A look at the disease's trends and treatments

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Lung cancer remains the leading cause of cancer death in the United States, even though the death rate decreased from 2015 to 2019. For help understanding what's happening with lung cancer, I'm talking with Dr. Stephen Graziano. He's professor of medicine and chief of hematology and oncology at the Upstate Cancer Center, and many of his patients have lung cancer. Welcome back to "The Informed Patient," Dr. Graziano.

[00:00:39] Stephen Graziano, MD: Thank you, Amber.

[00:00:41] Host Amber Smith: What can you tell us about the latest statistics for lung cancer in terms of survival?

[00:00:47] Stephen Graziano, MD: Well, it's a long trajectory of statistics for lung cancer. When I started as a fellow back in 1982, the long-term survival for lung cancer, and by that we mean five-year survival, was probably in the eight to 10% range. With 40 years of research and improvements in treatments we're probably up to 25 to 30% five-year survival for lung cancer.

[00:01:16] Host Amber Smith: So it's improving?

[00:01:19] Stephen Graziano, MD: It is improving. And, not captured in those statistics are the average patient is living longer. But reflected in the five-year survival, we're still in that range of 25 to 30%.

[00:01:33] Host Amber Smith: Are there differences between women and men?

[00:01:37] Stephen Graziano, MD: So the difference between women and men mostly has to do with the incidence of smoking. You know, men probably had double the rates of smoking going back to the '60s when the Surgeon General's first report came out. I would estimate that probably about 40, 45% of men smoked and maybe about half the rate for women. So those rates have come down markedly, and I think that's probably driving most of the decrease in mortality for lung cancer.

I checked this in anticipation of your question. Currently about 13% of men smoke. And about 10% of women smoke. So that's just a huge epidemiologic difference in what we're seeing. And that, of course, is reflected in the mortality from lung cancer.

The mortality for men probably peaked around 1990 and has been coming down several percent per year since 1990, 2 to 4% per year, which is a huge difference. For women, they started smoking a little later than men, and they probably peaked out around 2000, and then their rates are coming down as well. But I think what's different now is we're also seeing some of the newer therapies also making an impact. So the reduction in mortality is not just decrease in incidence, but I believe treatments are also influencing the reduction of mortality as well. That's a first.

[00:03:07] Host Amber Smith: The American Cancer Society says 10 to 15% of lung cancers are small cell lung cancer, and the rest, 80 to 85%, are non-small cell lung cancer. Which is the one that's more common in smokers?

[00:03:22] Stephen Graziano, MD: So all are increased in smokers, compared to non-smokers. Small cell is most strongly associated with heavy smoking. Next would be squamous cell cancer, and then next would be adenocarcinoma. So adenocarcinoma is the subtype which makes up, now, about 60% of newly diagnosed cases, but that is the one associated with non-smoking most commonly and, also, with a lot of the cancer mutations that you see in the news where there are targetable mutations and agents that will attack those targets.

[00:03:58] Host Amber Smith: So there's an increase in lung cancers in people who never smoked?

[00:04:03] Stephen Graziano, MD: I wouldn't say that. We've always seen some lung cancer in non-smokers. It's probably in the 10 to 15% range.

[00:04:11] Host Amber Smith: Well, let me ask you this: Is vaping as dangerous as cigarette smoking in terms of the lung cancer risk?

[00:04:20] Stephen Graziano, MD: I think it's too early. I think there's a growing concern about vaping as exposing the lungs to carcinogens, but I think it just hasn't been around long enough to see increases in lung cancer in that group.

[00:04:36] Host Amber Smith: Regarding lung cancer screening that's been available in recent years, have enough people done this so that it's helping to reduce mortality?

[00:04:47] Stephen Graziano, MD: I am glad you raised that point. I think this is an area where we're falling short. The U.S. did a large study looking at screening CT scans. And then the Europeans did a trial called the NELSON trial that was reported about four years ago. And both showed marked reductions in mortality with the uptake of screening CT scans.

So probably only about 20% of people are getting low dose screening CT scans, that are eligible. So I think we need to do a lot better in this area. We do Pap smears for cervical cancer, PSAs for prostate cancer, colonoscopy for colon cancer, which have all made impacts in those diseases. I think we have a great opportunity to decrease mortality further by doing low dose screening CT scans.

Now, the criteria for this is, if you've smoked one pack a day for 20 years, that's called 20 pack years, and you're between the ages of 50 and 80, and you quit smoking less than 15 years ago. That's the criteria now for someone to be eligible for a low dose screening CT scan. And the nice thing about the low dose screening CT scan is, it exposes patients to minimal radiation, but it's quite accurate. We have algorithms for what do you do if there's a nodule that's picked up on that CT scan. So, we're pretty sophisticated in terms of how to manage the small pulmonary nodules that might be picked up on a CT scan.

[00:06:27] Host Amber Smith: Is it Medicare that pays for those screenings, or are private insurers? Because you said someone age 50 and up could qualify for this, but if you're 50, you're probably not on Medicare.

[00:06:39] Stephen Graziano, MD: Insurance should be covering it. It is approved by the FDA, (Food and Drug Administration.) And all the large organizations, preventative organizations, the National Comprehensive Cancer Center Network guidelines. So yes, it should be covered.

[00:06:55] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Stephen Graziano. He's a medical oncologist at the Upstate Cancer Center, and we're talking about lung cancer.

You mentioned that some of the improvement in survival has to do with treatment, so I wanted to ask you about some of the treatment advances that have helped with that. What does treatment usually consist of these days for early stage cancers?

[00:07:23] Stephen Graziano, MD: So we can divide lung cancer into basically one-third, one-third, one-third.

So one-third present with early stage disease where surgery is the main treatment for those patients. One-third present with disease that has spread to the lymph nodes in the middle of the chest. That's stage 3 disease, and that's approached in a different manner. And then stage four is when it has spread to distant sites. So about one third of patients present in that way.

So for the first group, the early stage patients, they generally undergo surgery, and if they have certain characteristics, they would be eligible for what we call adjuvant chemotherapy. So if they have lymph nodes involved and their risk is over 50% of for recurrence, we generally will treat them with about three months of chemotherapy. And then immunotherapy has just come online the last two years, which was also making a big impact in preventing recurrences. So, for early stage disease, it's surgery. And then for certain patients at higher risk, they'll get chemotherapy and immunotherapy.

For the middle group, for the stage three patients with lymph nodes involved, generally we will treat with a combination of radiation and chemotherapy, followed by one year of immunotherapy. This was also a huge step forward for patients. Cure rates went from 20% up to nearly 50% with that approach. So research is building on that, adding to that backbone of treatment.

And then for advanced stage disease, the biggest difference is we are identifying patients that have genetic mutations where we might have oral agents that will treat these targets. Probably around 40% of advanced lung cancer now will have a target of some sort where we have not just chemotherapy and an immunotherapy, but we also have oral agents that can be effective. So that adds to our armamentarium of chemotherapy and immunotherapy for patients with advanced disease.

[00:09:36] Host Amber Smith: So it sounds like a lot more options. A as soon as someone gets diagnosed, is this a cancer that needs to be dealt with pretty immediately?

[00:09:46] Stephen Graziano, MD: I would say in general, yes. Small cell is particularly an aggressive disease, so once you make a diagnosis of small cell, you really want to get patients treated within a week or two.

For non-small cell lung cancer, they're a little less aggressive, and usually you can take your time. That's a situation where you want to send their tumor for a genetic testing and testing for PD-L1, which will predict which patients benefit from immune therapy. So usually not as have as much of a rush for non-small cell, but you want to get in on treatment within probably two or three weeks after diagnosis.

[00:10:24] Host Amber Smith: What are the survival rates for each of these thirds? The early, the middle and the later stage?

[00:10:30] Stephen Graziano, MD: So for early stage patients, we're probably looking at, oh, 70 to 80% long-term survival. For the middle group, we're probably looking at three to four year average survival, but cure rates in the 50% range. And for advanced stage disease, this is actually where the biggest changes have been seen. We used to not see much, a high percentage of long-term survival, so maybe five-year survival in the single digits, you know, 3%, 4%.

Now, remarkably with the advent of immune therapy, we're seeing close to 20% five-year survival for patients with stage four disease. That is truly a remarkable achievement and obviously a long way to go. But, there are patients that have been treated with chemotherapy and immunotherapy, and the current standard of practice is to treat patients for two years. If they're in remission after two years, you discontinue therapy and put them on surveillance. And patients remain in remission for months and years off therapy.

My earliest patient where I discontinued therapy was February of 2018, and she had stage four disease. She remains in remission. And I just see her periodically in clinic. It's quite remarkable.

[00:11:53] Host Amber Smith: That is encouraging. Do you anticipate that lung cancer survival rates are going to continue to improve?

[00:12:00] Stephen Graziano, MD: I do. There are some roadblocks. For patients who become resistant to immune therapy, we're looking at ways to reestablish sensitivity to immune therapy. So there's a lot of strategies that are being looked at in research and clinical trials to try to reestablish sensitivity to immune therapy.

[00:12:22] Host Amber Smith: Well, Dr. Graziano, thank you so much for taking your time for this interview.

[00:12:26] Stephen Graziano, MD: Thank you for asking.

[00:12:27] Host Amber Smith: My guest has been Dr. Stephen Graziano. He's professor of medicine and chief of hematology and oncology at the Upstate Cancer Center. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.