Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks?

PURPOSE: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-d-glucose-labeled positron emission tomography/computed tomography ([(18)FDG]PET/CT) imaging and correlate with response to CRT. METHODS AND MATERIALS: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials.org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study after 1 h (early) and 3 h (late) from (18)FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered "bad" responders and the others as "good" responders. RESULTS: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were "good" responders. "Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of "good" response (accuracy of 67%). CONCLUSIONS: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.

Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean?

PURPOSE: The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. METHODS: Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. RESULTS: Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P<0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P=0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P=0.2), and both were significantly better than patients with ypN+ disease (30 percent; P<0.001). CONCLUSIONS: Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.