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Impact of Circulating and Tissue Biomarkers in Adjuvant and Neoadjuvant Therapy for High-Risk Melanoma: Ready for Prime Time?

ABSTRACT: The prognosis of patients with metastatic melanoma has substantially improved over the last years with the advent of novel treatment strategies, mainly immune checkpoint inhibitors and BRAF and MEK inhibitors. Given the survival benefit provided in the metastatic setting and the evidence from prospective clinical trials in the early stages, these drugs have been introduced as adjuvant therapies for high-risk resected stage III disease. Several studies have also investigated immune checkpoint inhibitors, as well as BRAF and MEK inhibitors, for neoadjuvant treatment of high-risk stage III melanoma, with preliminary evidence suggesting this could be a very promising approach in this setting. However, even with new strategies, the risk of disease recurrence varies widely among stage III patients, and no available biomarkers for predicting disease recurrence have been established to date. Improved risk stratification is particularly relevant in this setting to avoid unnecessary treatment for patients who have minimum risk of disease recurrence and to reduce toxicities and costs. Research for predictive and prognostic biomarkers in this setting is ongoing to potentially shed light on the complex interplay between the tumor and the host immune system, and to further personalize treatment. This review provides an insight into available data on circulating and tissue biomarkers, including the tumor microenvironment and associated gene signatures, and their predictive and prognostic role during neoadjuvant and adjuvant treatment for cutaneous high-risk melanoma patients.

SUBMITTER: Indini A

PROVIDER: S-EPMC8200339 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Liquid biopsies are the detection of molecular information in fluids from patients with cancer. In colorectal cancer (CRC), the most promising liquid biopsy strategy is the use of circulating tumor DNA (ctDNA) from plasma. In early-stage CRC, the potential for ctDNA to impact care stems from the detection of minimal residual disease (MRD) to guide adjuvant therapy after curative intent treatment and in identifying recurrences during surveillance. As for any new diagnostic test, ctDNA assays must overcome pre-analytical and analytical challenges before clinical implementation. We will discuss important logistical and assay considerations that clinicians and patients should understand when assessing ctDNA assays. We will also delve into important concepts to aid in interpreting ctDNA results and potential incidental findings that may arise. Sequencing errors, germline variants, and clonal hematopoiesis of indeterminate potential (CHIP) must be addressed to properly interpret results. CHIP is also an important consideration that impacts patient prognosis through association with cardiovascular and hematologic diseases. With this background in place, we next review the best available evidence for the use of ctDNA in early-stage colon cancer. Observational cohorts have established MRD after surgery as a significant prognostic factor for recurrence in stage II and III colon cancer. It also has the ability to anticipate clinical recurrence before standard investigations when used in surveillance. The first and only interventional randomized trial to date evaluating ctDNA is DYNAMIC. The study demonstrated the noninferiority of a MRD detection-guided approach in selecting patients with stage II colon cancer for adjuvant treatment. Notwithstanding the important results, there are still important questions to be answered before ctDNA enters prime time in the clinic. However, future appears bright and ongoing trials will help clarify how to best use this technology in early-stage colon cancer.

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Impact of Circulating and Tissue Biomarkers in Adjuvant and Neoadjuvant Therapy for High-Risk Melanoma: Ready for Prime Time?

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