Spontaneous Regression of Lung Carcinoma: An Essential Review

Abstract

Lung cancer is the second leading cause of cancer in both males and females in the United States, as it has been estimated that 200,000 new cases will appear in males and females in the U.S, accounting for 14% of new cancers. Lung cancer accounts for 25% of cancer fatalities and has the lowest survival rates. Cancer Spontaneous Regression (SR) is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and is a very rare phenomenon of unknown mechanism. The exact incidence of cancer SR is unknown. 176 cases of cancer SR have been reported from 1900 to 1964 with an assessed incidence of 1/ 60,000-100,000 cancer patients, whereas another research found total 15 cases from 1954 to 1997, and more recently 741 cases of SR of malignant diseases in the literature between 1900 and 1987 have been recorded. SR cases concerned several types of malignancies such as lymphoma, leukemia, retinoblastoma, neuroblastoma, melanoma, choriocarcinoma, renal, bladder, and breast cancer, and represented 69% of all SR cases, whereas lung cancer SR only observed in 2.6% of all patients with SR. A few cases reported that SR is an extremely rare biological event in primary lung cancer, and in particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. The SR incidence of advanced NSCLC is relatively low, as approximately 20 cases were recorded from 1950 to 2004, and no more than 15 new cases have been reported in the last 12 years. 10 articles describing NSCLC SR between 1997and 2018 have also been observed. Currently, 17 well-documented case reports of lung cancer SR concerning NSCLC and small cell lung cancer (SCLC) have been described. A total of 25 cases of lung cancer were identified between 1987and 2020. Squamous cell carcinoma (SQCLC) accounted for 10 cases, followed by NSCLC not otherwise defined and adenocarcinomas. The pathogenesis of SR cancer is poorly understood, however recent investigations revealed the role of immunological mechanisms, consequently indicating possible therapy options by specific immunotherapy in the future. It has also been supposed that there may be an immunological association between the stimulus of the biopsies and the SR. Recent researches have shown that immunological reaction can be initiated by trauma to an anatomic location. In some cases the tumor SR became evident only after the tissue biopsy, observation that leads to the option that immune response to the surgical procedure seems to be a plausible contributor to the SR. Para-neoplastic sensorimotor neuropathy (PNS) has been suggested as a mechanism of SCLC and NSCLC SR. Specific anti-neuronal auto-antibodies, anti-Hu antibodies, react both to the tumor and nervous system, in patients with sensorimotor neuropathy, and this inflammatory response has been associated with the antitumor immune response. Many cases of SCLC SR have been escorted by neurological symptoms, but no neurological abnormalities were observed. However, the real association between PNS, Hu-antibody and SR of lung cancer still needs to be clarified by further evidence. It has also been recorded that bronchoscopy contributed to SR of lung cancers. Diverse case reports have recorded patients with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple cycles of chemotherapy but then spontaneously remitted, patients with lung squamous cell carcinoma who experienced SR following biopsy without other therapeutic intervention, and patients with lung adenocarcinoma that spontaneously remitted. Almost all case reports described SR of an untreated lung cancer and were diagnosed and histologically confirmed.