Management of NMSC in transplant recipients

The management of NMSC begins before transplantation. An initial screening examination allows one to determine the risk for subsequent skin cancers based on history and clinical findings. Once patients are transplanted, regular follow-ups are recommended mainly at one year intervals. For patients with a higher load of NMSC, shorter intervals of six or even three months should be observed. These consultations serve on one hand to educate and motivate the patient to protect themselves from the sun daily, with proper clothing and use of sunscreens, while on the other hand, they allow early non-surgical interventions for lesion-directed treatment with, for example, cryotherapy and field-directed therapy with 5-FU or PDT. 
Over time, increasing numbers of NMSC should be the starting point for initiating systemic chemoprevention by nicotinamide or acitretin, as well as for changes in immunosuppression by replacing calcineurin inhibitors with mTOR inhibitors and moving from azathioprin towards mycophenolate mofetil. 

Mucosal and acrolentiginous melanoma

Mucosal and acrolentiginous melanoma are rare types of melanoma with similar aggressive phenotypes, genetic landscapes, and poor prognosis. Acral lentiginous melanoma is most frequently seen in non-Caucasian individuals accounting for 2-3 % of all melanomas. Advanced age groups, with the mean age at onset of 65 years, are affected mainly by the acral lentiginous type of melanoma. A delayed diagnosis is frequent, and the misdiagnosis rate was found to be higher than 20%. Primary melanoma of the mucous membranes is exceedingly rare and may involve the oral (lips, gingiva, palate) and nasal mucosa, the vulva, and the glans penis. Melanomas in mucosal surfaces initially present as a flat, asymmetric, pigmented macule.  However, given that they are usually recognized late, they may already display a nodular or ulcerative component at diagnosis, indicating an unfavorable outcome.

Dermoscopy has been demonstrated to be a useful and non-invasive technique for diagnosing cutaneous pigmented lesions, including melanoma. Although dermoscopy significantly improves diagnostic accuracy in melanocytic lesions on acral sites, volar skin, the nail unit, and mucosa, it does not show the classical pigment network pattern and other classical dermoscopic features characteristically observed elsewhere on the skin. 

However, certain dermoscopic features such as irregular diffuse pigmentation and the parallel-ridge pattern can be of great help in diagnosing acral lentiginous melanoma. In contrast, irregular lines with variegations in colors, spacing, width, and disruption of parallelism represent dermoscopic clues of nail apparatus melanoma. Concerning mucosal melanoma, dermatoscopic evaluation is based on determining the global pattern and the coloration. The combination of blue, grey, or white color with structureless zones is the strongest mucosal melanoma indicator.

Adjuvant treatment of melanoma

Patients with resected stage III and IV melanoma have a substantial risk of recurrence. The outcomes for patients with metastatic disease have improved dramatically over the past decade due to new systemic therapies. Thus, the next goal has been to improve the outcomes of patients with resected stage III and IV melanoma as well, with the introduction of checkpoint inhibitors and targeted therapy in the adjuvant setting. 

This talk will be a review of the latest clinical trial data, the current adjuvant treatment landscape and its application to clinical practice and expected future progress for the management of early-stage melanoma. 

Anti-PD-1 monotherapy and combined BRAF/MEK inhibitors are currently deemed standard of care for resected stage III melanoma.  

The most recent data can be summarized as follows:

• For stage IIIB (AJCC-7) melanoma, 2-year and 3-year recurrence-free survival is approximately 72% and 65% for nivolumab, 70% and 65.7% for pembrolizumab and 68% and 60% for dabrafenib/trametinib, respectively.
• For stage IIIC (AJCC-7) melanoma, 2-year and 3-year recurrence-free survival is 60% and 53.5% for nivolumab, 60% and 54.3% for pembrolizumab and 59% and 47% for dabrafenib/trametinib, respectively. 
• With the new AJCC-8, adjuvant treatment is recommended for patients with stage IIIB-IIID melanoma and may be considered for patients with stage IIIA melanoma.
  For resected stage IV, nivolumab is the only approved agent.
• 5-years recurrence-free survival for dabrafenib/trametinib is 52%. 
• The longest follow up in adjuvant setting is with ipilimumab with a median overall survival follow up of 6.9 years and a benefit observed in the ipilimumab group of 8.7% difference with placebo.
• Recent results from a phase II clinical trial show promising efficacy for combined ipilimumab and nivolumab as well. 

What are the next challenges, that we are going to discuss here?

• Long-term data are required to determine which therapy has the greatest impact on overall survival, which is a crucial endpoint in adjuvant setting.
• Strategies to reduce treatment-related toxicities.
• To optimize these treatments, prognostic, and predictive biomarkers, as well as strategies to overcome resistance are required.