Active Surveillance May Be Possible for Some With Metastatic RCC

Certain patients with metastatic renal cell carcinoma (RCC) safely underwent active surveillance of their disease prior to undergoing systemic therapy in a phase II study published in Lancet Oncology.

In the study, participants had a median surveillance period of 1 year or longer before starting active therapy, and no adverse effects on quality of life, anxiety, or depression were observed.

“There is a perception that all cancers should be treated immediately because they are equally lethal. But what we’ve seen in this small phase II study is that a subset of adults with advanced kidney cancer have slow-growing disease that can be safely managed using active surveillance, which could spare them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some cases several years, without worsening anxiety and depression,” said lead author Brian Rini, MD, of Cleveland Clinic’s Taussig Cancer Institute, in a prepared statement. “With just 50 people involved in our trial, the risk and benefits of the approach will need to be studied in a larger group of patients.”

According to the study, there is a subset of patients with metastatic RCC that have indolent growth of metastases. About one-third of patients who undergo surgery to remove their disease remain disease free at 5 years; however, little is known about the use of active surveillance as an initial treatment strategy.

In this prospective study, Rini and colleagues enrolled 52 patients with treatment-naive, asymptomatic, metastatic RCC. Patients were assessed at baseline, every 3 months for year 1, every 4 months for year 2, and then every 6 months. Patients were observed until they and their physician made the decision to begin systemic therapy for their disease.

Forty-eight patients were included in the analysis, which had a median follow-up of 38.1 months. The median time of active surveillance was 14.9 months, and overall survival from the start of surveillance was 44.5 months.

The majority of patients (90%) had disease progression during the study; 37 patients started systemic therapy. However, about one-half of patients chose to continue on surveillance for an average of 15.8 additional months after disease progression. A multivariate analysis showed that patients with more International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) adverse risk factors (P = .0403) and a higher number of metastatic disease sites (P = .0414) were under surveillance for a shorter period of time.

“On the basis of this analysis, we identified two prognostic groups through use of a recursive partitioning algorithm-a favorable group consisting of patients with no or one IMDC risk factors and two or fewer organs with metastatic disease, and an unfavorable group consisting of all other patients,” the researchers wrote. “The favorable group comprised 29 (60%) patients and had an estimated median surveillance time of 22.2 months (95% CI, 13.8–33.3), whereas the 19 (40%) patients in the unfavorable group had an estimated median surveillance time of 8.4 months (95% CI, 3.2–14.1; P = .0056).”

When assessed at baseline, 16% of patients had surveillance scores that suggested anxiety and 5% had scores suggestive of depression. These scores did not significantly change while patients were under surveillance. Additionally, there were no significant changes in quality-of-life scores during the surveillance period. Although 22 patients died during the study, only one patient died without ever having started systemic therapy.

The researchers noted that the patients in this study were highly selected and the decision to end surveillance and begin systemic therapy was not defined by the study but left up to the treating physician; therefore, “these study features limit the applicability of this approach.”

In an editorial published with the study, Paul Russo, MD, of Memorial Sloan Kettering Cancer Center, wrote, “This paper provides guidance to both medical and surgical oncologists who, when faced with a newly diagnosed patient with metastatic renal cell carcinoma who has good performance status and limited metastatic disease, can offer a period of close surveillance with the potential for prolonged survival before disease progression and the initiation of systemic therapies. There is no evidence from this study that such a period of close surveillance jeopardizes the patient’s safety or survival. It remains to be seen whether current genomic research can identify genes that can be used in conjunction with the above described selection factors to better choose patients suitable for initial active surveillance.”