk of recurrence as well as with metastatic disease, elucidating the interaction between immunotherapy and the aged immune system. In conclusion, a geriatric and patient-based treatment approach in dermato-oncology could be valuable for stratifying the elderly patient with skin cancer across all available treatment options, optimizing treatment outcomes, quality of life and compliance, while addressing the socio-economic aspects of cancer care.