This article is more than 5 years old. Information may no longer be current.
Extended active surveillance feasible for some patients with metastatic kidney cancer
Select patients with advanced renal cell carcinoma may safely undergo active surveillance and delay aggressive systemic therapy, according to prospective phase 2 study results.
Treatment options for advanced kidney cancer are frequently noncurative and carry a substantial toxicity burden. It has been suggested that some patients with indolent metastases can initially undergo active surveillance.
“There is a perception that all cancers should be treated immediately because they are equally lethal,” Brian I. Rini, MD, FACP, professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, as well as a HemOnc Today Editorial Board member, said in a press release. “But what we’ve seen in this small phase 2 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.”
Brian I. Rini
Rini and colleagues evaluated data from 52 patients with treatment-naive, asymptomatic metastatic renal cell carcinoma. Patients received a baseline CT scan of the chest, abdomen and pelvis. Scans were repeated every 3 months during the first year of study, every 4 months during the second year, and every 6 months thereafter.
Active surveillance continued until the initiation of systemic therapy, which was decided mutually by the patient and treating physician. Patients did not have to discontinue active surveillance due to disease progression.
Time from the beginning of active surveillance to the initiation of systemic therapy served as the study’s primary outcome measure. Secondary outcome measures included changes to tumor burden from baseline and quality of life.
Median follow-up was 38.1 months (interquartile range, 29.4-48.9).
Four patients were removed from the study protocol due to withdrawal of consent (n = 3) or ineligibility (n = 1).
The per-protocol analysis included data from 48 patients (median age, 67 years; range, 62-75; 75% men) who had a median of 14.9 months (95% CI, 10.6-25) on active surveillance.
Forty-three patients (90%) had confirmed disease progression by RECIST criteria, of whom 37 initiated treatments.
The median time to progression was 9.4 months (95% CI, 7.4-13.4). Twenty-three patients (53%) immediately initiated systemic therapy upon confirmation of progressive disease; the remaining 20 patients (47%) continued on active surveillance, with a median additional surveillance time of 15.8 months (95% CI, 3-24.1).
Fourteen patients who initially remained on active surveillance initiated treatment at the time of reporting, and six patients have remained on active surveillance.
Three of the remaining five patients showed no disease progression. The other two patients left the study due to withdrawal of consent (n = 1) or loss to follow-up (n = 1).
Twenty-two patients (46%) died of their disease. Forty-one percent (95% CI, 27-55) of patients achieved 12-month PFS. This rate fell to 22% (95% CI, 11-34) at 18 months and 11% (95% CI, 3-24) at 36 months.
The cohort’s estimated median OS was 44.5 months (95% CI, 37.6-not reached).
The mean absolute change to tumor burden during the active surveillance period was 1.3 cm (95% CI, 0.6-1.8).
A multivariate analysis showed an association between a shorter surveillance period and a greater number of International Metastatic Database Consortium adverse risk factors (P = .0403), as well as a greater number of metastatic disease sites (P = .0414).
At baseline, seven patients (16%) had Hospital Anxiety and Depression Scale scores suggestive of anxiety and two patients (5%) had scores suggestive of depression. These scores did not significantly change during the active surveillance period.
The researchers acknowledged study limitations, including a highly selected study population that may not be representative of the general population with this disease, and the decision not to mandate systemic therapy initiation after confirmed disease progression.
“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,” Rini said.
A one-size-fits-all approach to active surveillance will likely not be possible for patients with advanced renal cell carcinoma, Paul Russo, MD, FACS, urologic oncological surgeon at Memorial Sloan Kettering Cancer Center, wrote in a related editorial.
“In this study, the effect of the aforementioned risk factors, coupled with the number of organs involved with metastatic renal cell carcinoma, effectively segregated the patients into disparate groups whose surveillance time differed by nearly three-times,” Russo wrote. “For the practicing oncologist, balancing the patient’s anxiety about having a fatal systemic disease and the desire for active intervention with a delay in treatment-related toxicity, expense and inconvenience requires a calm presentation of data such as these.”
However, appropriately selected patients are likely to benefit from watch-and-wait strategies, according to Russo.
“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,” Russo continued. “There is no evidence from this study that such a period of close surveillance jeopardizes the patient’s safety or survival.” – by Cameron Kelsall
Disclosure: One study researcher reports grants from GlaxoSmithKline and Pfizer outside the submitted work. Rini, the other researchers and Russo report no relevant financial disclosures.