WCLC 2025 | Recent developments in limited-stage small cell lung cancer

The basis of my talk was to really delineate what the current challenges and perspectives in small cell lung cancer are. So to give an overview, we have made significant progress in treating these patients. In limited-stage small cell lung cancer, even if the patients don’t get immunotherapy, just the standard previous treatment, giving radiotherapy concurrently with chemotherapy have probably improved median survival now, at about 30% five-year survival. And part of the reason for that was just stage shift. We stage the patients better now, so we detect metastases much more frequently in our patients. So that would shift, and it would make the current treatments work better because you’re treating the right people. The second reason is the techniques that we use for radiotherapy, where they’re much more conformal. They can actually treat the disease much better. And then we have this twice-daily versus once-daily treatment, which is, you know, the sense is that it may be a little bit better than the once-a-day treatment, and there are a number of other factors that I think are emerging as important for limited-stage small cell lung cancer. One is the whole area of should we give patients prophylactic cranial irradiation. This is a controversial area now because the patients, because we’re giving immunotherapy and their lives are getting lengthened, you know, out to four years, over four to five years median survival, and those patients are more likely to get cognitive impairment over time. So, should we give it, or can we just observe the patients more closely? So, there are trials that are going to compare prophylactic cranial radiation given upfront versus those patients who go along and have observation, and those observation, if when they relapse, they can then go have either prophylactic cranial radiation or a more targeted therapy for the lesions that come back. They’re going to be very important in the future, defining how we look after patients. And when we talk about patients in the clinic, um, you know, people are concerned about loss of cognition, like it is a big problem, you know, the brain fog, and, and, and, you know, people are concerned about this. So, a lot of people do have no issue with not having the PCI, they just have being in that observation arm, and so I think, I think that’s, these are going to be important trials. The other thing that’s emerging as well for small cell limited stage is the dose. It looks like a higher dose may actually work better than the standard doses now. There are two randomized control trials, one from China, one from Norway. There’s certainly a point in that direction, and when you do subset analyses of the other trials I’ve mentioned, again, there seems to be a benefit for that, for you know, the higher dose of treatment. So, yeah, it’s certainly an area of interest in improving things. So, our challenge is to do the right trials to make sure the best treatments are given to the patients, which is, you know, as I mentioned, chemoradiation followed by immunotherapy at the moment. Do we give PCI or not? Maybe. Do we give higher doses or not? Maybe. And how do we best incorporate radiation into the treatment with IO therapy at the same time? So, chemoradiation and IO at the moment, that’s a little concerning because the patients certainly don’t seem to be doing any better. So, we’ve got to look at other strategies.

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