723 Background: Isolated pelvic perfusion (IPP) may improve disease control and facilitate pelvic resection in selected high-risk patients with advanced recurrent rectal cancer by reducing painful tumor burden and lessening chances of recurrence. Methods: IPP was done in 42 patients with locally advanced previously irradiated rectal cancer, 26 as preoperative therapy and 16 for palliation. A comparative larger non-perfused group included 63 patients with pelvic resection only via abdominal sacral resection (ABSR) for recurrent rectal cancer. Isolated pelvic perfusion (IPP) with a pump oxygenator, (temp > 41ºc), delivered sequential (q 10 minutes) chemotherapy:– 5FU (5fluorouracil) 1,500 mg/m2, cisplatin/oxaliplatin 100/150 mg/m2, mitomycin 10mg/m2, for 60 minutes in 42 patients. Results: Palliative IPP in 16 advanced rectal cancer patients resulted in significant relief (1–4 months) of narcotic resistant pain (in 70%). Pre-operative IPP in 26 locally advanced rectal cancer patients achieved a clinical path (CR) in 2 patients, and significant regression in 11 patients rendering them resectable. Seven had RO pelvic resections. Of 6 other patients, 4 refused surgery, 2 were medically excluded. Median survival was 30 months in 7 resected patients (all had RO resections) and 2 were 5-year survivors. This is compared to outcome in 63 patients having pelvic resection alone for recurrence: 57 % had RO resection (median OS = 36 months), 28% had R1 resection (median OS = 15 months) and 15% had R2 resection (marrow invasion) (median OS = 21 months). Conclusions: Neoadjuvant IPP may facilitate resection of advanced or (borderline resectable) recurrent rectal cancer by reducing tumor bulk and identifying therapeutic responders likely to benefit from major pelvic resection while excluding non-responders mostly likely to benefit from non-surgical therapy. The potential to induce regression and facilitate RO resection merits further exploration