Renal capsular invasion can predict recurrence of localized kidney cancer

A study published in Scientific Reports indicates that renal capsular invasion (RCI) could be a significant risk factor for recurrence of localized clear cell renal cell carcinoma (RCC). In contrast, lymphovascular invasion (LVI) was not found to be an independent prognostic variable in RCC recurrence following surgery.

The study, led by U-Syn Ha, MD, PhD, from the College of Medicine at The Catholic University of Korea in Seoul, derived data from the Korean Renal Cell Carcinoma (KORCC) database, a nationwide database from eight academic centers in the Republic of Korea.

Several studies that investigated the prognostic value of RCI resulted in substantial inconsistencies regarding the association between RCI and oncological outcomes. In general, the sample size in the studies limited statistical value.

Likewise, there are conflicting results regarding the prognostic significance of LVI for RCC. Metastasis starts with malignant cells accessing the circulation through the blood or lymphatic vessels, and LVI is also an important prognostic factor in other urinary tract malignancies.

The authors evaluated the impact of RCI and LVI on recurrence in a large cohort with of homogenous RCCs. Clinical data collected included preoperative baseline information and laboratory values, surgical information, pathologic data (stage, tumor size, histologic subtype, and RCI or LVI), and postoperative follow-up data (disease recurrence, death, and cause of death).

Specimens were assessed by pathologists at each institution without centralized review. RCI was defined as the presence of tumor cells within the fibrous renal capsule without perirenal fat tissue infiltration; LVI was defined as the presence of tumor cells inside small blood vessels or lymphatic channels within the tumor (excluding the renal vein and its muscle-containing segmental branches).

A total of 6,849 patients who had undergone surgical treatments for RCC were included in the KORCC database. To evaluate the prognostic significance of RCI, 2,733 patients—including 603 patients with RCI (incidence 22.1%)—were enrolled; 120 patients were matched with 600 patients without RCI. Median follow-up durations were 39 months and 31 months in patients with and without RCI, respectively.

To analyze the prognostic value of LVI, 3,586 patients—including 121 patients with LVI (incidence 3.4%)—were enrolled; 61 patients were matched with 306 patients without LVI. Median follow-up durations in patients were 37 months and 34 months in patients with and without LVI, respectively.

In all statistical models, RCI was significantly associated with an increased risk of recurrence.

Among all patients evaluated for RCI, recurrence was observed in 209 (7.6%) total patients, including 75 (12.4%) patients with RCI and 134 (6.3%) patients without RCI.

The 5-year recurrence-free survival rates were 83.5% and 92.4% in patients with and without RCI, respectively. When patients were stratified into 4 groups based on RCI and tumor stage (pT1 and pT2), the 5-year recurrence-free survival rates were 89.4% and 93.7% in pT1 patients with and without RCI, respectively (P < 0.001); the rates were 58.3% and 76.7% in pT2 patients with and without RCI, respectively (P=0.088).

In a separate analysis, LVI was significantly associated with an increased risk of recurrence only in non-adjusted univariate analysis (Hazard Ratio [HR]: 3.642), but not in multivariate adjusted analysis (HR: 1.687) or propensity score matching models.

Recurrence was observed in 236 (15.2%) patients including 29 (24.0%) patients with LVI and 207 (6.0%) patients without LVI.

The 5-year recurrence-free survival rates were 64.7% and 91.3% in patients with and without LVI, respectively (log rank test, P <  0.001). When the patients were stratified into 4 groups based on the LVI and stage (pT1 and pT2), the 5-year recurrence-free survival rates were 69.2% and 93.4% in pT1 patients with and without LVI, respectively (log rank test, P <  0.001); and 53.1% and 71.3% in pT2 patients with and without LVI, respectively (log rank test, P = 0.026) .

The investigators noted that LVI was associated with worse pathologic features, so the positive association between LVI and recurrence in univariate analysis might be due to overall pathologic features. Patients with worse pathology (larger tumor size, higher grade, and sarcomatoid differentiation) were more likely to show positive LVI.

Although the study included a large multi-institutional cohort, the researchers pointed out that it may not be representative of general RCC patients due to the retrospective non-randomized design. Another limitation was that data were analyzed without central pathology review.

“This study showed that RCI in localized clear cell RCC can provide clinically important prognostic information based on the association between RCI and RCC recurrence. On the other hand, LVI did not influence the recurrence of localized clear cell RCC following curative surgery.”

To read more about this study, click here.