Treatment of Stages I - II Follicular Lymphoma
Medically reviewed by Dr. C.H. Weaver M.D. (08/2018)
Patients with stage I or II follicular Non-Hodgkin lymphomas have limited disease; limited disease is potentially curable.
Some stage II disease is more advanced and is referred to as stage IIE. These patients have large tumors or extranodal “E” disease and have a much greater risk of cancer progression after treatment. This is discussed under Stage IIE-IV Follicular Non-Hodgkin Lymphoma.
Follicular lymphoma is a slow growing cancer, which means that patients may survive for a long time without treatment. The major dilemmas regarding treatment of follicular lymphomas are when to initiate treatment and whether more aggressive treatments can improve a patient’s outcome compared to treatment with radiation therapy alone.
About this Lymphoma Treatment Information
The following is a general overview of treatment for stage I-II follicular lymphoma. Cancer treatment may consist of radiation therapy, chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques has become an important approach for increasing a patient’s chance of cure and prolonging survival.
In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Treatments that may be available through clinical trials are discussed in the section titled Strategies to Improve Treatment .
Circumstances unique to each patient’s situation influence which treatment or treatments are utilized. The potential benefits of combination treatment, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
Types of Follicular Lymphoma
Follicular lymphomas are classified according to two systems, the Revised European American Lymphoma (REAL) system and the International Working Formulation (IWF). The following are types of follicular Non-Hodgkin lymphoma (NHL); they are treated similarly (see table 1).
Table 1 Types of Follicular NHL according to two classification systems, REAL and IWF
When to Initiate Treatment
Many patients diagnosed with limited stage I-II follicular lymphomas remain asymptomatic and may not require treatment for several years. In fact, treatment may not be initiated until three to four years after diagnosis. Some patients may go without treatment for even longer.
However, follicular lymphoma may progress into advanced disease, which is less curable with currently available treatments. For this reason, some patients may choose to undergo early treatment that may cure their disease.
Treatment is typically initiated for one of the following reasons:
- To relieve symptoms caused by lymphoma that may include fever, sweating, or weight loss.
- To prevent the lymphoma from growing in an area where it affects other organ functions, such as the kidneys.
- To improve low blood counts that may be caused by cancer in the bone marrow.
- To treat steady growth or progression of lymphoma.
- Patient preferences: some patients feel uncomfortable living with lymphoma and would prefer to be treated even in the absence of the above reasons.
Radiation therapy is the traditional technique for treating stage I-II follicular lymphoma. However, results from small clinical trials suggest that more patients experience long-term survival if chemotherapy is administered. (Large clinical trials are necessary to confirm these observations.)
Radiation Therapy for Early Stage Follicular Lymphoma
Radiation therapy delivered early to patients with limited disease appears to cure up to 40% of patients. However, radiation therapy is not without risks—researchers have reported that 7%–17% of patients treated with radiation therapy develop a new cancer that may be attributable to receiving radiation therapy. 
Researchers have reported that radiation therapy can cure approximately one half of patients with stage I and one quarter of patients with stage II follicular lymphoma. These researchers reviewed outcomes of 33 patients with stage I disease and 47 patients with stage II disease treated with radiation therapy alone. Nearly nine out of 10 patients (87%) with stage I disease and more than half (54%) of patients with stage II disease survived 15 years or more after treatment. Patients with smaller tumors were more likely to experience long-term survival. 
Chemotherapy for Early Stage Follicular Lymphoma
Patients with stage I-II follicular lymphoma were treated with four cycles of combination chemotherapy. After chemotherapy, patients with residual disease were treated with radiation therapy. The outcomes appear to be superior to treatment with radiation therapy alone. Approximately 95% of patients experienced a complete anticancer response to treatment, and 95% survived five years or more. Seventy percent of patients were free from cancer relapse for five years or more. 
Radiation Therapy plus Chemotherapy for Early Stage Follicular Lymphoma
A clinical trial that treated all patients with chemotherapy plus radiation therapy indicated that long-term outcomes with this approach may be superior to radiation therapy alone. The researchers reported that eight out of 10 (80%) of patients with stage I-II follicular lymphoma treated with chemotherapy and radiation therapy survive 10 years or more. 
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of stage I-II follicular lymphoma will result from the continued evaluation of new treatments in clinical trials.
Patients may gain access to better treatments by participating in a clinical trial. Participation in a clinical trial also contributes to the cancer community’s understanding of optimal cancer care and may lead to better standard treatments. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of stage I-II follicular lymphoma include the following:
New combinations of chemotherapy: Development of new chemotherapy treatment regimens that incorporate new or additional anticancer therapies—including targeted therapies—is an area of active investigation. There has been significant progress in the development of targeted therapies and new treatment regimens for advanced follicular lymphoma. These may prove beneficial in the treatment of patients with stage I-II disease. For more information go to the targeted therapy sections in Stage IIE-IV Follicular Lymphoma.
 Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University . Journal of Clinical Oncology. 1996;14:1282-1290.
 Wilder RB, Jones D, Tucker SL, et al. Long-term results with radiotherapy for stage I-II follicular lymphomas. International Journal of Radiation Oncology Biology Physics. 2001;51:1219-1227.
 Lombardo M, Morabito F, Merli F, et al. Bleomycin, epidoxorubicin, cyclophosphamide, vincristine and prednisone (BACOP): results of a prospective, multicenter study of the Gruppo Lymphoma Per Lo Studio Dei Linfomi (GISL). Leukemia Lymphoma. 2002;43:1795-1801.
 Seymour JF, Pro B, Fuller LM, et al. Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent Non-Hodgkin lymphoma. Journal of Clinical Oncology. 2003;21:2115-2122.