The main treatment options for most of these patients are combination chemotherapy alone, or together with radiation therapy when there is a particularly large tumor. If patients have other serious health problems and would be unable to tolerate the side effects of chemotherapy, radiation therapy alone is a good option if the disease is truly localized. The usual chemotherapy combination for aggressive NHL is cyclophosphamide, doxorubicin hydrochoride, vincristine (Oncovin), and prednisone, commonly called CHOP. Several other chemotherapy combinations with more side effects such as BACOD, MACOP-B, and ProMACE-CytaBOM, have been tested and survival rates are similar to those obtained with CHOP chemotherapy. CHOP chemotherapy remains the standard for the present time. If the cancer does not respond completely to the chemotherapy or if it returns after a period of remission, more chemotherapy combinations, including different drugs are recommended. One of these combinations uses etoposide, vincristine, cyclophosphamide, and doxorubicin (abbreviated EPOCH). Five-year survival rates are in the range of 60% - 70%.

The 5-year survival rate refers to the percent of patients who live at least 5 years after their cancer is diagnosed. Many of these patients live much longer than 5 years after diagnosis, and 5-year rates are used to produce a standard way of discussing prognosis. Five-year relative survival rates exclude from the calculations patients dying of other diseases, and are considered to be a more accurate way to describe the prognosis for patients with a particular type and stage of cancer. Of course, 5-year survival rates are based on patients diagnosed and initially treated more than 5 years ago. Improvements in treatment often result in a more favorable outlook for recently diagnosed patients.