A tale of two nodules
I was at the Royal society of Medicine in London a few weeks ago where a classic paradigm of lung cancer was discussed: when a patient with lung cancer presents with 2 nodules, how do you determine if they are synchronous or metastatic?
The premise for this question rests on the implications for further management. If the two nodules are synchronous, say 2 lesions that are T1 N0 M0 and T1 N0 M0 then it is assumed that complete resection of both will lead to a survival of a T1 N0 M0 tumour. On the other hand, if one is metastatic, then surgical resection would achieve survival of a T1 N0 M1 lesion.
Martini considered a second nodule to be synchronous if it was in situ, a different cell type and did not share the same lymph supply of the (presumably) distal nodule.(1) If these criteria were fufilled, the tumours could be considered as synchronous. There was a comment during the discussions that Martini made up these criteria, but if you think about it, they do make some sense.
The 6th revision of the UICC classification for lung cancer does not differentiate between synchronous and metastatic but considers a seperate nodule in the same lobe as T4 and in a different lobe as M1.(2) On conventional selection criteria patients with stage IIIB and IV are not considered for surgery.
I think all these arguments are flawed...
It’s cute to think that we can achieve the survival of the worst tumour with synchronous tumours, in Martini’s series the overall 5 year survival around 16%(1) clearly does not support the notion that synchronous tumours behave as separate lesions. More recent data have confirmed that patients with resectable lesions (especially in the same lobe) have excellent survival and certainly not reflective of a IIIB designation with a 3 year survival of 66% in patients with T4 and 63% in patients with M1 designations due to multiple nodules.(3 )The results are variable with French surgeons reporting 5 year survival of 34% in patients with an M1 designation (4), however all are favourable compared to 5 year survival of 5% and 1% with clinical IIIB and IV disease respectively.(2)
So where does that leave us?
I think we have no means to realiably distingush between metastatic and synchronous lesions, these patients do not have a post operative prognosis comparable to clinical stage IIIB / IV, but neither do they have a prognosis of two separate lesions - the post operative prognosis lies somewhere in between. The decision to proceed to surgery is ambigious and revolves around a concept that I love to survey: what is a 5 year survival that you and the patient would consider worthwhile to undertake the risks of a surgical operation (or two)?
The question itself is loaded, because it centres either around a relative benefit compared to untreated disease, or an absolute percentage survival. The former cannot be quantified, because we have no information on the outcome of comprative patients treated only by medical therapy, and therefore decisions are usually made on absolute survival. The conventional cut off is 40% or more (IIB), but the patient and surgeon may consider 30 or even 20% or more as worthwile, sadly many decisions are dichotomised into synchronuous - operate, metastatic - don’t operate without taking into account the ambiguity of classification, staging, post surgical outcome and most importantly - patient choice.
References
1. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. Oct 1975;70(4):606-612.
2. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest. Jun 1997;111(6):1710-1717.
3. Battafarano RJ, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA. Surgical resection of multifocal non-Small cell lung cancer is associated with prolonged survival. Ann Thorac Surg. October 1, 2002 2002;74(4):988-994.
4. Trousse D, Barlesi F, Loundou A, Tasei AM, Doddoli C, Giudicelli R, Astoul P, Fuentes P, Thomas P. Synchronous multiple primary lung cancer: an increasing clinical occurrence requiring multidisciplinary management. J Thorac Cardiovasc Surg. May 2007;133(5):1193-1200.