What tests and exams should be ordered to monitor for relapse of lymphoma in a patient in remission?

Monitoring Lymphoma in Remission

For patients with lymphoma in complete remission, surveillance should consist of history and physical examination every 3 months for the first 2 years, every 6 months for years 3-5, then annually, combined with complete blood count and LDH at 3,6,12, and 24 months—routine surveillance imaging with CT or PET is NOT recommended as it rarely detects relapse before symptoms appear and does not improve survival. 1, 2

Core Surveillance Strategy

Clinical Monitoring Schedule

First 2 years (highest risk period):

• History and physical examination every 3-4 months 1, 2
• Complete blood count at 3,6,12, and 24 months 1, 2
• LDH measurement at same intervals 2

Years 3-5:

• History and physical examination every 6 months 1, 2
• Blood work only as clinically indicated 1

Beyond 5 years:

• Annual history and physical examination 1, 2
• Attention to secondary malignancies and late treatment effects 1, 2

What to Assess at Each Visit

History should specifically evaluate for:

• Constitutional B symptoms (fever, night sweats, weight loss >10%) 2
• New or enlarging lymphadenopathy 3
• Fatigue or performance status decline 2
• Organ-specific symptoms suggesting extranodal involvement 3

Physical examination must include:

• All lymphoid regions (cervical, supraclavicular, axillary, inguinal) 2
• Abdominal examination for hepatosplenomegaly 2
• Documentation of performance status 2

The Evidence Against Routine Imaging

Routine surveillance CT or PET scans are explicitly NOT recommended because multiple studies demonstrate they are ineffective and costly 1, 3, 4, 5:

• Only 17-27% of relapses are detected by routine imaging 3, 4
• 64-78% of relapses are detected by patient-reported symptoms or physical examination 3, 4, 5
• Imaging-detected relapses show no survival advantage in most studies 6, 5
• The estimated number of scans needed per relapse detected ranges from 91-255 4
• Surveillance imaging accounts for >75% of follow-up healthcare costs 5

Limited Imaging Indications

CT imaging may be considered only in specific circumstances:

• Hodgkin lymphoma patients: CT every 6 months for 2 years, then annually up to 5 years (older guideline recommendation) 1
• When clinical findings are equivocal and would change management 1
• High-risk patients with curative salvage options available 1

PET surveillance is explicitly discouraged:

• Not recommended for routine follow-up in DLBCL 1
• No consensus on utility in Hodgkin lymphoma due to false positives from fibrosis 1
• Not recommended in follicular lymphoma 1

Treatment-Specific Monitoring

For Patients Who Received Radiation Therapy

Neck irradiation:

• Thyroid function testing (TSH, FT3, FT4) at 1,2, and 5 years minimum 1, 2

Chest/mediastinal radiation:

• Annual breast cancer screening for women >35 years who received radiation above the diaphragm 1, 2
• Cardiovascular monitoring for all patients 1

For Patients Who Received Anthracyclines

• Cardiovascular monitoring is recommended 1
• Echocardiography or MUGA scan if further anthracyclines are being considered 1

When Relapse is Suspected

Biopsy is mandatory before initiating salvage therapy 1:

• Early relapse (<12 months) of well-established histology may not require repeat biopsy unless excluding second malignancy 1
• Late relapse (>12 months) requires histological verification to exclude transformation (e.g., follicular to DLBCL) 1
• Core needle biopsy is acceptable when excisional biopsy is not feasible 1

Full restaging workup includes:

• CT chest/abdomen/pelvis or PET/CT 1
• Complete blood count and comprehensive metabolic panel 1
• LDH and uric acid 1
• Bone marrow biopsy in selected cases 1

Critical Pitfalls to Avoid

Do not order routine surveillance imaging in asymptomatic patients—this is the most common and costly error, with no survival benefit and potential for false positives leading to unnecessary procedures 1, 3, 4, 5

Do not ignore patient-reported symptoms between scheduled visits—these detect the majority of relapses and should prompt immediate evaluation 3, 4, 5

Do not skip long-term monitoring beyond 5 years—focus shifts to secondary malignancies and late treatment effects rather than lymphoma relapse 1, 2

Do not forget treatment-specific surveillance for thyroid dysfunction, cardiac toxicity, and secondary breast cancer in appropriate populations 1, 2