Our study involved the analysis of a case in which a site of metastasis of ccRCC significantly decreased in size before initiation of any type of cancer treatment. Subsequently, we conducted a review of similar case reports in the literature using OVID Medline. To be included in our review, cases of spontaneous regression had to involve a ccRCC diagnosis confirmed by histology of the area of regression. A total of 30 cases, including our own, were included in the final analysis.
Theories explored in the analysis of prior case reports involved increased involvement of the immune system in ccRCC compared to other types of malignancy, inhibition of angiogenesis by reducing angiogenic factors through the destruction or removal of the primary tumor leading to necrosis, and the use of antibiotics for unrelated bacterial infections modifying the tumor microenvironment. In our case specifically, we postulate that the diagnostic biopsies of the paraspinal muscle mass and primary tumor led to the release of tumor-specific antigens into the bloodstream, thus priming exposure to the patient’s immune system. Furthermore, the patient received antibiotic treatment prior to spontaneous regression, which could have impacted the microbiome and immune system recruitment. These factors collectively were considered likely contributors to the spontaneous partial regression of the paraspinal muscle mass.
Another theory not elaborated upon could include a simulated decrease in angiogenesis caused by decreased blood flow to the malignancy. The patient was also noted to have moderate anemia, with a hemoglobin level of 9.6 g/dL, which could theoretically impact areas of malignancy by reducing blood supply in a manner analogous to diminished angiogenesis. Next-generation sequencing of the paraspinal muscle mass identified a mutation in the Von Hippel-Lindau (VHL) gene, specifically in Exon 2, along with a mutation in the Polybromo-1 (PBRM1) gene. VHL is a well-characterized tumor suppressor gene involved in regulating hypoxia-inducible factor (HIF) signaling, and its dysfunction is commonly associated with tumorigenesis in clear cell renal cell carcinoma (ccRCC). PBRM1, another tumor suppressor gene, plays a critical role in chromatin remodeling and modulation of the tumor microenvironment and is recognized as an important prognostic marker. These genetic alterations may have contributed to an increased likelihood of spontaneous regression, although further research is needed to clarify their exact roles and mechanisms in this process.
This investigation provides a significant contribution to the understanding of spontaneous regression in ccRCC. Unlike most reported cases, where spontaneous regression was observed following nephrectomy, this case uniquely demonstrated regression after a minimally invasive biopsy. This finding raises the possibility that physical disruption of a malignant mass may not require a major surgical procedure to elicit regression. Further research is warranted to explore the critical role of the tumor microenvironment in facilitating spontaneous regression, uncover its underlying mechanisms, and potentially harness these processes for the development of innovative therapeutic strategies in the treatment of ccRCC.
Written by:
- Adanma Ayanambakkam, MD, Assistant Professor, GU Medical Oncology & TSET Phase 1 Program, Associate Program Director, Hematology Oncology Fellowship Program, Medical Director, Infusion Services, Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK
- Anoushka Mullasseril, MD, Department of Internal Medicine, University of Oklahoma Health Sciences, Oklahoma City, OK