Watch & Wait in Follicular Lymphoma

Follicular lymphoma is indolent (slow-growing), and (at least for the moment) incurable. For this reason, studies have shown in the past that there is no benefit to beginning immediate treatment per se. The exception is in early, localized disease, when chemotherapy and radiation treatment may be able to effect a cure. Most patients have advanced (Stage III or Stage IV) disease at diagnosis, but have no symptoms (are "asymptomatic") other than swollen lymph nodes.

That doesn't mean "watch & wait" is a comforting strategy for patients, though. Quite the contrary -- "watch & worry," as the less formal title for this strategy goes, can be a time of great stress and anxiety. For this reason, it's important to know the arguments for and against watch and wait, to determine whether this really is beneficial for you and your loved one.

How Watch & Wait (W&W) Works

Nervous patients understandably put the emphasis on the "wait" part. Oncologists tend to put the emphasis on the "watch" part. During watch and wait, patients check in with their physician on an established schedule, such as every three tests. Palpable (feelable) lymph nodes are examined, blood counts are taken, and standard scans (such as CT scans) are ordered, and the results are compared with those of the previous examination. For most patients, follicular lymphoma grows slowly, and these checkups allow the doctor and patient to monitor the progress of the disease. Eventually, usually when symptoms appear (criteria are discussed in further detail below), watch and wait ends and treatment begins.


When Watch & Wait Ends

The standard doctrine, which can be found (for instance) in the protocols of the BC Cancer Agency, is not to treat until a person is "symptomatic" -- meaning that, in addition to swollen lymph nodes, they also have one or more "B" symptoms:

• Weight Loss (10+% body of weight in six months or less)
• Drenching Night Sweats
• Fever

There are, however, a number of other situations in which further progression is associated with worse prognosis, and therefore oncologists may recommend that treatment begin immediately. The Adult Lymphoma Study Group (GELA), which was responsible for the major PRIMA study of rituximab maintenance, listed the following as indications of the need for treatment:

• Bulky Disease (one lymph node greater than 7 cm long, or three lymph nodes longer than 3 cm each)
• Elevated LDH and/or beta-microglobulin levels
• Enlarged Spleen
• Pleural Effusion
• Compressive Syndrome (compression of the heart or important blood vessels by tumours)

Finally, bear in mind that the purpose of watching and waiting is to prolong normal quality of life as long as possible before beginning chemotherapy. If anxiety is severe enough to ruin that quality of life anyways, there may be little reason to continue waiting.

How long the watch and wait period lasts depends on the severity and aggressiveness of the disease. Some people require treatment within months of being diagnosed, while some others experience a deacde of relatively stable disease. In 1979, a study estimated that half of patients began treatment within about 2.5 years.

Why to "Watch and Wait"

There are two basic arguments behind watch and wait. First, a number of pivotal early studies showed that chemotherapy could shrink tumours but had little impact on overall survival times: that is, it would be more or less as effective (or ineffective) whether started early or late in the course of the disease. The same 1979 study compared 112 patients who were treated immediately with 44 who were put on "watch and wait" for up to several years' time. After four years, 77% of the "watch and wait" patients were still alive, compared with 83% of the immediate-treatment people.

The impact of the monoclonal antibody era on these statistics is still debated. Some oncologists feel that rituximab, and particular Zevalin, have the potential to induce long, deep complete remissions, and, if so, that these may be more easily induced immediately, before the disease is allowed to progress any further. Others argue that while rituximab-based regimens have certainly improved survival rates, the conventional wisdom (that early and late treatments are equally effective) still holds true.

The second argument is that watching and waiting allows the patient to -- potentially -- take advantage of new drugs just now entering clinical trials. The treatment picture for follicular lymphoma has changed substantially since the introduction of the rituximab anti-CD20 monoclonal antibody a little over a decade ago. Zevalin and Bexxar are also very impressive.

It is this argument which now seems most persuasive. A number of exciting new drugs are on the clinical horizon, including new anti-CD20 antibodies (like GA-101 and ofatumumab), anti-CD22 antibodies (e.g. ofatumumab ozogamicin and epratuzumab), and, most importantly, advanced inhibitors like CAL-101. A patient who waits, for instance, three years before beginning treatment may actually find that the drugs of choice have changed and become more effective in the meantime. This might be worth the wait.

When Watch & Wait Doesn't Work

There are some patients, however, for whom watch & wait is not a good option. First, some patients will present with criteria that already indicate a need for treatment, such as B symptoms.

More importantly, there is good evidence that aggressive immediate treatment, including radiation, for the small minority of patients who present with early localized (Stage I or non-bulky Stage II) disease can actually cure the disease. This is worth taking advantage of, since follicular lymphoma is still considered incurable in its advanced stages. Long-term results from an Australian-American study of 102 early-stage patients found a complete remission rate of 99% after CHOP-Bleomycin, and a 10-year survival rate of 80%, with 72% still free of new disease progression at that milestone. Current rituximab-based regimens probably improve further on these statistics.