Imaging studies are required for the correct staging and treatment planning for rNPC. Computed tomography (CT) and MRI are recommended for the diagnostic evaluation of the extent of the cancer. MRI appears to be better than CT imaging for visualizing soft tissue invasion outside of the nasopharynx, demonstrating involved retropharyngeal nodes, and identifying skull base or intracranial involvement. MRI is also valuable in defining locally recurrent cancer. Both MRI and CT scans have a low sensitivity and moderate specificity for detecting rNPC and for distinguishing recurrence from postradiation changes. MRI is superior to CT in differentiating postradiation fibrosis from rNPC. Early recurrence is difficult to identify because immature scars and well-vascularized granulation tissues generally reveal contrast enhancement. Sophisticated nuclear medicine examination, such as positron emission tomography (PET) scans, appears promising for the detection of rNPC. Asymptomatic distant metastases are not rare at the initial presentation; thus, a pretherapeutic evaluation with positron emission tomography with [18F] fluoro-2-deoxy-d-glucose (FDG-PET) is recommended in the staging process. On PET scans, a viable tumor is seen as a focal area of increased FDG uptake due to its hypermetabolic activity, while radiation fibrosis is hypometabolic and appears as a focal area of decreased uptake. This technique may be superior to CT or MRI for detecting recurrent or residual disease. PET, however, cannot provide detailed anatomic information about the location of lesions, invasion of vascular and bony structures, and submucosal spread. Falsepositive results may also occur in PET because of hypermetabolic features seen in the inflammatory process.

Differentiating between locally recurrent cancer, radiation-induced necrosis, and scarring in the nasopharynx by direct visualization with endoscopy or radiologic imaging is difficult until the tumor mass becomes grossly visible with ulceration or asymmetric change in the mucosa. It has been reported that the appearance of the mucosa of the nasopharynx does not necessarily correlate well with the occurrence of early NPC. Epstein-Barr virus (EBV) is a double-stranded DNA virus, which is closely related to NPC. The presence of EBV in NPC is well documented. Almost every NPC tumor cell carries clonal EBV genomes and expresses EBV proteins such as latent membrane proteins. Quantification of plasma EBV DNA is useful for monitoring patients with NPC and predicting the outcome of treatment. The detection of EBV genomic latent membrane protein 1 (LMP-1) using a nasopharyngeal swab technique has a sensitivity of 81.8% and a specificity of 98.3% for predicting mucosal recurrence of NPC. A recurrence in the mucosa should be strongly suspected if LMP-1 is present again in patients with treated NPC who had a latent disease remission of LMP-1 that exceeded 6 months, even if a nasopharyngoscopy revealed no abnormality. In such situations, further investigation by punch biopsy or imaging, such as MRI or PET scans, needs to be considered.

Undoubtedly, detection of EBV LMP-1 by PCR assay with nasopharyngeal swabbing should be incorporated as an important part of a follow-up investigation in all NPC patients treated with radiotherapy. The detection of LMP-1 again in NPC patients treated with radiation can enhance physicians’ awareness and encourage physicians to shorten patient follow-up intervals, pay increased attention to changes in the nasopharynx, and even perform biopsies more frequently in suspicious areas of the mucosa in the nasopharynx. Thus, it is reasonable to expect that mucosal recurrence may be diagnosed earlier using detection of LMP-1 as one of the followup screening modalities. Moreover, salvage treatment can be more successful when rNPC is detected early.

The role of LMP-1 as a tumor marker to monitor local or residual cancer after RT has been established. In one report, of the 12 patients with local recurrence, 11 patients had positive LMP-1, including 2 cases with normal findings at nasopharyngoscopy. It suggests that nasopharyngeal swabs with LMP-1 detection could detect early recurrence, which, after salvage surgery, may actually improve local control and enhance survival. The detection of LMP-1 with subsequent verification of EBNA-1 from nasopharyngeal swabs in NPC patients treated with radiotherapy predicted local recurrence with a sensitivity of 91.7% and a specificity of 98.6%.
Nasopharyngeal swabs coupled with LMP-1 and EBNA-1 detection is simple and convenient, and it has proved to be a reliable method in detecting local recurrence in NPC patients after RT. The detection and removal of local recurrence in the early phases may improve local control as well as enhance patient survival.