Melanoma Matters: Recognizing Risk, Acting Early, and Advancing Care

Melanoma remains one of the most clinically significant skin cancers due to its potential for aggressive progression and metastasis; however, recent advances in early detection strategies, prevention efforts, and immunotherapy have transformed outcomes for many patients. In this discussion honoring Melanoma and Skin Cancer Awareness Month, Jasmin Hundal, MD, MS, MPH, Hematology/Oncology Fellow at the Cleveland Clinic, sits down with OncData Editor in Chief Dr. Matthew Hadfield, Assistant Professor of Medicine at Brown University, to highlight the importance of melanoma and skin cancer awareness, including strategies for detection, risk reduction, and treatment.

Recognizing the Warning Signs

Early detection remains the cornerstone of melanoma management, with a substantial proportion of cases diagnosed at a localized stage. Dr. Hadfield emphasizes the importance of patient awareness and clinician vigilance in identifying suspicious lesions.

Patients with a family history of melanoma represent a high-risk group requiring regular dermatologic surveillance. “First degree relatives with a diagnosis of melanoma should prompt you to want to reach out to your primary care physician and be referred to a dermatologist,” he noted. He also underscores the importance of self-monitoring, particularly for new or evolving lesions.

The widely accepted ABCDE criteria remain a critical clinical tool:

• Asymmetry: “If you have a freckle or a mole that's growing in size, if it's asymmetrical, that should be concerning.”

• Border irregularity: Ragged or uneven edges may indicate malignancy.

• Color variation: “If you see different shades of color, that should be concerning.”

• Diameter: Lesions larger than approximately 6 mm warrant evaluation.

• Evolving: If it's changing shape and/or getting bigger, prompt assessment is essential.

Dr. Hadfield stresses that melanoma often presents as a long-standing mole that undergoes change over time, reinforcing the need for ongoing patient education and routine skin examinations.

Clinical Presentation and Disease Heterogeneity

Melanoma most commonly arises in sun-exposed areas; however, its presentation can be highly variable. “You can develop melanoma on any part of your body,” Dr. Hadfield explained, noting that while cutaneous melanoma is most common, clinicians must remain aware of atypical presentations.

He highlights that melanoma can occasionally regress at the primary site and present as metastatic disease elsewhere. Cases have been identified incidentally during endoscopic procedures, including findings in the colon or pancreas. “Melanoma certainly does weird things,” he remarked, emphasizing the importance of maintaining a broad differential diagnosis in atypical clinical scenarios.

Encouragingly, more than half of melanomas are diagnosed at a localized stage and can be effectively managed with surgical approaches such as Mohs surgery or wide local excision. Additionally, acral melanoma—affecting the palms, soles, or nail beds—remains an important subtype that may present with atypical features and requires heightened clinical suspicion.

The Critical Role of Sun Safety

Preventive strategies are central to reducing melanoma incidence, which has steadily increased over the past two decades. Ultraviolet (UV) radiation exposure remains the most significant modifiable risk factor.

“We know that sunburn predisposes people to a risk of melanoma,” Dr. Hadfield stated. Both acute sunburns and chronic sun exposure contribute to melanoma and other skin cancers. As such, consistent sun protection is essential.

Recommended strategies include:

• Routine use of broad-spectrum sunscreen

• Protective clothing and hats

• Minimizing direct sun exposure, particularly during peak hours

• Avoidance of tanning beds and artificial UV exposure

Dr. Hadfield underscores that “even small sunburns can be dangerous,” reinforcing the importance of prevention messaging across all age groups.

Advances in Immunotherapy and Targeted Treatment

The therapeutic landscape for melanoma has evolved dramatically over the past 15 to 20 years. Historically, metastatic melanoma was associated with poor outcomes, with median overall survival less than a year. However, the advent of immune checkpoint inhibitors has significantly improved survival.

“These therapies take the brakes off the immune system,” Dr. Hadfield explained, enabling T cells to recognize and eliminate tumor cells more effectively. As a result, median overall survival for metastatic melanoma has increased to nearly 10 years, representing a paradigm shift in outcomes and raising the possibility of long-term disease control or functional cure in a subset of patients.

Targeted therapies have further expanded treatment options. Approximately 50% of patients harbor BRAF mutations, making them eligible for BRAF-targeted therapies, typically used in second-line or combination strategies.

Despite these advances, challenges remain. “50% of patients unfortunately don't have that type of response,” Dr. Hadfield noted, highlighting the need for continued innovation.

Emerging Therapies and Future Directions

Ongoing research efforts are focused on overcoming resistance to immunotherapy and addressing tumors with “cold” immune microenvironments. Dr. Hadfield highlights several promising approaches, including oncolytic viral therapies such as RP1 and novel immunotherapeutics like bispecific T-cell engagers targeting PRAME.

While melanoma has led the field in immunotherapy success, progress in other modalities such as antibody-drug conjugates (ADCs) has been limited. “We haven't had the revolution of ADCs, chemotherapy has never really worked very well in melanoma,” he explained. Nevertheless, emerging immune-based strategies offer hope for patients who do not respond to current treatments.

The Importance of Patient Advocacy and Timely Care

A recurring theme in Dr. Hadfield’s discussion is the importance of patient advocacy and timely intervention. Delays in dermatologic evaluation can lead to disease progression, particularly in healthcare systems with limited access to specialists.

“If you think something is suspicious on your skin, the time to go see someone is then, when you notice it,” he advised. Patients should be encouraged to advocate for themselves, as delays in referral and diagnosis can significantly impact outcomes.

Key Takeaways

• Early detection saves lives: Use ABCDE criteria and promptly evaluate suspicious lesions.

• Prevention matters: UV exposure and sunburn significantly increase melanoma risk.

• Immunotherapy has transformed care: Survival in metastatic melanoma has improved dramatically.

• Targeted therapies expand options: BRAF mutations guide treatment in ~50% of patients.

• Unmet needs remain: Many patients do not respond to current therapies.

• Timely evaluation is critical: Encourage patient advocacy to avoid diagnostic delays.

About the Speakers

Jasmin Hundal, MD, MS, MPH, is a third-year Hematology/Oncology Fellow at the Cleveland Clinic in Cleveland, Ohio. Previously, she completed her Internal Medicine Residency at the University of Connecticut. Dr. Hundal’s main area of interest is the overlap between cardiometabolic health and cancer, particularly for breast cancer patients and survivors. Outside of work, she enjoys traveling, cooking, and hiking.

Matthew Hadfield, DO, is a Medical Oncologist and Assistant Professor of Medicine at Brown University/Legorreta Cancer Center. He recently completed his Hematology/Oncology Fellowship at Brown University. Dr. Hadfield’s clinical and research interests are in phase 1 clinical trials and developmental therapeutics, as well as treatment of cutaneous malignancies and management of immunotherapy-related adverse events.