Despite many studies demonstrating equivalent oncology efficacy between RN and PN in treating RTs ≤ 4cm and select tumors ≤ 7 cm,12-14
RN remains the most common form of treatment for newly diagnosed small RTs.8, 9
In this study as well as other population-based studies, fewer than 1 in 5 patients with RTs ≤ 4 cm are treated with PN.8
During the last decade there has been a paradigm shift at specialized medical centers in the United States, where elective PNs now account for up to 60% of all nephrectomies.15, 16
This trend toward organ preservation, similar to other solid malignancies such as breast cancer and soft-tissue sarcomas, is a result of improvements in surgical techniques, advances in the understanding of the biology of RTs, and an increasing awareness of the importance of preserving long-term kidney function.
Several studies have demonstrated poor kidney functional outcomes in patients treated with RN rather than PN.17, 18
Recently, we demonstrated that even in the setting of a normal baseline serum creatinine and two normally functioning kidneys, patients undergoing RN for a solitary small RT (≤4 cm) had a statistically significant greater risk of developing CKD after surgery (HR 3.8, P<0.0001). The 3-year probability of freedom from new onset of CKD was only 35% in patients who received RN compared with 80% in patients who received PN (P<0.0001).7
The clinical significance of iatrogenic CKD has been poorly studied and remains an investigational topic of great importance. Emerging evidence suggests that the type of treatment for small RTs may have a significant effect on morbidity and mortality. In a recent series from the Mayo Clinic, younger patients (<65 years of age) treated with RN instead of PN for pT1a tumors had a significantly increased risk of mortality after adjusting for preoperative variables associated with mortality.16
In our study, we examined a population-based cohort of patients aged 65 years and older. Patients treated with RN instead of PN for small RTs developed significantly more CV events over time and had a significantly greater risk of death from any cause. No significant differences, however, were observed between the two groups in the hazard of either a first CV event or CV-related death.
Although these results seem incongruent, they are consistent with data from other studies examining the relationships between CKD, CV disease, and mortality. CKD may be a greater risk factor for recurrent
CV events than for the onset of a first CV event.19
In addition, CKD and CV disease appear to act as strong independent risk factors, as opposed to synergistic risk factors, for mortality.20
Thus, it is not surprising to find that patients undergoing RN have an increase in the cumulative number of CV events and in all-cause mortality, but no increase in the risk of a first CV event or CV death.
Several limitations of this study warrant mention. The largest is the lack of randomization and the possible influence of selection bias on the observed differences in survival and CV events between the cohorts. To minimize the effect of selection bias, we controlled for demographic and comorbid factors that would be expected to influence both treatment choice and outcomes. Unfortunately, the only way to eliminate this bias would be to prospectively randomize patients to RN or RN, a study many would consider unethical today.
Another limitation is the lack of information on pre- and postoperative kidney function. Although Medicare claims provided data on important and relevant comorbidities, serum creatinine levels for these patients were not available to determine which patients had preexisting CKD and which patients developed CKD after surgery. Without such data, the proposed pathway by which the type of surgery influences the risk of CKD and subsequently the risk of CV events and mortality can be inferred but not directly observed.
Despite these limitations, our results have important ramifications for the treatment of small RTs. It is becoming increasingly evident that goals of treatment for RTs, particularly small incidental RTs, extend well beyond tumor control. Surgeons must carefully consider each patient on an individual basis and understand not only the biology of the disease but also the consequences that the treatment may have on the survivorship of the patient. Given the potentially serious, detrimental long-term effects of RN, it is worth reassessing the current treatment standards for RTs, making PN the preferred treatment for many newly diagnosed small tumors.