41IN - Pursuing the NED condition in advanced colorectal cancer: Implcations for clinical practice and trial design

Date 30 September 2012
Event ESMO Congress 2012
Session Pursuing the NED condition in stage IV colorectal cancer
Topics Anticancer agents
Colon and Rectal Cancer
Biological therapy
Presenter Alberto Sobrero
Authors A. Sobrero1, A.A. Cogoni2
  • 1Oncologia Medica, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 2Medical Oncology, "SS. Annunziata" Hospital, 07100 - Sassari/IT


Cure is the most relevant endpoint in cancer treatment. Next comes OS followed by DFS. Cure actually transits through DFS of sufficiently long duration to assure no relapse. Hence the value of DFS and its link to cure. The appeal of getting a NED state is so strong just because of this link. However its clinical value is dependent upon two factors: the toxicity of the multimodal intervention and the duration of the NED state. If the absence of disease lasts 12 months, giving the patient the hope for cure during this period, anybody may consider this a meaningful result; but if RFS lasts only 4 months and the “toll” paid by the patient has been substantial, this is clearly an irrelevant benefit. The heart of the issue is that whenever a treatment has the potential of rendering the patient NED, we should consider it, but at the same time we should not be deceived by this perspective if the chances of benefit are too remote, as it is in the great majority of cases. Therefore our strategic choice towards aggressive programs should not be guided by eradicating all visible tumor deposits (technical feasibility), but by how high the chances are of obtaining a DFS of at least 6-12 months. There are a series of concepts and data guiding us between what is technically feasible and what is oncologically sound. First, curability of stage IV may be as high as 50% in very selected case series, but in unselected cases curability is extremely low, 1 to 4% in non-dedicated randomized trials. Second, whenever we “push” for very extensive surgery, the median RFS is < 12 and sometimes < 6 months. Third the disease might accelerate its course under the “shower” of wounds–related growth factors. Fourth, toxicity and costs of these approaches are very high. The contrast between the appeal (and sometimes strong benefit) of the NED state and the questionable clinical value of this condition, when short lived, has implications on both clinical practice and the design of clinical trials. Wrong deviations from the classical palliative systemic treatment, pursuing miraculous results, but actually promoting clinical deterioration, are the most common consequences of these approaches in practice. Very high originality and relevance, but low intrinsic and external validity of the results are the classical features and limits of the trials designed and conducted in this field.


All authors have declared no conflicts of interest.