Patients with RCCLM generally have a particularly poor prognosis, which is even worse than patients with RCC metastases to other organs, such as lungs and bone.13 In the series of Suppiah et al., the median survival of 186 untreated patients with hepatic RCC metastases was only 7.8 months.13 However, the present population-based study demonstrates that a selected subgroup of patients with RCCLM can be offered the possibility of long-term survival by surgical intervention, either resection or local ablation. Five-year survival of 43% as found in the present study is substantially better than the approximately 10% survival after 1 year reported in the whole group of patients with RCCLM.14,15
Data regarding the efficacy of surgical treatment of RCCLM are rarely reported. In a survival analysis based on 15 reports by Aloia et al., 2-year survival was 40%.9 Besides this review including 64 patients, two other studies have been published.16,17 Thelen et al. described their single-institution experience in 31 patients who underwent liver resection for RCC metastases with an overall 5-year survival of 38%.17 Adam et al. described a series of 1452 patients with noncolorectal, nonneuroendocrine hepatic metastases, of whom 85 had a primary RCC.16 Median overall survival was 36 months, with a 5-year survival rate of 38%.
The reported survival rates in the present study are superior to the results of older series reviewed by Alioa et al., and comparable to the recently published series from Adam et al. and Thelen et al.9,16,17 The improved survival rates in time could well be explained by better patient selection, surgical technique, and perioperative care. Advancements in imaging technology resulting in more adequate staging, and better appreciation of tumor and patient characteristics that influence prognosis have probably contributed to the improved patient selection. Technical improvements in liver surgery during the past decades and improvement of perioperative care have resulted in a safer approach to both minor and major resections.
Prognostic factors predicting long-term survival after resection of RCCLM as described in previous series included male sex, a maximum metastasis diameter of ≤ 5 cm, primary tumor localization in the left kidney, disease-free interval of >24 months, and tumor-negative resection margins.17 The aim of determining such prognostic factors is to establish selection criteria for resection. In our series, only metachronous metastases and radical resection had a positive impact on overall survival in univariate analysis. Surprisingly, extrahepatic disease had no statistically significant impact on survival, with a trend toward improved survival, although patient numbers are small. This finding is in agreement with data from Alioa et al.9 We assume that these patients have only slowly progressive disease with relatively long disease-free intervals between each distant metastasis. Such patients with indolent biological behavior of RCC make them ideal candidates for sequential metastasectomies. Therefore, selection bias is probably the most important explanation for this contradictory finding.
We involved all centers performing liver surgery in the Netherlands. Furthermore, we did a search in the nationwide histopathology database, PALGA, in which all data on resection specimens in the Netherlands are archived. In this manner, we believe that we reliably retrieved data from all patients who underwent surgical treatment for hepatic metastases from RCC in the last 19 years in the Netherlands. This fact addresses another interesting point of this study. From data of the Dutch cancer registry, we know that 30,000 patients were diagnosed with RCC in the study period.1 On the basis of the approximately 10 to 20% of patients with RCC who ultimately developed liver metastases, we can estimate the total number of patients with RCCLM during this time period in the Netherlands.18–21 In the last 19 years, approximately 3000–6000 patients (10 to 20% of 29,627) had hepatic metastases due to RCC. In this particular time period, we identified 33 patients who where surgically treated, which indicates that approximately 0.5 to 1% of the patients underwent surgical intervention. This emphasizes once more the remarkably small proportion of these patients who were treated surgically. The question remains whether it is only this small proportion of patients having an indication for surgical treatment, or whether some patients are not referred by urologists or medical oncologists for treatment, not being aware of the potential impact on survival.
We realize the limitations of this study. Data were obtained from a complete but relatively small group of patients, limiting analysis on prognostic factors because of wide confidence intervals and hampering adequate multivariate analysis. Data were retrieved over a long study period (19 years), during which many novel techniques in imaging, perioperative care, and liver surgery were introduced, as described above. Finally, data were retrieved from 14 hospitals in a retrospective way, with its inherent methodological drawbacks. Hence, care must be taken in drawing strong conclusions from the available data. On the other hand, the relatively good survival rates, despite a large heterogeneity in selection criteria of the different hospitals, together with improvements in liver surgery in the last decade, suggest that even better survival rates could be reached after adequate patient selection.
The survival rates presented in this study and the results of previous studies compare well with the results of hepatic resection for colorectal metastases.9,16,17 Likewise, these survival rates are also certainly not inferior to results after resection of pulmonary metastases in patients with RCC. The outcomes of surgery on RCC metastases to the lungs have been well investigated. Several relatively large series, although retrospective and nonrandomized, emphasize a survival benefit, and the possibility of long-term survival (up to 37% 5-year survival rate) after radical resection in selected patients with relatively few complications.7,22,23
An aggressive surgical approach to these pulmonary metastases, in which a radical resection can be achieved, is currently considered as the appropriate treatment. The future will tell whether surgical treatment for RCCLM will achieve the same status as in treatment of RCC lung metastases. Although molecularly targeted therapies have resulted in marked survival benefit in metastatic RCC, they do not provide the possibility of long-term survival. The results of this study, and of comparable reports in literature, presume a wider indication for liver resection in patients with RCC, and deny the suggestion that patients with RCCLM cannot be cured. Future research should also further define the role of molecularly targeted therapy in possible (neo)adjuvant therapies.
In conclusion, surgical treatment of hepatic metastases from RCC is only performed in approximately 1% of patients. Data from this study, in accordance with data from almost 150 patients reported in the literature, suggest that surgical treatment can provide favorable survival rates, with a 5-year survival of 43%. The present data on survival rates after surgery, combined with the unavailability of effective systemic therapies, justify an aggressive surgical approach in patients with hepatic metastases from RCC when a margin-negative resection can be obtained.