Approximately two-thirds of kidney cancer tumors diagnosed in the United States are asymptomatic and small. Surgery remains the standard of care even though many of these tumors are likely to be indolent or even benign. Now, investigators have reported at the Genitourinary Cancers Symposium that surgical resection may compromise overall survival in older patients with small tumors, relative to surveillance (Abstract 343).
“I think this is an important observation and may help patients realize that a watchful waiting approach is a reasonable approach medically with lesions like this,” said Bruce Roth, MD, Professor of Medicine at Washington University School of Medicine in St. Louis, who moderated a news conference at which the data were discussed.
“This shows that not intervening not only won't have a negative impact, but that performing surgery on these individuals may have a negative impact because they will have an increased risk of cardiovascular events and, perhaps, cardiovascular mortality.”
To assess the impact of surgery and surveillance on overall survival, cancer-specific survival, and cardiovascular events, William C. Huang, MD, Associate Professor of Urology at NYU Langone Medical Center, and colleagues analyzed data from the Surveillance, Epidemiology and End Results (SEER) database and linked Medicare records. A total of 8,317 patients age 66 or older who were diagnosed with a 4 cm or smaller renal mass between 2000 and 2007 were identified. Of those, 7,148 patients had a pathological diagnosis of kidney cancer and formed the study group for the remaining analyses.
The majority of patients (78%) underwent surgery, two-thirds of which were radical nephrectomies. The remaining 1,584 patients (22%) underwent surveillance, which was defined as no surgery within the first six months after diagnosis. Just six percent of patients who were initially followed with surveillance later underwent surgery, and these patients were included in the surveillance group for the analyses.
The use of surveillance increased during the study period, starting at about 25 percent in 2000 and climbing to about 37 percent in 2007. However, when the investigators restricted their analysis to just those patients with a pathogic diagnosis of kidney cancer, the use of surveillance varied year to year, with the lowest rate of 17 percent in 2004 and the highest rate of 27 percent in 2006.
A total of 1,536 patients died in the study group as a whole. With a median follow-up of 64 months, 1,333 patients in the surgery group (24%) died, compared with 203 (13%) in the surveillance group with a median follow-up of 57 months.
The investigators found an association between initial treatment and risk of death, but the association varied over time. During the first six months after diagnosis, surveillance was associated with a 27 percent increased risk of death compared with surgery. However, between seven and 36 months after diagnosis, surveillance was associated with a 30 percent reduction in risk of death relative to surgery, which was statistically significant. Beyond 36 months, that benefit grew to a 63 percent reduction in risk in the surveillance group compared with the surgery group.
When the investigators divided the surgery group into patients who underwent radical nephrectomy and those who had a partial nephrectomy, it was evident that patients with kidney-sparing surgery had an intermediate risk of death in late follow-up, relative to radical nephrectomy and surveillance. However, for the first 60 months or so of follow-up, patients who had had a partial nephrectomy had longer survival than the surveillance group.
Remarkably, the team found, there was no difference in cancer-specific survival between the surveillance and surgery groups. Just three percent of the total population died of kidney cancer, including two percent of patients who underwent surveillance and three percent of patients who underwent surgery.
Cardiovascular Risk Higher with Surgery
There was, however, a big difference in the risk of cardiovascular events. Whereas 24 percent of the population as a whole had a cardiovascular event, the incidence was significantly different in the surgery group (27%) and the surveillance group (13%). In other words, surveillance was associated with a 49% reduction in risk of cardiovascular events relative to surgery, which was a statistically significant difference.
When asked about the link between cardiovascular problems and kidney surgery, Huang said that resecting a kidney puts a patient at higher risk for chronic kidney disease, which in turn increases the risk of cardiovascular disease. “To this day, the majority of small tumors are removed by radical nephrectomies,” he said. “We are doing a better job though, of recognizing the negative consequences of removing the whole kidney. At tertiary care centers, approximately 90 percent are partial nephrectomies for small tumors. But when you look at the U.S. population overall, over half of the small tumors are still being removed by removal of the whole kidney.”
The benefits of a partial nephrectomy can be seen in the new data, he said. “If you look at the survival lines that I showed, the differences in survival occurred much, much later in those who had a partial nephrectomy” compared with surveillance.
Cautious Approach Warranted
Huang was careful to emphasize that the study had important limitations. First and foremost, it is a retrospective study and, as such, the two treatment groups differed significantly in many ways, including age, geographic differences, baseline characteristics, and comorbid conditions.
“Also we need to keep in mind that this analysis was limited to patients 66 and older, so you cannot extrapolate to younger patients with kidney cancer,” he said.
Moreover, he continued, the small tumors are very heterogeneous. “We always need to keep in mind that a small but real number of tumors will metastasize and lead to death.” Distinguishing between dangerous lesions and benign ones remains a challenge, however. Additionally, the study provides no information on how one should follow patients who choose surveillance.
“Therefore, surgical excision remains the treatment of choice for patients with a normal life expectancy,” he concluded. “But surveillance appears to be a reasonable option for patients with a limited life expectancy.”
The meeting is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.