PURPOSE:The purpose of this prospective study was to determine the ability of fluorine‐18 fluorodeoxyglucose positron emission tomography to assess extent of pathologically confirmed rectal cancer response to preoperative radiation and 5‐fluorouracil‐based chemotherapy.METHODS:Patients with primary rectal cancer deemed eligible for preoperative radiation and 5‐fluorouracil‐based chemotherapy because of a clinically bulky or tethered tumor or endorectal ultrasound evidence of T3 and/or N1 were prospectively enrolled. Positron emission tomography and CT scans were obtained before preoperative radiation and 5‐fluorouracil‐based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5‐fluorouracil with leucovorin) and repeated four to five weeks after completion of radiation and 5‐fluorouracil‐based chemotherapy. In addition to routine pathologic staging, detailed assessment of rectal cancer response to preoperative radiation and 5‐fluorouracil‐based chemotherapy was performed independently by two pathologists. Positron emission tomography parameters studied included conventional measures such as standardized uptake value (average and maximum), positron emission tomography‐derived tumor volume (size), and two novel parameters: visual response score and change in total lesion glycolysis.RESULTS:Of 21 patients enrolled, prospective data (pretreatment and posttreatment positron emission tomography, and complete pathologic assessment) were available on 15 patients. All 15 demonstrated pathologic response to preoperative radiation and 5‐fluorouracil‐based chemotherapy. This was confirmed in 100 percent of the cases by positron emission tomography compared with 78 percent (7/9) by CT. In addition, one positron emission tomography parameter (visual response score) accurately estimated the extent of pathologic response in 60 percent (9/15) of cases compared with 22 percent (2/9) of cases with CT.CONCLUSIONS:This pilot study demonstrates that fluorine‐18 fluorodeoxyglucose positron emission tomography imaging adds incremental information to the preoperative assessment of patients with rectal cancer. However, further studies in a larger series of patients are needed to verify these findings and to determine the value of fluorine‐18 fluorodeoxyglucose positron emission tomography in a preoperative strategy aimed at identifying patients suitable for sphincter‐preserving rectal cancer surgery.