Homogeneity in immune features between colorectal liver metastases better identifies patients with good prognosis compared to pathological response to preoperative chemotherapy.

In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes.

Synchronous Metastasis Rates in T1 Renal Cell Carcinoma: A Surveillance, Epidemiology, and End Results Database-based Study.

BACKGROUND: Synchronous metastasis (SM) rates in T1 renal cell carcinoma (RCC) patients relied on historical cohorts and may not take into account the favorable stage migration toward lower tumor size (TS) that occurred in more recent years. OBJECTIVE: To investigate SM rates in T1 RCC patients according to histological subtype (HS), tumor grade (TG), and TS. INTERVENTION: Partial nephrectomy, radical nephrectomy, focal ablation, and non-interventional management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), 60 640 stage T1 patients were identified. SM rates were tabulated and tested in multivariable logistic regression models. RESULTS AND LIMITATIONS: According to HS, average SM rates were 0%, 0.5%, 1.1%, 1.4%, 3.7%, 21.5%, and 36.2% for multilocular cystic, chromophobe, papillary, clear cell TG 1-2, clear cell TG 3-4, collecting duct, and sarcomatoid RCC, respectively. In a multivariate logistic regression model, age, TS, HS, and TG were independent predictors of SM. Bone only was the commonest metastatic site (41.0%), followed by lung only (24.5%), liver only (3.6%), and brain only (3.8%). Of all SM patients, 72.8% harbored a single metastatic site. The major limitations of this study are lack of recurrence and metastatic progression data. CONCLUSIONS: Within T1 RCC, it was possible to identify five metastatic risk categories according to SM rates: (1) multilocular cystic RCC (0%), (2) chromophobe RCC (0-2.0%), (3) clear cell TG 1-2 and papillary RCC, (4) clear cell TG 3-4 RCC (1.2-8.9%), and (5) sarcomatoid and collecting duct RCC (7.0-49.1%). The most frequent metastatic location is bone only, followed by lung only, and virtually all SMs are solitary. PATIENT SUMMARY: Metastatic rate varies in T1 stage renal cell carcinoma patients according to tumor size, histology, and tumor grade.

Comparison of survival outcomes in patients with metastatic papillary vs. clear-cell renal cell carcinoma: a propensity-score analysis.

BACKGROUND: To compare survival outcomes of metastatic patients harbouring either papillary (pRCC) or clear-cell (ccRCC) renal cell carcinoma in overall population and according to treatment modality. METHODS: Within the Surveillance, Epidemiology and End Results database (2006-2015), we identified 6800 patients (585 papillary and 6215 clear-cell) with metastatic RCC. Propensity-score (PS) matching, Kaplan-Meier plots and multivariable Cox-regression models (CRMs) were used. RESULTS: Overall, 585 (8.6%) patients harboured pRCC. Rates of nodal metastases were higher in patients with pRCC (49.7 vs. 23.3%; p < 0.001). Median overall survival (OS) was 13 vs. 18 months for pRCC vs. ccRCC patients. After multivariable adjustments, no difference in OS was recorded. Furthermore, after propensity-score matching, virtually the same results were recorded. Median OS of pRCC vs. ccRCC was 8 vs. 4 months for no treatment (NT), 11 vs. 12 months for targeted therapy alone (TT), 17 vs. 35 months for cytoreductive nephrectomy alone (CN) and 18 vs. 25 months for combination of CN with TT. CONCLUSIONS: Metastatic pRCC patients exhibit poor survival, regardless of treatment received. Moreover, pRCC patients are more likely to present nodal metastases, compared to ccRCC patients, as demonstrated by twofold higher rates of lymph node invasion at diagnosis. These observations indicate that papillary variant represents more prognostically unfavorable tumor histology, in the context of metastatic RCC.