Background: Tumor fibrosis is essential for defining outcome of patients with various solid tumors. The major pathological signature of tumor fibrosis is a fibrous connective tissue formed by proliferation and activation of fibroblasts and increased synthesis and deposition of fibrillar collagens (type III collagen) leading to immune exclusion and high interstitial pressure in the tumor microenvironment. Recently, the USA FDA issued a Letter of Support to encourage the further study and use of the biomarker PRO-C3 (type III collagen pro-peptides) as a proposed prognostic biomarker of risk of survival outcomes in clinical trials of patients with solid tumors (https://www.fda.gov/media/169332/download). Here we summarize the published data that supports the use of PRO-C3 as a prognostic biomarker that reflects fibrotic activity in the TME. Methods: A PubMed search was used to find studies with PRO-C3, cancer and survival outcome. The hazard ratios (HR) with 95% confidence intervals (95%CI) calculated from univariate cox regression analyses for overall survival (OS) outcomes were collected for where patients were dichotomized based on their pre-treatment PRO-C3 levels and results summarized across indications including breast cancer, pancreas cancer, colorectal cancer, hepatocellular carcinoma, biliary tract cancer and malignant melanoma. Results: Nine studies were retrieved. Table 1 shows the studies with HR and 95%CI for OS after dividing patients into high and low PRO-C3. Various cutoffs were used in the different indications. In all studies, high levels of PRO-C3 were predictive of poor OS with an increased risk of dying ranging 48%-337%. Conclusions: Type III Collagen pro-peptides (PRO-C3) are prognostic for poor OS across indications. These data suggest that quantifying tumor fibrosis is important for prognostication of patients with cancer and that this can be assessed non-invasively in serum or plasma across indications.