Tumor-to-tumor metastases: systematic review and meta-analysis of 685 reported cases

Tumor-to-tumor metastasis is an exceedingly rare phenomenon where secondary deposits of a tumor develops in another one. Our systematic review and meta-analysis aims to uncover and analyze reported cases to enhance our understanding and improve patients' care. A comprehensive search of the literature was conducted to identify 685 cases of tumor-to-tumor metastasis from 543 articles. Key information, including the donor and recipient organs, tumor histology, primary to metastasis time interval, presence of distant metastases and overall survival was extracted and analyzed. The highest incidence of tumor-to-tumor metastasis was observed in breast cancer and lung cancer metastasizing to meningioma (n = 52, 7.6%; n = 49, 6.2%; respectively). There were 131 (19.2%) autopsy cases, 477 (69.6%) cases diagnosed in vivo, and in 77 cases (11.2%), the timing of diagnosis was unavailable. Death of the patient (including autopsy cases) was reported in 256 (37.4%) cases. In 160 (23.35%) patients, the primary of the metastasis (POM) was occult at the time of metastasis, and in 385 (56.2%) cases, the POM was already known. The median period between clinically overt primary cancer diagnosis and tumor-to-tumor metastasis was 2.0 years. Donor metastases to other sites were observed in 328 (47.9%) cases. In multivariate Cox regression analysis, the primary-to-metastasis interval (< 3 vs > 3 years, HR 2.01, 95% CI 1.18-3.43, p = 0.01) and the presence of donor metastases to other sites (present vs absent; HR 0.37, 95% CI 0.23-0.59, p < 0.001) were significantly associated with survival. In summary, our findings emphasize the necessity for heightened clinical vigilance, early detection, and tailored management to effectively address this unique and challenging clinical scenario.