Kidney Cancer Treatment Paradigm Is Challenged

ANN ARBOR, Mich., Sept. 19 -- Despite better detection and more curative surgery, kidney cancer mortality rates continue to rise, researchers here say.

This "treatment disconnect" means physicians should question the current paradigm of prompt surgery to remove all renal masses, according to Brent Hollenbeck, M.D., of the University of Michigan, and colleagues.

"These data do not encourage an abrupt departure from the current treatment paradigm for kidney cancer, Dr. Hollenbeck and colleagues wrote in the Sept. 20 issue of the Journal of the National Cancer Institute. "Rather, they prompt reflection on our clinical practice and suggest the need for investigation to address the observed 'treatment disconnect' that we are treating more and more small renal masses but are not impacting mortality."

The anomaly is seen in data from 1983 to 2002, the researchers noted, in which the rate of kidney cancer - driven mainly by masses 4 cm or smaller - rose sharply, paralleled by an increase in surgery for these smaller renal masses.

But over the same time, kidney cancer mortality rose, mainly owing to deaths among patients whose tumor mass at diagnosis was greater than 7 cm, the researchers said.

The researchers used patient data from nine registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program to assemble a cohort of 34,503 kidney cancer patients for whom tumor size at diagnosis was available. Another 6,310 patients were excluded because their records did not include tumor size.

The patients were divided into four groups on the basis of tumor size -- smaller than 2 cm, 2 to 4 cm, 4 cm through 7 cm, and greater than 7 cm. Overall, patients whose data was excluded tended to resemble patients whose tumor was greater than 7 cm, the researchers reported.

The study found that overall the rate of kidney cancer increased 52% -- from 7.1 to 10.8 cases per 100,000 population.

But most of the increase was driven by the detection of smaller masses. Specifically:

• For tumors less than 2 cm in size, the incidence went from 0.2 to 0.8 cases per 100,000 population.
• For tumors from 2 cm to 4 cm, the rate rose from 1.0 to 3.3 cases per 100,000.
• For tumors greater than 4 through 7 cm, the rate rose from 2.0 to 3.0.
• And for tumors greater than 7 cm, it rose from 2.3 to 2.9.

For the two smaller groups, the relative increase was 285% and 244%, respectively.

For each tumor size the increased rate of surgery was nearly identical to the increased rate of cancer, the researchers found.

Over the same time, the researchers found, the rate of cancer-specific deaths and all-cause mortality in the cohort also rose - from 1.2 to 3.2 and from 1.5 to 6.5 deaths per 100,000 population, representing a 155% and 323% increase, respectively. The rise in mortality occurred in all tumor classes.

"Despite more frequent surgical treatment for kidney cancers characterized by small tumors, mortality among patients with renal cell carcinoma has continued to increase," Dr. Hollenbeck and colleagues reported.

Part of the discrepancy can be attributed to length and lead-time biases, which can "produce an apparent improvement in patient outcomes, even if the intervention confers little or no mortality benefit," the researchers said. But the key factor is that the absolute number of large masses had not diminished.

"It is these larger, lethal masses that mainly mediate mortality," the researchers said.

When all the data is taken together, Dr. Hollenbeck and colleagues said, they "would suggest that these smaller cancers, or at least a proportion of them, represent an indolent form of renal cell carcinoma that may not merit surgical removal."

The study is limited by the fact that SEER databases do not collect information on co-morbidities, the researchers said, and it may also be affected by the exclusion of 15% of the kidney cancer patients, for whom no tumor size data were available. However, since those patients tended to resemble demographically the patients whose tumor masses were greater than seven centimeters, the exclusion may have tended to create an underestimate of mortality in that group.