Capecitabine and Oxaliplatin Prior and Concurrent to Preoperative Pelvic Radiotherapy in Patients With Locally Advanced Rectal Cancer: Long-Term Outcome.
The risk/benefit ratio of any treatment can only be fully assessed if long-term results of both efficacy and toxicity are taken into account. Whereas the combined modality treatment of locally advanced rectal cancer (LARC) has considerably improved prognosis, particularly with regard to local control, long-term results-including patient-reported outcomes-are underreported.



Patients with LARC treated within a multicenter single-arm phase II study were prospectively assessed for at least 5 years after surgery. Study treatment consisted of capecitabine and oxaliplatin prior and concurrent to preoperative pelvic radiotherapy followed by total mesorectal excision. Progression-free survival time (first endpoint), overall survival time, and pattern of relapse were analyzed in the whole study population and in pre-planned exploratory subgroups. Patient-reported outcomes, including overall satisfaction with bowel, stoma, and urinary function, were assessed in 6-month intervals.



Five-year progression-free and overall survival rate was 61% (95% confidence interval [CI], 46%-73%) and 78% (95% CI, 63%-87%), respectively. Distant to local recurrence rate was 3:1, with only 8% of patients relapsing locally. Main predictors for recurrence in univariate analyses were tumor downstaging (hazard ratio, 0.16; 95% CI, 0.05-0.56; P = .0011) and nodal downstaging (hazard ratio, 0.17; 95% CI, 0.06-0.52; P = .0005). The self-reported burden of symptoms related to bowel function was high in up to one-third of patients. A total of 28% of patients were dissatisfied with their urinary, bowel, or stoma function for at least 1 observation period.



Combined-modality treatment of LARC results in a high and durable local disease control rate, especially in patients with tumor and/or nodal downstaging, at the cost of relevant long-term toxicity. Long-term care is required for a proportion of patients with poor gastrointestinal and/or urinary function after multimodality therapy. Reporting of long-term follow-up, including patient-recorded outcomes should be mandatory for future trials in LARC.
Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. Electronic address: viviane.hess.@usb.ch.
Viviane
V
Hess
Department of Medical Oncology, Cantonal Hospital, Lucerne, Switzerland.
Ralph
R
Winterhalder
Department of Medical Oncology, Cantonal Hospital Graubunden, Chur, Switzerland.
Roger
R
von Moos
Department of Medical Oncology, Hospital Triemli, Zurich, Switzerland.
Lucas
L
Widmer
Roche Pharma Schweiz AG, Medical Affairs, Reinach, Switzerland.
Priska
P
Stocker
Department of Medical Oncology, Hospital Triemli, Zurich, Switzerland.
Monika
M
Jermann
Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Richard
R
Herrmann
Department of Medical Oncology, Cantonal Hospital, St. Gallen, Switzerland.
Dieter
D
Koeberle
D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine / Q000008:administration & dosage; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine
Adenocarcinoma of the rectum; Combined-modality treatment; Long-term follow-up; Neoadjuvant downstaging; Patient-reported outcomes