Overall Cancer Risk Not Increased in ANCA Glomerulonephritis Patients, Study Suggests

Patients with ANCA-associated glomerulonephritis receiving immunosuppressive therapy are not more likely to develop cancer than the general population, a study found.

However, researchers did find that the risk for blood, post-transplant, and nonmelanoma skin cancers (NMSC) is higher among these patients.

Findings were reported in the study, “Cancer in ANCA-Associated Glomerulonephritis: A Registry-Based Cohort Study,” published in the International Journal of Nephrology.

The introduction of immunosuppressive therapy with cyclophosphamide in the 1960s considerably improved prognosis and survival in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

But studies thereafter began to suggest that cyclophosphamide treatment was associated with increased morbidity and risk of cancer.

Higher cancer incidence has been found in AAV patients treated with high cumulative doses of cyclophosphamide or when treatment lasted for more than a year, conditions that are rarely met during clinical practice.

There is also little information about the cancer risk in AAV patients treated with current immunosuppressive therapies such as azathioprine and Rituxan (rituximab).

To clarify this association, researchers in Norway quantified the risk of cancer in AAV patients with pauci-immune necrotizing glomerulonephritis, an ANCA-associated type of kidney disease.

The study included 419 patients registered in the Norwegian Kidney Biopsy Registry and diagnosed between 1988 and 2012, positive for ANCA, and followed for a mean of 7.2 years. Only patients who had cancer after the AAV diagnosis were included.

Researchers also joined data from four recent studies that included 1,532 patients with AAV diagnosed after 1988.

They found no difference in the overall incidence of cancer between AAV patients and the general population. But there was a significantly increased incidence, about three times higher, of nonmelanoma skin cancer and blood cancer in AAV patients.

Compared with the general population, patients that have undergone kidney transplants are also two times more likely to develop cancer.

Gender and ANCA type did not influence the overall cancer risk among patients.

Around 2003, azathioprine started to replace cyclophosphamide to reduce the cancer risk in patients with AAV, following international recommendations based on results from the CYCAZAREM clinical trial. Researchers in this current study found no difference in the risk of cancer in AAV patients either in the 1988–2002 or in the 2003–2012 periods.

Findings are in line with previous studies that have reported that an increased cancer risk was mainly due to higher rates of nonmelanoma skin cancer.

Although NMSC is not an inconsequential disease, deaths due to these tumors are low. Measures that can be taken to reduce the risks associated with NMSC include limiting sun exposure and careful monitoring.

Previous studies also have indicated that substituting cyclophosphamide for Rituxan may lower NMSC risk, although the decision to switch therapies must take into consideration effectiveness, treatment-related complications, and cost benefits.

Researchers argue that methodological differences may explain the conflicting findings between this and other studies that indicated an overall increased risk of cancer in patients on immunosuppressants, particularly cyclophosphamide.

Reasons for these discrepancies might be the exclusion of basal skin cell carcinomas, lack of registration in the database, and analysis of only the primary cancer in patients with several cancers. Other reports have also included subsequent cancer cases, particularly NMSC, in their incidence estimates. There is also no information about relapsing AAV, which might affect the risk of cancer because of its association with longer and higher doses of immunosuppressants.