Immune-based treatments for cancer have become the biggest new advance in tackling tumors, and the latest approval could make a big difference for some people with rectal cancer.

On Oct. 19, the U.S. Food and Drug Administration (FDA) approved dostarlimab (brand name: Jemperli) to treat a specific type of rectal cancer called microsatellite instability-high (MSI-H)/mismatch repair deficient cancer. This cancer is caused by the accumulation of certain genetic mutations that prevent rectal cells from repairing DNA damage and accounts for 5-10% of rectal cancers. In a study of 154 people with this type of rectal cancer who were treated with dostarlimab, 68% had a complete clinical response at one year, which meant doctors could not see evidence of tumors on imaging or other methods for tracking the tumors. In the study, which the drug's manufacturer, GSK, submitted to the FDA, people received nine infusions of the drug: once every three weeks for six months.

“Not only did they reach clinical complete response, but they maintained that for a year,” says Dr. Andrea Cercek, section head of colorectal cancer at Memorial Sloan Kettering Cancer Center and principal investigator of the study. (Some of the earliest patients have continued to remain tumor-free for even longer. ) “That really suggests that the response is durable and real.”

Dostarlimab is a checkpoint inhibitor, which means it releases the brakes that hold back the immune system from recognizing and attacking tumors. The drug allows immune cells to destroy cancer, making it a powerful weapon for seeking out cancer cells no matter where they spread or hide.

“We have completely leapfrogged over standard of care with a simple immunotherapy that melts the tumor away,” says Dr. Luis Diaz, head of solid tumor oncology at Memorial Sloan Kettering and one of the trial investigators.

The benefits of avoiding standard rectal-cancer treatment

Standard treatment for rectal cancer involves chemotherapy, radiation, and surgery to remove the rectum that requires patients to wear colostomy bags for the rest of their lives. The dostarlimab approval means more patients whose tumors have specific mutations could avoid those aggressive therapies altogether. “We have patients who would have lost the ability to bear children who have had children because this therapy replaced chemotherapy, radiation, and life-altering surgery in one swoop," Diaz says. "That’s a big deal.”

Kelly Spill is one of them. Diagnosed in 2020 when she was 29, shortly after having her first baby, Spill spent nearly nine months trying to figure out why she continued to have constipation and see bloody discharge in the toilet. Because she had recently given birth, doctors first attributed the symptoms to her pregnancy, and when they persisted after delivery, to internal hemorrhoids. It wasn’t until a doctor ordered a colonoscopy that they found a tumor.

“The doctor told me it was Stage III colorectal cancer, and that the treatment plan would include chemo, radiation, and surgery. And that I would never carry another baby again, and would most likely have a colostomy bag for the rest of my life,” says Spill. “It didn’t seem real until I heard the words that I was not going to carry another baby. I immediately stopped thinking about me, and started thinking about my husband and what it meant for my son. We had just started our lives together; we were supposed to have all these kids.”

Sascha Roth also faced devastating news when she was diagnosed with rectal cancer in 2019 after seeing blood in her stool. A resident of Washington, D.C., she had a friend with a similar diagnosis who had received chemotherapy, radiation, and surgery and recommended his surgeon at Memorial Sloan Kettering. Roth assumed she would follow the same strategy, but she learned that she had Stage III cancer and that she wasn’t a good candidate for surgery because the tumor was located so low in the rectum. Her tumor also had mutations that suggested it wouldn’t respond well to chemotherapy.

“It was a double whammy that threw me down,” she says. But the surgeon introduced her to Cercek, who was waiting to hear from the FDA about starting an immunotherapy trial for patients like Roth. “They told me I would be the first patient in the study, and there wasn’t scientific evidence that it would work.” Still, Roth wanted to try. She agreed to become Memorial Sloan Kettering’s first patient on the study, and then spent two months waiting for the FDA to greenlight the trial so she could begin receiving the drug. “I was calling Sloan Kettering incessantly to see if the FDA approved [the study],” she says. “The second the FDA gave its stamp of approval, Dr. Cercek’s team called me to New York to start the first round of treatment less than a week later.”

Not long after that, at Spill's first appointment at Memorial Sloan Kettering to discuss chemotherapy, she learned that the mutations on her tumor made her a good candidate for a study they had just begun. Only three patients had enrolled ahead of her (including Roth), so there was no data on whether it would actually treat her cancer. Spill, who was at the appointment with her mother, decided she had nothing to lose by joining the trial. “If it doesn’t go well, we could go back to option A,” Spill remembers her mother saying.

By her second infusion, Spill felt the tumor was shrinking because she no longer had major constipation. By the fourth infusion, scans showed the tumor had shrunk by 50%. The study originally called for patients to get chemotherapy, radiation, and surgery if needed after six months on dostarlimab. But a nurse pulled Spill’s mother aside after that appointment to tell her that the first three patients in the study did not need any additional treatments because their tumors had disappeared. Following Roth’s results, the study was revised to make chemotherapy, radiation, and surgery an option only if needed: if the tumors hadn’t gone away. It wasn’t a guarantee that Spill would have the same results as those first patients, but “it gave me hope, and all I could think about was maybe I could have another baby,” she says.

After all of her dostarlimab infusions, Spill, too, no longer had any tumor left and was declared cancer-free. Her doctors advised her to wait two years before trying to get pregnant again to ensure the cancer wouldn’t return. Once she was cleared, she got pregnant and gave birth to a girl in 2023, and later a boy in 2025. “I am now five years cancer-free, and last September got the boot from Memorial Sloan Kettering,” she says, meaning she no longer needs to follow up with her oncologists there. She now sees her primary care doctor for colonoscopies every two years.

“I see beauty in absolutely everything in life now,” Spill says.

What comes next for dostarlimab

Not only does the immunotherapy appear to work well in treating these rectal cancers, but it also comes with relatively few side effects. About 20% of those in the study reported fatigue, rash, diarrhea, and uncontrollable itching. Roth, who received her infusions during the COVID lockdown, drove from D.C. for her treatments and was able to make the roundtrip in one day. "It's just proof that you can really do the things you want to do. I didn't feel tired or sick after [the treatment], and there was never a time when I was at home recovering," she says. "I watched my mom and dad go through standard chemo and radiation and anticipated that would be what my treatment was like. It was nothing like that."

Cercek says the results point toward a potentially new model for managing some rectal cancers, which may include relying on immunotherapy like dostarlimab and monitoring patients more carefully before automatically turning to chemotherapy, radiation, or surgery. Some of the patients in the trial who were treated on dostarlimab underwent surgery after finishing their infusions if their doctors still felt there might be tumors remaining. Among them, despite the doctors’ suspicions, 80% did not turn out to have evidence of tumors in their specimens, says Cercek.

Dostarlimab is already approved to treat endometrial cancers with the same mutations and costs $10,000 to $12,000 per dose out of pocket, although GSK has a manufacturer's savings program to cover that cost for some patients.

“We still have a lot of learning about what complete clinical response means,” she says, and with immunotherapy, that might mean a more patient-centric, individualized approach that involves more time for the immune system to respond to the immunotherapy and become trained to attack the cancer. “If it looks like the tumor is responding, we need to give it more time with better techniques to determine whether or not the tumor is truly gone.”

Cercek and her team are studying the best ways to monitor how tumors respond to dostarlimab by looking at snippets of genetic information that tumors shed in the blood, or more advanced imaging to accurately capture changing tumor sizes. “We need to improve on those techniques but also to teach the oncology community that there is a very, very high chance that the tumor might disappear, even if it might not look like it at six months. We need to continue watching and waiting and giving it time.”

Wait a second. You’ve been standing in line for 20 minutes, famished and desperate to order one of the viral bagels that keep selling out—or for six hours outside a concert venue, determined to claim a spot at the barricade to see your favorite band.

And then someone strolls up and slips in line ahead of you. Apparently, the rest of you have been standing around for the ambiance.

How much of a sin are line-cutters committing? “You are ripping the fabric of society apart,” says Nick Leighton, an etiquette expert and co-host of the podcast Were You Raised by Wolves? Queue-jumpers have to live with that, he adds. “But worse, we have to live with you.”

Here’s exactly how to handle this maddening situation—including when and how best to speak up.

When to speak up about someone cutting in line

If a stranger jumping ahead of you feels strangely personal, Richard C. Larson, a professor emeritus of data, systems, and society at MIT who has studied queuing, understands why. “We only have a finite number of minutes of life on Earth,” he says. The cutter’s implied message: “A minute of my life is worth more than a minute of yours.”

Before you decide whether to confront the offender, think about what speaking up would accomplish. Are you trying to reclaim your turn or get revenge? Sometimes, the impulse is “to sort of let them know you think they’re a jerk,” says Ryan Martin, a professor of psychology and dean of the College of Arts, Humanities and Social Sciences at the University of Wisconsin–Green Bay, known online as the Anger Professor because he studies strong emotions.

Martin would speak up to help someone recognize “that what they did wasn’t OK and that I wanted them to go to the back of the line,” he says. But he’d also consider: “What is going to allow me to have the kind of night I want to have?” If you spend the concert replaying a confrontation instead of singing your happy heart out, you’ve lost more than your place in line.

Leighton's gut check for situations like these is to ask yourself: Is this the hill you want to die on? “That’s always a good etiquette question,” he says.

Consider your safety, too. If the person seems hostile or you feel uneasy approaching them, you can ask staff for help or let the cut go. “Health and safety always trumps etiquette,” Leighton says.

What to say—if you do decide to say something

Marie Helweg-Larsen, a professor of psychology at Dickinson College who studies social norms, has explored what makes line-cutting so rage-inducing. For a 2008 study, she and a colleague surveyed U2 fans waiting for prime concert-floor spots, asking how they would react to hypothetical line-cutting scenarios.

Interestingly, fans reacted just as negatively to someone cutting behind them as ahead of them—even though their own place wasn’t affected. “You have to have people follow the rules,” she says, “or your investment into the line falls apart.” Helweg-Larsen’s co-author also heard fans invoke a higher authority when someone misbehaved: “Bono wouldn’t like that!” 

You don’t need a rock star’s moral authority—or a grand speech—to point out where the line starts. Helweg-Larsen’s suggested opener: “Excuse me, but the line starts down there.” Aim for an “‘I’m just trying to be helpful’ kind of vibe,” she says.

That approach gives the person a chance to correct their mistake without having to defend their character. And you don’t have to believe it was an innocent oversight to deliver the message graciously. “Even if they’re doing it on purpose, you still need to use that tone,” Leighton says.

He’s been on the receiving end of a polite correction himself: At a deli, he once joined what he thought was the back of the line, only to discover he’d guessed wrong. He was happy for someone to point him in the right direction.

If you decide to speak up, do it promptly. “Your window of opportunity is short,” Leighton says. “As soon as it happens, that’s when you need to say something.” Waiting until you’ve spent five minutes glaring at the back of someone’s head won’t make the conversation any easier.

For a line that represents a serious investment of time, Martin suggests spelling that out: “Hey, I’m not sure you noticed, but there’s actually a really long line here, and people have been waiting all day.” You’ve identified the problem and given them an opening to say “Oops.”

Of course, some situations are murkier than a stranger breezing past the entire queue. Someone returning from a bathroom break is different from four friends arriving hours later to join the person who saved their places. Leighton is sympathetic to a water or restroom run. Holding spots all day for a last-minute entourage? “I don’t love that,” he says.

What to do if a line-cutter won’t move

Sometimes, your kind reminder won’t be met with the same level of helpfulness: They saw the line. They’re staying put. Now what?

If you feel comfortable continuing, Martin suggests a firmer follow-up: “I really think you should go back to the back of the line.” You’re making a direct request without adding an insult.

Larson advises skipping any confrontational nicknames or demands—like “What do you think you’re doing, bud?” You’re pointing someone toward the back of the line, not challenging them to a duel.

If the person still refuses to move, resist the urge to keep arguing. “We can’t control everybody,” Martin says. Continuing to push someone who’s already refused could lead to “a more significant confrontation.”

At a concert venue, amusement park, or other staffed location, you can ask an employee or security person to step in. “You can always appeal to a higher authority,” Leighton says. Whether they’ll enforce the rules is another question, but it’s an option worth trying when the cutting is particularly egregious.

If you decide to drop it, drop the parting shot, too. A sarcastic “Must be nice!” might feel irresistible, but Leighton advises against adding more rudeness to the encounter. “It will not achieve anything,” he says.

As Larson puts it, “A fight can ruin your whole day—or life.”