Surveillance of Sarcoma

Thoughts and upcoming research

Obligatory—This is not medical advice

We’ve talked about before how the treatment recommendations for sarcoma are typically fairly controversial. Part of the genesis of this is that there are so many different diagnoses, and, for that reason, the precision of our clinical trials has been mixed. This is why it’s so important that us physicians are open and honest about what we do and don’t know.

A large proportion of patients seen in our clinics have already had curative intention surgeries performed for their disease—possibly with radiation, chemotherapy, or a combination. They’ve gotten through treatment and are now in the middle of a process we call surveillance. Surveillance is when a patient does not have visible disease and is being followed to see if their cancer returns. Throughout surveillance we perform imaging and assess for symptoms. The best analogy I have is this is a primary care checkup specifically devoted to their cancer and life after cancer therapy. For patients with head and neck sarcomas who got radiation, we may be helping with xerostomia (dry mouth). For patients with exposure to chemotherapy, we could referring them seeing an audiologist for tinnitus, or a cardiologist if there are problems with the heart. Surveillance guidelines depend heavily on the particular aspects of the diagnosis and are usually made through a process that we call expert consensus. Expert consensus is when a group of doctors who are experienced in treating a condition review the data that is available and determine what the standards should be. The most heavily referenced here within the United States is the NCCN, whose sarcoma recommendations are here (see footnote).¹  

The problem is, like with other forms of recommendations for healthy populations of people, it’s been very hard to make firm statements about doing CT scans or MRIs. There are often hidden costs that go unrecognized—both financially and otherwise. Furthermore, there is a lack of data that this necessarily helps our patients live longer, and cumulative effects of radiation from CT or other radiation-based scans may have future harms that we haven’t quantified yet. For that reason, it’s really important that we study surveillance further.  

Would patients participate in surveillance trials?

To see if pursuing this question was acceptable for patients with sarcoma, a survey conducted at academic medical centers was conducted and published in 2021.² Trials have also begun enrolling, too.³  

The survey above was performed at academic medical centers in Canada, Europe, and the United States. Patients invited must be at least 18 years of age, be able to write and read English, French, or Spanish, and have recently completed treatment for extremity soft tissue sarcoma (sarcoma confined to the limb). Questions were vetted by experts in oncologic care, and health research. In total there were 58 questions (pretty lengthy) which used scales, multiple choice, and open ended responses.  

92% of patients approached completed the survey. Mean age was 56 years, 60% were male, 82.3% were white and the majority of the patients were from Canada and the USA (6.9% from Spain). See table 1 below 

Schneider et al. BMJ Open. 2021. (Reference #2)

This reflects a somewhat skewed population of patients in a way from a racial and socioeconomic status standpoint. While I cannot comment on Canada and Spain, I would say that our demographics are somewhat different from that listed here. We generally take care of patients with a lower household income and with higher representation of non-white ethnicities. This may limit the ability to extrapolate from this survey to the patients at our center. 

Understanding those, and the significant limitations with the methods, these data are nonetheless interesting when it comes to determining how patients perceive research on surveillance. It also shows how important it is that we’re transparent with our studies and results. Table 4 here shows that most patients are willing to participate in research in general but are more hesitant about the process of randomization. It is probably worthwhile for physicians to make sure that this is explained well, and that the concept of equipoise—that is theoretical equivalence between arms of a trial—is part of that explanation.  

Schneider et al. BMJ Open. 2021 (Reference #2)

The results of this survey seem to indicate, that within the cross section asked, patients would be very willing to participate in research in sarcoma. The reasons as to why are probably beyond the scope of this post, but I imagine that it’s because of the good will that they feel towards the medical team, in particular the doctors who deliver this care. The backbone of this is all is trust. They trust us to make the best decisions, to answer the right questions, and to give the right treatment.

This survey seems to justify proceeding with a pilot trial for surveillance in this population, the ‘Surveillance After Extremity Tumor surgerY ‘ (SAFETY) trial, whose protocol is here.

The idea behind the SAFETY is to better define how often and by what method (CT or chest x-ray) we should be performing imaging on our patients with high grade extremity soft tissue sarcoma. There are two questions being asked and therefore four cohorts (see flow chart below).

Questions:

1. Is CT superior to Chest x-ray?

2. Is an interval between scans of 3 months superior to 6 months?

The primary outcome of this study is eventually going to be is overall survival. The proposed superiority threshold is 10% overall survival benefit at 5 years. This had been established as clinically meaningful by the American Society of Clinical Oncology. ⁴ This is the appropriate endpoint for patients—and ultimately what they want to know: does scanning me more often actually help me live longer, or does it simply expose me to excess radiation and anxiety?

SAFETY Trial Protocol

I’m very impressed by this trial. It’s parsimonious and very academic. While there remain open questions regarding feasibility (hence why it’s been organized this way), it is fairly rigorous.

For the foreseeable future, however, for most of our patients, we will be relying on expert consensus as mediated by the NCCN and other guidelines. This should all be done in concert with patient preference, as while experts have deemed what’s acceptable, the individual’s voice should ring through in situations where data is uncertain.

1. https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf

2. https://bmjopen.bmj.com/content/bmjopen/11/2/e042742.full.pdf

3. https://clinicaltrials.gov/ct2/show/NCT03944798

4. https://pubmed.ncbi.nlm.nih.gov/24638016/