Resectability is currently being discussed in the context of randomized controlled trials of neoadjuvant immunochemotherapy, which has been further fueled by the results of multiple papers recently presented at the American Society of Clinical Oncology’s 2023 Annual Meeting.
As part of these discussions, it is essential to sort out terminology, namely, to distinguish between “operability” and “resectability.” Operability refers to the patient’s status; resectability to the tumor itself. A tumor may be considered technically resectable yet deemed medically inoperable because of other criteria such as general health status, comorbidities, or high operative risk.
When defining resectability, IASLC President-elect Paul Van Schil, MD, PhD, once said “resectability is in the surgeon’s state of mind.”
Is it really?
In the real world it is. However, the definition of resectability in cancer patients ideally should be based on the assessment of whether R0 resection is possible. Ideally, that should be determined by a multidisciplinary tumor board.
In 2005, Ramón Rami-Porta, MD, PhD, on behalf of IASLC Staging and Prognostic Factors Committee, presented a definition of complete, incomplete, and uncertain resection. Complete resection (R0) is achieved when resection margins are free, systematic or lobe-specific nodal dissection has been performed, the highest lymph node station harvested is negative, and there is no extracapsular nodal involvement.
In our opinion, uncertain resection is tantamount to incomplete resection, for instance when carcinoma in situ is present in the bronchial margin or lymph node dissection has not been performed according to standard criteria.
Stage I and II non-small cell lung cancer (NSCLC) constitute a category of resectable tumors in almost 100% of cases. The feasibility of resection enters the discussion when we start to deal with stage IIIA NSCLC, and this requires specific assessment of T4 tumors and N2 status.
Several questions come to mind during these discussions.
Is “resectability” based on the criteria of radical resection presented above still valid in the era of neoadjuvant immunochemotherapy, when 30-68% of patients undergoing such treatment have major pathological response (mPR) with less than 10% residual viable tumor at the time of surgical resection? To what extent do mPR rates correspond to radiographic response by RECIST criteria? And how does evaluation of ctDNA serum levels inform assessment before surgery in gauging resectability?
With pathologic complete response (pCR) rates occurring in 15-40% of patients treated preoperatively, the term “resectability” needs to be revisited and probably redefined based on the tumor’s status pre-treatment and post-neoadjuvant treatment.
There is a surgical dogma regarding the extent of resection after neoadjuvant treatment—that it should closely match that before treatment. This notion also needs to be reconsidered in the light of perioperative adjuvant studies showing a high rate of both mPR and pCR.
In the future, pCR status will likely include assessment of biomarker levels; and given the profound benefits observed with immunotherapy in some individuals, one wonders if we shouldn’t reconsider re-evaluation of whether IIIB, IIIC, and IVA stages as potentially resectable? This question warrants further studies.
The groundbreaking results of recent neoadjuvant and perioperative trials combining chemo-immunotherapy and surgery require confirmation in the long term, but they provoke multiple considerations and discussions in the here and now.