Chemoradiotherapy Before Surgery Improves Outcomes in Patients With Rectal Cancer

March 1, 2004

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

SALT LAKE CITY-Comparedwith patients with locally advancedrectal cancer who receivechemoradiotherapy postoperatively,those who receive chemoradiotherapypreoperatively have a downstagingof their cancer at surgery, a lower rateof local recurrence, a higher rate ofsphincter preservation when tumorsare low-lying, and a lower rate of adverseeffects, according to early resultsof the German Rectal Cancer Study(CAO/ARO/AIO-94). Lead authorRolf Sauer, MD, director of the Strahlenklinik,Erlangen, Germany, presentedthe results at the 45th Annual Meetingof the American Society forTherapeutic Radiology and Oncology(ASTRO plenary session, abstract 2)."Because of the radiobiological advantagesthat preoperative radiotherapyor chemoradiotherapy provides,the German Rectal Cancer StudyGroup in the mid-90s started this protocol,which compared neoadjuvantvs adjuvant chemoradiotherapy," Dr.Sauer said.Patients were enrolled in the phaseIII randomized trial from 26 institutions;they had stage II or III rectalcancer (T3/T4 or N-positive disease),as diagnosed by endorectal ultrasoundor the Mason procedure, and wereyounger than 75 years, Dr. Sauer said.They were assigned to preoperativeor postoperative concurrent chemotherapyand radiation therapy,consisting of 50.4 Gy in 1.8-Gy frac-tions and a continuous fluorouracil(5-FU) infusion over 120 hours duringthe first and the fifth weeks ofradiation therapy, and then four coursesof adjuvant maintenance 5-FU. Patientsin the postoperative chemoradiotherapyarm also received a 5.4-Gyboost.All patients underwent total mesorectalexcision at an interval of 4 to6 weeks from chemoradiotherapy. "Toexclude the impact of the surgeon as awell-known prognostic factor in rectalcancer treatment, stratification wasdone on the individual surgeon. Thisis unique in all randomized trials sofar," Dr. Sauer said.Outcomes were assessed during amedian follow-up of 43 months (range,4 to 89 months) in 405 patients givenpreoperative chemoradiotherapy and394 patients given postoperativechemoradiotherapy, Dr. Sauer said.According to intention to treat,patients in the preoperative chemoradiotherapygroup had a 5-year rate oflocal recurrence that was half that ofpatients in the other group (6% vs12%, P = .006).The 5-year rates of distant recurrencewere similar (30% for preoperativetherapy vs 34% for postoperativetherapy), as were the rates of diseasefree(65% vs 61%) and overall survival(74%). "Until now, the incidence ofdistant metastases has been equal inboth groups, which is why we have notseen an improvement in disease-freeor overall survival," he noted.About one-third of patients in eachtreatment group experienced anygrade 3/4 acute toxicity from thechemoradiotherapy (28% vs 40%), butrates of severe diarrhea were markedlylower in the preoperative chemoradiotherapygroup. Patients in the preoperativechemoradiotherapy grouphad a significantly lower rate of chronictoxicity in terms of anastomotic sitestenosis (4% vs 12%)."There was no evidence of perioperativeand postoperative surgicalcomplications after preoperativechemoradiation. The complicationrates have been very low," Dr. Sauersaid.Preoperative chemoradiotherapyresulted in a highly significant downstagingof cancer at surgery, with about8% of patients in this group having apathologically confirmed completeremission and stabilization of lymphnode metastases, Dr. Sauer reported.The International Union AgainstCancer (UICC) stage distributions atsurgery for patients in the preoperativeand postoperative groups, respectively, were as follows: stage I (25% vs18%), stage II (29% vs 28%), stage III(26% vs 39%), and stage IV (6% vs7%), with stage unknown for somepatients (6%, P = .0001).Before randomization, surgeonspredicted that 188 patients with lowlyingtumors would need abdominoperinealresection, Dr. Sauer said. Inthis subgroup, rates of sphincter preservationat the time of surgery weretwice as high among patients who receivedpreoperative chemoradiotherapyas among those who received postoperativechemoradiotherapy (39% vs19%, P = .004)."The conclusion of these first resultsis that preoperative chemoradiotherapysignificantly improved localcontrol, improved sphincter preservationin low-lying tumors, and reducedacute and chronic toxicity. Andso we anticipate that preoperativechemoradiation should be the newstandard treatment for advanced rectalcancer, at least in Germany,"Dr. Sauer said.