Early Stage FL: Best Treatment?

I don't write a lot about early stage Follicular Lymphoma -- stage 1 or 2. Honestly, it's partly because I was diagnosed at stage 3, and later stage stuff catches my eye more.

But in reality, there isn't much written about it. Most of us (at least 75%, probably more) are diagnosed with stage 3 or 4 FL. It's just harder to catch when it's early. And so later stage FL gets much more of the research attention.

The Journal of Clinical Oncology just published some of that less-common research, in an article called "Randomized Trial of Systemic Therapy After Involved-Field Radiotherapy in Patients With Early-Stage Follicular Lymphoma: TROG 99.03."

One of the potentially positive things about stage 1 or 2 FL is that it might be curable. For about 50% of patients, localized radiation treatments in affected nodes can result in a cure. That doesn't work with later stage FL (and obviously doesn't work with everyone with early stage, either).  For most of us, that kind of focused radiation doesn't work, since cancer cells are moving all around our blood stream. (We have RadioImmunoTherapy, though. Same idea, but for a moving target.)

The JOC article describes a long-term study (it took place from 2002 to 2012) in which early stage FL patients were given either radiation of their affected nodes, or radiation plus the chemotherapy combination CVP (and after 2006, CVP + Rituxan). There were 75 patients in each group. The results: the Progression-Free Survival (PFS) over 10 years was 41% for just radiation, and 59% for radiation + immunochemotherapy. (Overall Survival, however, was not significantly different.)

It's an interesting study, but one that has some flaws. For one thing, it's fairly small (150 patients). It also changed, with the addition of Rituxan after 4 years (making the full comparison harder). The amount of radiation recommended in 2002 was higher than it is now. And PET scans were recommended, but not required, for participants (it's pretty much standard now to use PET scans as a way of measuring results in a study like this).

(All of those flaws, by the way, were pointed out in a commentary about the study, published in the same issue of JOC. Just so you don't think I came up with that stuff myself...)

So it's not a perfect study, but it does teach us some things. And as the writers of the commentary point out, it raises some interesting questions:

• A lot of the increase in PFS came after 2006, when Rituxan was added to the chemo. Would radiation + Rituxan do the job, leaving out chemo altogether?
• Would other non-chemo options also work? Maybe R-squared (Rituxan + Lenalidomide)?
• Would those options be less expensive? Should cost also be measured in a follow-up trial? [My answer is Yes -- it should be measured in every trial.]
• Given that, even with just the radiation, 41% of patients had a 10 year PFS, should early stage FL patients not be put on watch and wait? Is it better to treat immediately and take a chance of a cure?

Part of the problem with this study is that there are relatively few stage 1 and 2 FL patients, so there were fewer people to recruit for the trial. That's why it took 10 years to complete -- it took that long to recruit patients. And with a trail that long, you have some of the problems that came out -- practices change over time.

So, if you are a stage 1 or 2 Follicular Lymphoma patient, especially one who is newly diagnosed, I think the big lesson here is that there are some things to talk about with your doctor. Radiation could be an option, as could radiation + something, whatever that might be. Treatment options might not be as simple as they seem.

The other lesson -- if you are early stage, consider doing a clinical trial. More good stuff like this can only come if people volunteer.

I'm glad I got the rare chance to write about stage 1 and 2 FL research. I hope there's more to come.