This is the first part of a case presentation I did with two great colleagues: Dr. Anne Tsao, who is a medical oncologist and lung cancer expert at MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, who is a terrific thoracic surgeon at my own institution, Swedish Cancer Institute in Seattle.
In my last post I wrote about the prognostic value of molecular markers like EGFR and K-Ras that have generally been studied in patients with advanced NSCLC and treated with EGFR inhibitors, but these studies looked at prognosis in patients with early stage NSCLC who underwent surgery. These studies also provided some interesting results on the prognostic value of some clinical variables as well.
One of the issues that we've commonly discussed and debated here is the question of when a local approach like surgery and/or radaition may be appropriate for I recently saw a patient of mine who I first met more than four years ago. At that time, he was only 37 years old and had just been diagnosed with stage IIIA NSCLC with several N2 nodes involved, after having quit smoking a couple of years earlier. He had actually initiated treatment with another local oncologist, a plan of chest radiation along with concurrent weekly carbo and taxol.
In prior posts I've described the special circumstance of a Pancoast tumor, which is a tumor at the top of the lung that tends to grow into the spine, ribs, and sometimes the nerves going to the arm. These cases are a major challenge because surgery is often something to consider, because they often grow locally more than speading to the rest of the body, but surgery can be a special challenge because the vertebrae are generally not considered to be resectable.
Probably the most contentious areas of lung cancer management is stage IIIA NSCLC, with N2 nodal involvement, the nodes outside of the lungs, toward the middle of the chest but on the same side as the main tumor. One of the key issues is that the staging is the same whether there's a single microscopically involved lymph node or multiple enlarged lymph nodes in a few areas of the mediastinum (mid-chest, between the lungs). But the outcomes of these groups of patients is very different, so it may be worth thinking about them a little differently.
To begin with, my overall impression is that the preponderance of evidence on adjuvant (post-operative) chemotherapy supports that it can reduce the recurrence risk and improve the survival at five years, which I'd presume to be pretty close to the "cure rate". The benefit isn't uniformly distributed for all patients: higher risk patients, as defined by stage and other additional factors like number of lymph nodes involved and the grade of the cancer, also matter.
I had described earlier this week (prior post here) how the long-term follow up of one of the more important adjuvant chemotherapy trials for early stage resected NSCLC patients showed that there may be long-term adverse effects of chemotherapy. My last post also suggested that the benefit of pre-operative chemotherapy in another trial appeared to be limited to the patients with stage IIB and IIIA disease and wasn’t present for stage IB and IIA patients.
In my last post I described the results of the ChEST trial that showed a borderline statistically significant improvement in survival of patients who received cisplatin/gemcitabine chemotherapy for stage IB to IIIA NSCLC prior to surgery. This study was very similar to another neoadjuvant chemotherapy trial, known as SWOG 9900, which also randomized patients to upfront surgery or 3 cycles of pre-operative chemotherapy followed by surgery.
Pre-Operative Chemotherapy as an Alternative to Post-Operative Chemo: Evidence of Stage-Dependent Survival Benefit
In contrast with post-operative chemotherapy, which has become a standard treatment approach to reduce the probability of recurrence of resected stage II and IIIA NSCLC (still pretty controversial for stage IB), pre-operative chemotherapy (also known as neoadjuvant, or induction chemotherapy) is less well studied and isn’t a typical approach.
Over the past few years, the role of post-operative, also known as adjuvant, chemo has become increasingly accepted as a standard of care. Several trials have shown an improvement in survival at about 5 years that is in the 5-15% range for recipients of chemo.