Optimal Management of Limited-Stage SCLC

Transcript: Stephen Liu, MD: Surgery has a very small role in the treatment of small-cell lung cancer. For patients with a true stage I small-cell lung cancer, surgery can be considered and is incorporated in our current guidelines. This is based primarily on retrospective data in which patients with stage I small-cell lung cancer who underwent surgical resection had a very good prognosis. It’s important to remember stage I small-cell lung cancer is exceedingly rare, and most patients who are thought to have stage I small-cell lung cancer end up being upstaged at the time of surgery with occult lymph node involvement or metastases detected shortly after surgery.

It’s important that when stage I small-cell lung cancer is considered, that staging really is exhaustive, including biopsies of mediastinal lymph nodes, a PET [positron emission tomography] scan, and MRI [magnetic resonance imaging] with and without contrast. If there are certain cytopenias, even a bone marrow biopsy is recommended. Really, an exhaustive staging work-up is necessary because stage I small-cell lung cancer is truly quite rare. And if nodal involvement is identified, those patients aren’t really going to benefit from surgery, and all we’re doing is really delaying the therapy that they need.

If a stage I small-cell lung cancer truly is identified—where lymph nodes are biopsied and benign and no distant metastases are identified—surgery can be considered, in part because at times those will not be small-cell lung cancers. They will be other neuroendocrine tumors or atypical carcinoids, which on a fine-needle aspirate may resemble a small-cell lung cancer. If it is a different type of neuroendocrine tumor, then surgery is quite appropriate. So it can be considered but is very unlikely, and primarily, small-cell lung cancer is not a surgical disease.

Benjamin P. Levy, MD: What we need to remember about small-cell lung cancer is that roughly 30% of patients have limited-stage disease, where the goal is really cure. This is a very different approach from extensive-stage small-cell lung cancer, where we’re just giving chemotherapy. For limited-stage disease, we’re really looking at concurrent chemoradiation, or chemotherapy with radiation, most commonly platinum-etoposide with radiation. There have been some data in the past 5 years to look at optimal dosing of radiation with chemotherapy.

The CONVERT trial was a trial looking at single-dose radiation, or radiation dosed daily versus bid [twice-a-day] radiation concurrently with chemotherapy. This was a superiority trial trying to prove that daily radiation was superior to twice-a-day radiation. That trial failed to meet its end point, and because of that, I think we still consider bid radiation dosing to be the standard of care concurrently with chemotherapy. That’s what we try to do at our own institution: concurrent chemoradiation with platinum-etoposide with bid dosing of radiation for limited-stage small-cell lung cancer.

Stephen Liu, MD: Prophylactic cranial irradiation [PCI] does seem to have a role in the treatment of small-cell lung cancer, but its role is currently evolving. For limited-stage small-cell lung cancer, we know through our collective experience that the brain is a reservoir site. Patients unfortunately often relapse in the brain. Based on that natural history and the tropism for CNS [central nervous system] spread, low-dose radiation to the brain or prophylactic cranial irradiation, PCI, was explored in patients with small-cell lung cancer: initially in limited-stage disease with a complete response, later in limited-stage disease with any response and extensive-stage small-cell lung cancer. Both groups seem to derive benefit from prophylactic cranial irradiation. These studies are quite old, but in those studies patients who received PCI versus those just observed did seem to derive a benefit in the form of a decreased risk in the development of brain metastases and an improvement in overall survival.

The flaws with many of those early trials is that MRI [magnetic resonance imaging] screening for the presence of occult brain metastases was typically not performed. This really called into question the value of PCI in the extensive-stage setting. The phase III trial of PCI versus observation was replicated in a Japanese population but with the use of MRI, both at screening and during the period of surveillance. This eliminates occult brain metastases from being included in the population.

And with the use of MRI in the current era, PCI was still associated with a decrease in the incidence of brain metastases but did not confer that survival benefit. So a decrease in brain metastases without an improvement in survival, but at a cost—not simply a financial cost of radiation, but really a cost in neurocognitive capabilities—really called into question the value of PCI. It is no longer necessarily incorporated in all patients with extensive-stage small-cell lung cancer. Does that extend to limited-stage small-cell lung cancer? We simply don’t know. However, it certainly has called into question the role for every patient. It is worth a lengthy discussion with patients. Really, a shared-decision model is necessary until we have data in the limited-stage setting.

Benjamin P. Levy, MD: I think we need to remember that while we’re trying to cure patients with limited-stage small-cell lung cancer with concurrent chemoradiation, unfortunately the median survival for these patients is still only 18 to 22 months in some series. The 5-year survival rate for treated limited-stage small-cell lung cancer is only 10% to 12% or 10% to 15%. Unfortunately, the majority of patients do relapse, and this is an unmet need on how best to treat them. Yes, we’re going for cure, but most patients unfortunately—75% to 80% of patients—will relapse at some point, which really makes it challenging to treat these patients. And we’re coming up, of course, with new therapies in this setting to improve outcomes for these patients.

Transcript Edited for Clarity