Cutaneous squamous cell carcinoma (CSCC) is a common skin cancer originating in squamous cells, flat cells in the epidermis. While most CSCC cases are treatable when detected early, “advanced” CSCC means the cancer has grown deeply into surrounding tissues, spread extensively locally, or metastasized to distant parts of the body. This progression makes advanced CSCC more challenging to manage. This article provides an understanding of advanced CSCC, its diagnosis, treatment options, and long-term management.
Understanding Advanced CSCC
Advanced CSCC is characterized by its aggressive nature, often involving local invasion and metastasis. Local invasion means the cancer has grown into deeper structures like underlying fat, muscle, nerves, or bone, potentially causing disfigurement or compromising these structures. Perineural invasion, where cancer grows along nerves, is a specific type of local invasion that can lead to numbness, pain, or muscle weakness.
Metastasis occurs when cancer cells spread from the primary tumor site to other areas of the body, such as nearby lymph nodes or distant organs. Regional lymph nodes, especially in the head and neck, are common sites for CSCC metastasis, with spread occurring within two to three years of initial diagnosis. Common signs indicating advanced disease include a rapidly growing or large lesion, persistent ulceration, bleeding, or a noticeable lump in nearby lymph nodes.
Several factors increase the risk of developing advanced CSCC:
A compromised immune system, due to conditions like HIV, chronic lymphocytic leukemia, or immunosuppressive medications following organ transplantation.
A history of chronic wounds, such as burns or scars.
Previous radiation therapy in a specific area.
Tumor diameter greater than 2 centimeters.
Thickness exceeding 6 millimeters.
Invasion beyond subcutaneous fat.
Poor differentiation of cancer cells.
Involvement of the ear, temple, or lip as the primary site.
Diagnostic Approaches
Diagnosing and staging advanced CSCC begins with a thorough physical examination and an initial biopsy. A biopsy, such as a punch or excisional biopsy, confirms the presence of cancer and provides details about its characteristics, including depth and cell differentiation.
Imaging studies are then performed to determine the full extent of the disease. Computed tomography (CT) scans are used to assess for bone or soft tissue invasion and to check for metastasis in cervical lymph nodes. Magnetic resonance imaging (MRI) is preferred for evaluating perineural invasion, where cancer cells spread along nerves, and for assessing orbital or intracranial extension. Positron emission tomography (PET)/CT scans can provide additional information about distant metastases.
The American Joint Committee on Cancer (AJCC) staging system classifies the severity of CSCC, guiding treatment decisions. This system considers the tumor’s size and extent (T), whether it has spread to nearby lymph nodes (N), and if it has metastasized to distant organs (M). Advanced CSCC is classified as Stage III or Stage IV, indicating more extensive local invasion or the presence of metastasis.
Treatment Strategies
Treatment for advanced CSCC often involves a multidisciplinary approach, combining various modalities to achieve the best possible outcome. The specific strategy depends on the tumor’s location, size, depth of invasion, and whether it has spread.
Surgical removal is a primary treatment option for many advanced CSCC cases. For certain tumors, especially those on the head and neck where preserving healthy tissue is important, Mohs micrographic surgery may be used. This precise technique involves removing thin layers of cancerous tissue and examining them under a microscope until all cancer cells are gone, minimizing damage to surrounding healthy skin. For larger lesions, wide local excision, which removes the tumor along with a margin of healthy tissue, may be performed. Reconstructive surgery might be necessary after extensive excisions to repair the affected area.
Radiation therapy is another treatment modality used for advanced CSCC. It can serve as a primary treatment option, particularly for tumors difficult to remove surgically, or for elderly patients not candidates for surgery. Radiation can also be used as adjuvant therapy, given after surgery to eliminate any remaining cancer cells and reduce recurrence risk. In cases where cancer has spread and is causing symptoms, radiation therapy can be used for palliative care to manage pain or reduce tumor size, improving quality of life.
Systemic therapies, which treat cancer throughout the body, have significantly advanced the management of advanced CSCC. Immunotherapy, particularly with checkpoint inhibitors like cemiplimab (Libtayo®) and pembrolizumab (Keytruda®), has emerged as a significant advancement. These drugs work by blocking proteins, such as PD-1, that cancer cells use to hide from the immune system, helping the body’s own immune cells recognize and attack the cancer. Cemiplimab and pembrolizumab are approved for patients with advanced CSCC who are not suitable for curative surgery or radiation.
Targeted therapy involves drugs that specifically target genetic mutations or proteins within cancer cells, disrupting their growth. While less commonly used than immunotherapy for advanced CSCC, these therapies may be considered if a relevant genetic alteration is identified. Chemotherapy is now often reserved for particular circumstances or when other treatments are not suitable. The decision-making process for advanced CSCC treatment involves a team of specialists, including dermatologists, oncologists, surgeons, and radiation oncologists, to create a personalized treatment plan.
Outlook and Ongoing Management
The outlook for individuals with advanced CSCC varies considerably, influenced by factors such as the extent of the disease, the patient’s overall health, and their response to treatment. While early-stage CSCC has a high five-year survival rate, advanced cases, especially those with lymph node involvement, may have a five-year survival rate ranging from 25% to 45%. Newer treatments, particularly immunotherapies, have improved outcomes for many patients.
Ongoing management is a continuous process following initial treatment, focusing on surveillance for recurrence and the development of new lesions. Regular follow-up appointments are scheduled every six to twelve months for patients with a history of CSCC, and more frequently for those with extensive histories or aggressive tumors. These appointments involve comprehensive skin examinations, including inspection and palpation of the treated area, regional lymph nodes, and the entire skin surface.
Surveillance imaging, such as CT or MRI scans, may be performed periodically to monitor for any signs of recurrence or spread, particularly in higher-risk cases. Palliative care plays a role in managing symptoms and improving the quality of life for individuals with advanced CSCC, addressing pain, discomfort, and other challenges associated with the disease. This type of care can be provided alongside active cancer treatments.
All patients, even after successful treatment, are encouraged to practice sun protection to reduce the risk of future skin cancers. This includes using broad-spectrum sunscreen with an SPF of at least 15 for daily activities and SPF 50+ for extended outdoor exposure, wearing protective clothing, and seeking shade. Performing regular skin self-exams is also advised to identify any new or changing growths early, allowing for prompt evaluation by a healthcare provider.