Pulmonary lesion after surgery for renal cancer: progression or new primary?

Purpose: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). Methods: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM +. Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. Results: 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55 months [32.8–107.2] vs. 20 months [9.0–45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1–4] vs. 1[1–1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20 mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70–0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97–1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01–1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06–1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07–1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07–1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04–1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01–1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM +. Furthermore, number (OR:1.08; 95% CI 1.04–1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09–1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM +. Survival analysis showed a median second PFS of 10.9 years (95% CI 3.3-not reached) for LC and a 3.8 years (95% CI 3.2–8.4) for RCCM +. The median OS time was 6.5 years (95% CI 4.4-not reached) for LC and 6 years (95% CI 4.3–11.6) for RCCM +. Conclusions: Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.