40-year-old Ms. Sun found a pulmonary nodule in the unit’s physical examination, which was a 1.5cm solid nodule. From the appearance, it was not so optimistic, so she decided to perform laparoscopic surgery in a local hospital. The pathology was invasive adenocarcinoma, 60% of the acinar type, 40% of the micropapillary type, and no lymph node metastasis. From the perspective of staging, it belongs to stage IB. This stage is considered to be relatively early lung cancer. According to international and domestic guidelines, it is not recommended. postoperative adjuvant therapy. However, due to the low differentiation of the micropapillary type, Ms. Sun was extremely anxious, and repeatedly asked for genetic testing. In the absence of sensitive gene mutations, she strongly requested chemotherapy.
Lung cancer with an early stage is not recommended for postoperative adjuvant therapy in the guidelines, but there are high risk factors for recurrence and metastasis. Is it really worth noting it? Is there a test to help predict the risk of early-stage lung cancer recurrence and metastasis? Is there any way to judge whether postoperative adjuvant therapy will benefit or not? There is indeed a new method to assist judgment, that is, blood test for MRD.
MRD is minimal residual disease or molecular residual disease. The detection method is to draw blood and use NGS (Next Generation Sequencing) to detect ctDNA. ctDNA refers to single- or double-stranded DNA released by tumor cells into the plasma, which carries molecular genetic changes consistent with the primary tumor tissue. MRD is the main reason for tumor recurrence after radical resection. Many large-scale clinical studies at home and abroad have shown that MRD status based on ctDNA detection is closely related to the risk of recurrence. The MRD indicator was originally used for hematological malignancies, and has gradually been used in solid tumors in recent years.
At the 18th China Lung Cancer Summit Forum in 2021, my country’s first “Consensus on the Detection and Clinical Application of MRD in Lung Cancer” was reached. The consensus pointed out that after radical resection of early-stage non-small cell lung cancer, positive MRD indicates a high risk of recurrence and requires close follow-up management. It is recommended to monitor MRD every 3-6 months.
Recently, the results of a large-scale MRD prospective study on lung cancer jointly conducted by the team of Professor Wu Yilong of Guangdong Provincial People’s Hospital and Jiyinga were listed in the top international journal Cancer Discovery. The study draws several conclusions: 1. The tumor burden in the postoperative MRD-negative population is extremely low (close to cure), and adjuvant therapy may be unnecessary. 2. For patients with positive MRD test before adjuvant therapy after surgery, adjuvant therapy can significantly improve their disease-free survival. 3. Whether ctDNA can be detected before operation does not affect the MRD monitoring after operation. 4. For stage II-III patients with high recurrence risk, the analysis found that the peak of MRD conversion or recurrence occurred at about 18 months after surgery. 5. In patients with single brain metastases, the results of MRD monitoring will be affected due to the existence of the blood-brain barrier. 6. The prognosis of patients with negative single node detection after operation is significantly better than that of positive patients.
At present, MRD is considered to be a marker leading a new era of lung cancer treatment. It predicts prognosis in advance at the molecular biological level and guides the need for adjuvant therapy, especially for early stage IA. For lung cancer, whether adjuvant chemotherapy or adjuvant targeted therapy should be used, MRD can be used to help judge.