Active Surveillance for Metastatic Cancer? Just This One

Nick Mulcahy

February 23, 2017

ORLANDO, Florida ― Active surveillance (AS) is a "feasible" option for the management of patients with metastatic renal cell carcinoma (mRCC) who have favorable- and intermediate-risk prognoses, according to a new single-center, retrospective study presented here at the Genitourinary Cancers Symposium (GUCS) 2017.

"In selected patients, active surveillance allows the delay of the start of systemic treatment," said lead study author David Bimbatti, MD, of the University of Verona in Italy.

"Active surveillance remains a reasonable approach for highly selected patients," added Primo "Lucky" Lara, MD, of the University of California, Davis, who acted as discussant of the presentation.

AS is not used in any other types of metastatic cancer, Dr Lara told Medscape Medical News.

The main caveats about the strategy are that "optimal patient criteria are not yet defined, and discontinuation criteria are not yet fully established," he told the meeting audience.

Nonetheless, other observers have pointed out that the strategy of waiting to start systemic therapy makes sense because mRCC has a highly variable course and a subset of patients have indolent or slow-growing disease. Additionally, the mainstays of treatment, tyrosine kinase inhibitors, are toxic, not curative, and need to be taken on a long-term basis.

The new study examined various clinical features of mRCC and related them to outcomes among the AS patients.

Discussant Dr Lara said the new study "reassuringly" indicated that "very few patients on active surveillance evolved into a worse prognostic group." This was a reference to the fact that only 4 of the 48 study patients, who started AS at the University of Verona sometime between 2007 to 2016, experienced a worsening of their International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) class while being monitored.

Before the start of AS, 69% of patients had a favorable prognosis/IMDC class assessment, 25% had an intermediate class assessment, and 6% had a poor class designation. All four of the patients for whom there was a drop in prognostic class were reclassified from the favorable to the intermediate group.

At baseline, most of the metastases were in the lung (56%) or the lymph nodes (23%).

During the study period, which has a median follow-up of 38 months, 37 patients stopped surveillance (71%), and 17 (33%) died.

The median time on surveillance of 19.9 months, which Dr Lara called "encouraging." This amount of time on surveillance was similar to other AS reports in this setting (14.9 to 18.7 months), he said.

The median overall survival of the study group was 77.6 months, which is "the highest ever overall survival for an active surveillance subset," Dr Lara highlighted.

The highest ever overall survival for an active surveillance subset. Dr Primo Lara

One of the clinical features that the study investigators assessed with respect to outcomes was tumor burden (defined as the number of sites of disease and the size of tumors).

All of the 48 patients experienced some increase in metastatic tumor burden.

However, only a change in tumor burden that was above the study group's median (ie, 2.2 times the original burden) was related to a worsening of postsurveillance survival, with a 23% increased risk for death once a patient surpassed the critical burden (hazard ratio [HR] = 1.23; P < .01).

That finding was qualified because a change in tumor burden above the median was not associated with poorer overall survival (HR = 1.0; P > .05) from baseline.

In other words, only postsurveillance survival, not overall survival, was poorer among patients in the study group who experienced a significant increase in their tumor burden.

As noted above, tumor burden was a combined measure of the number of sites of disease and the size of tumors.

Dr Bambatti and colleagues assessed the number of tumor sites, as well as any change in number, to see whether these factors had a bearing on outcomes.

He reported that, at baseline, metastatic tumor spread consisted of one site in 61% of patients, two sites in 35%, and more than two sites in 4%. During AS, the number of sites changed to one site in 35%, two in 48%, and more than two in 17%.

The investigators found that any increase in metastatic sites was associated with significantly worse postsurveillance and overall survival (HR = 2.6, P = .04; and HR = 3.3, P < .01) "Those hazard ratios are really high," commented Dr Lara during his discussion of the presentation.

Much to Be Learned

The optimal strategy for monitoring mRCC remains undefined, Dr Lara reminded the audience.

"Level one evidence for this is really lacking," he said, referring to prospective trials. "So we rely on expert opinion" that is based on retrospective data such as those presented in the new study.

However, Dr Lara highlighted the fact that the only prospective AS study of mRCC also concluded that select patients can safely undergo AS (Lancet Oncol. 2016:17:1317-1324), as reported by Medscape Medical News.

Dr Lara also said that the period in which to experiment with AS (before transitioning to active treatment) is "highly variable" in this setting. AS has been associated with a median overall survival of 2.5 to 5 years.

The new study provides new "tidbits of information to help us inform clinical decision making for patients with relatively indolent tumor biology," observed Dr Lara.

A limitation of the study is that it does not reflect psychosocial issues associated with AS, most notably anxiety.

"Critical questions" remain unanswered about AS, he said, and cited a few of them.

What are the validated selection criteria for AS? What is threshold for taking patients off AS? Is it 2.2 times the initial tumor burden? he asked, referring to the current study's findings.

Finally, what is the impact of metastastectomy? "Does it set back the clock if you cut out one of those metastatic sites?" he wondered.

For now, said Dr Lara, clinical practice must rely on "guesstimates" by experienced clinicians in terms of withholding treatment and monitoring patients actively.

Dr Bimbatti has disclosed no relevant financial relationships. Dr Lara has financial ties to multiple pharmaceutical companies.

Genitourinary Cancers Symposium (GUCS) 2017. Abstract 435, presented February 18, 2017.

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