PURPOSE To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

PURPOSE To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.

Whereas targeted and shotgun sequencing approaches are both powerful in allowing the study of tissue-associated microbiota, the human: microorganism abundance ratios in tissues of interest will ultimately determine the most suitable sequencing approach. In addition, it is possible that the knowledge of the relative abundance of bacteria and fungi during a treatment course or in pathological conditions can be relevant in many medical conditions. Here, we present a qPCR-targeted approach to determine the absolute and relative amounts of bacteria and fungi and demonstrate their relative DNA abundance in nine different human tissue types for a total of 87 samples. In these tissues, fungi genomes are more abundant in stool and skin samples but have much lower levels in other tissues. Bacteria genomes prevail in stool, skin, oral swabs, saliva, and gastric fluids. These findings were confirmed by shotgun sequencing for stool and gastric fluids. This approach may contribute to a more comprehensive view of the human microbiota in targeted studies for assessing the abundance levels of microorganisms during disease treatment/progression and to indicate the most informative methods for studying microbial composition (shotgun versus targeted sequencing) for various samples types.

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Renal cell carcinoma (RCC) represents up to 90% of all kidney tumors, with 30% of patients presenting metastasis at diagnosis while 20-50% of those treated for curable localized disease experience recurrence. A better understanding of RCC biology is necessary to define the most efficient and personalized treatment or develop better antineoplastic drugs. Patient-derived xenografts (PDX) have emerged as one of the most promising approaches for that. This tool was generated by using surgical specimens of 87 patients implanted in immunodeficient NOD/SCID/gamma (NSG) mice, 17 of those subcutaneously and 70 at the renal subcapsular space. A total of 19 PDX developed only after orthotopic implantation and included 15 cases of clear cell RCC subtype, 3 cases of papillary subtype, and one unclassifiable tumor. One case of a PDX of a clear cell RCC recapitulated the phenotype of vena cava tumor thrombus extension that had been diagnosed in the source patient. The overall take rate was 27%, and the time to observed tumor growth varied from 5 to 13 months. An association between tumor growth and take rate was suggested by increasing take rates of 18%, 36%, and 100% among pT1 (pT1a + pT1b), pT3a, and pT3b stage tumors, respectively. PDX take rate was unrelated to tumor size (p =0.071). Patients whose tumor fragments engrafted experienced worse overall survival (OS) than those whose tumor fragments did not engraft (p = 0.003). Data also suggested a similar trend of association with metastasis-free survival (MFS) (p = 0.063). The median MFS for patients with successful PDX was 21.6 months (95% CI: 14.9, 28.3;), compared to a median of 34.4 months (95% CI: 30.4, 38.5 p = 0.003) among PDX engraftment-negative patients. PDX characterization by immunohistochemistry and targeted sequencing of the 21 most frequently mutated genes in the kidney indicated that all PDXs preserved RCC identity and major molecular alterations. From 19 PDX, the sequences of 13 patients’ tumor samples were compared with their respective PDX. In most patients (92% - 11/12), at least one mutation in patients’ tumor was identified in the PDX and in one case, no alterations were mapped. The most frequently mutated genes were VHL (50% - 6/12) and PBRM1 (41.7% - 5/12), followed by SETD2 (25% - 3/12), BAP1 and KDM5C (both 16.7% - 2/12), and ARID1A (8.3% - 1/12), indicating that all PDXs preserved RCC identity and major molecular alterations. These findings suggest that tumor engraftment capacity can identify patients at increased risk of relapse or death. Furthermore, pT1 stage tumors with the ability to engraft could also facilitate the identification of risk factors related to the rare pT1 cases with disease progression. These results suggest that the orthotopic xenograft model of RCC represents a suitable tool to study RCC biology, identify biomarkers, and test therapeutic candidates. Citation Format: Vilma Regina Martins, Adriano Beserra, Ethiene C. Estevan, Stephania Bezerra, Giovana T. Torrezan, Amanda Ikegani, Dellê Humberto, Isabela V. Cunha, Isabella T. Meira, Dirce M. Carraro, Primo N. Lara, Stenio Zequi, Tiago G. Santos. Patient-derived renal cell carcinoma xenografts engraftment identifies patients at risk of disease relapse, progression and death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3097.