This transcript has been edited for clarity.
Hello. I’m Mark Lewis from Medscape. I will be coming to you in the summer of 2023 after the ASCO Annual Meeting. I went into this conference with high hopes that it would change my practice, and it did. But what I wanted to talk about today was some of the controversy surrounding one of the most prominent studies ever published.
This was the second year in a row that the conference received intense coverage in both the scientific press and mainstream media. in this case, new york times. Oddly enough, both cases concerned the management of rectal cancer.
In 2022, new york times I posted this headline. “Unexpected result of cancer clinical trial: all patients in remissionThis is a large, attention-grabbing headline about a small but important study conducted by colleagues at Memorial Sloan Kettering that investigated the role of dostarlimab in locally advanced, MSI-high rectal cancer. All patients in this study ended up in the low double digits, but they responded to the immunotherapy and did not require chemotherapy, radiation therapy, or surgery. As we know, this is traditionally a disease and probably the most prominent gastrointestinal malignancy that requires a trimodal approach.
The situation was not much different this year. Sunday, June 4th, new york times The heading is “Rectal cancer patients may be spared the brutal effects of radiationAfter considerable uproar, by the next day the word “brutal” was diplomatically removed from future editions, although the edit was already included in the original title.
Now, with all due respect to the archives, I think the appropriate word here is “détente,” but that unfortunate phrasing belies the fact that this is precisely the hard work we should rightly celebrate. There is a risk that it will be covered up. our biggest stage. Dr. Schrag beautifully explained the rationale in his plenary presentation. PROSPECT Trial. In fact, let me quote her here.
Preoperative chemoradiotherapy has been the standard of care for the past 20 years because of its lower toxicity and lower pelvic recurrence rates than postoperative therapy. When PROSPECT was launched in 2012, the common approach to curative intent treatment for locally advanced rectal cancer was 5.5 weeks of pelvic chemoradiotherapy, then surgery with total mesorectal resection, and finally, after recovery. Adjuvant chemotherapy (usually 8 cycles of FOLFOX or 6 cycles) was given. CAPOX’s.
Although this approach cures approximately three-quarters of patients and keeps local recurrence rates in the single digits, this treatment is expensive. Pelvic chemoradiotherapy has significant long-term toxicities, including impairment of bowel, bladder, and sexual function, and increased risk of pelvic fractures, second malignancies, impaired bone marrow reserve and fertility, and even premature menopause. To do. And because rectal cancer is increasingly being diagnosed in people under the age of 50, it’s a huge problem.
I think Dr. Schragg actually made a very fair and balanced judgment in how he presented our desire to make a trade-off between reducing toxicity and maintaining efficacy. As a medical oncologist, I always tell my patients that for treatment he needs two things. But in many cases, even before efficacy can be determined, a treatment must be safe and tolerable.
One of the biggest challenges to changing my practice in my entire career was IDEA researchThis paper, presented at the ASCO Annual Meeting more than five years ago, examined outcomes based on 3 months versus 6 months of adjuvant oxaliplatin-containing therapy (FOLFOX or CAPOX) for stage III colon cancer. This is what I did.
The discovery that a significant number of my patients could have their duration of adjuvant chemotherapy halved and the incidence of chemotherapy-induced neuropathy reduced by two-thirds was a great opportunity for me, and for the entire nation and… It was an immediate practice changer for thousands of oncologists around the world. world.
Nor should researchers be penalized if results from such trials take years to become available, knowing that standards of care will also change during enrollment and as data mature. Dr. Schrag also agrees:
Over the past 20 years, advances in chemotherapy, the development of FOLFOX, surgical techniques with total mesorectal resection, widespread screening leading to fewer T4 and large symptomatic tumors, and pelvic MRI have improved the accuracy of staging. Improved.
Taken together, these advances led researchers to hypothesize that they could de-escalate treatment and use chemoradiotherapy selectively without compromising outcome.
Again, a well-explained rationale. Dr. Schrag also said that even at his very same ASCO conference, Prodigy 23 The researchers presented data on FOLFIRINOX as part of an overall neoadjuvant therapy approach, also prior to total mesorectal resection in rectal cancer.
I think this de-escalation effort is critical because less can be more, or at least no less, in terms of cancer-related outcomes while improving patients’ quality of life. thinking about. That’s also important — new york times “Brutal” headlines aside, the reason we tout these findings is that we have no interest in doing more for the sake of more. This is because I believe that they are truly and authentically demonstrating this to the people. We are interested in doing less if it has less negative impact on the patient.I’ll go back again Primum non nocere As our important medical guideline.
Overall, I think PROSPECT is a practice-changing study. As Dr. Schrag said best during the plenary session, this does not eliminate the need for interdisciplinary discussion of rectal cancer cases. Again, I cannot manage locally advanced rectal cancer without discussing every case with a radiation oncologist and surgical oncologist.
We are aware of other articles that describe PROSPECT’s schema and generalizability from a patient perspective in more detail. I think the overarching message here is that détente is something to be celebrated, not criticized. Rather than explaining that brutal treatments have been omitted, we can provide similar benefits to patients when it comes to cancer, while reducing harm to patients regardless of treatment. That fact should be celebrated.
Signed by Mark Lewis of Medscape.
Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City, Utah. He is interested in neuroendocrine tumors, inherited cancer syndromes, and patient-physician communication.
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