The clinical, pathologic, and genetic features in MF and SS are highly heterogeneous with significant inter- and intra-patient variability thus requiring a highly personalized approach to management. The current clinical staging system is inadequate in enabling clinicians to provide optimal risk-stratified, personalized management. Most systemic therapies often have differential activity across disease compartments and different disease profiles, thus in addition to clinical stage, presence of large cell transformation, dynamics of disease progression, compartmental disease severity, and other prognostic or actionable data are important elements that guide clinical management. In CTCL, combination therapies that partner to maximize global response (composite of compartmental responses) and utilization of optimal maintenance therapy strategies should be considered whenever appropriate. The ongoing large-scale international prognostic index project in MF/SS (PROCLIPI), may provide data for evidence-based reshaping of our clinical staging system and establishment of a validated CL prognostic index (CLIPI), that will contribute towards optimizing risk-based clinical management. Given the diverse genomic heterogeneity, we do not yet have molecular data that is used in standard treatment guidelines. However, evolving data supports potential prognostic and/or actionable molecular profiles that can be considered when prioritizing treatments, especially in the relapsed/refractory setting. The unique QOL issues in CTCL may lead to treatment change prior to objective disease progression. Ultimately, in this highly heterogeneous disease where treatments also have selective activity, there is a critical need to establish meaningful biomarkers to better align patients’ disease profile with treatments that would most benefit them, help to prioritize and combine or sequence therapies.
