Colorectal Cancer, Polyps, and Diverticular Disease: Colorectal Cancer and Polyps: Screening to Therapy

0:00Welcome to Board Pearls. This is episode one of two of the Colorectal Cancer, Polyps, and Diverticular Disease chapter, in the Colorectal and Pelvic Floor Disorders module. This episode follows colorectal neoplasia from screening to treatment. A man who doesn't want a colonoscopy shows why screening works, when it starts, what each test catches and misses, and what a positive stool test with a normal colonoscopy means. A woman whose brother had colon cancer shows how family history moves the start. A woman with three kinds of polyp shows why histology decides risk and why the sessile serrated lesion is easy to miss, and a man with many serrated lesions shows when they add up to a syndrome. A woman with a new colon cancer shows the two molecular pathways, Lynch testing on every tumor, and staging. A man with node-positive cancer and a woman with an obstructing tumor show who needs chemotherapy and for how long. A woman with liver metastases shows how the molecular profile and the side of the tumor pick the drugs, and a man with a mismatch repair deficient tumor shows when immunotherapy comes first. And a man and a woman with rectal cancer show why the pelvis changes the approach, with total neoadjuvant therapy, watch-and-wait, and checkpoint therapy before radiation.

1:15Here's the first patient. A forty-six-year-old man comes for a physical. He has no symptoms, no family history of colorectal cancer or polyps, and no inflammatory bowel disease. He's never been screened. He's heard he doesn't need it until fifty, and he doesn't want a colonoscopy.

1:33He's an average-risk adult who has never been screened for colorectal cancer, and why screening works decides which test he should get. Colorectal cancer has a long, recognizable precursor, the adenoma or the serrated lesion, and an early stage that's survivable. So screening does two separate things. It prevents cancer by removing precursors, and it reduces deaths by finding cancer at a curable stage. A test that finds and removes polyps prevents cancer, while a test that mostly detects existing cancer reduces mortality but prevents much less. That's the real difference between colonoscopy and everything else.

2:08What he's heard about fifty is out of date. Average-risk screening starts at forty-five, under the twenty twenty-one United States Preventive Services Task Force recommendation and the twenty eighteen American Cancer Society recommendation. It was lowered from fifty because colorectal cancer is rising in adults under fifty. The multi-society task force, the American College of Gastroenterology, ACG, and the National Comprehensive Cancer Network, NCCN, agree on forty-five, with minor differences in how they rank the tests.

2:40The end of screening is set by life expectancy. Screening continues through seventy-five, is individualized from seventy-six to eighty-five, and generally isn't offered after eighty-five, because the years needed for benefit exceed remaining life expectancy. He's forty-six and due now.

2:57His refusal of colonoscopy doesn't end the conversation, because the range of tests exists so every patient has an acceptable option. Colonoscopy every ten years is preferred, because it detects and removes precancerous lesions in one procedure. Its sensitivity for advanced adenoma approaches ninety-five percent with a good prep and a high-quality endoscopist.

3:16The fecal immunochemical test, FIT, is the most used non-invasive test, and its strength is cancer, not polyps. It's an antibody assay for human hemoglobin in stool. It detects roughly seventy to eighty percent of cancers and is highly specific. But its sensitivity for advanced adenomas is under thirty percent, so it must be repeated every year to build up detection over time. One FIT and stopping isn't meaningful screening.

3:44The multi-target stool deoxyribonucleic acid, DNA, test, every three years, catches more but at a cost. It combines FIT with assays for methylated NDRG4 and BMP3 and mutant KRAS. In its validation cohort it detected about ninety-two percent of cancers and fewer than half of advanced adenomas. Its specificity is lower, around eighty-seven percent, so it produces more false positives, and each one means a colonoscopy.

4:16Computed tomography, CT, colonography every five years avoids sedation but needs the same bowel prep and involves radiation. In five to fifteen percent of patients it finds something outside the colon that prompts more imaging. Flexible sigmoidoscopy every five years, or every ten with yearly FIT, is rarely used in the United States. It covers only the distal colon, and the right colon is where sessile serrated lesions sit, driving a substantial share of interval cancers. Capsule colonoscopy every five years is a third-tier option for selected patients who decline both colonoscopy and stool testing.

4:55The newest option is a blood test, and its weakness is prevention. A methylation cell-free DNA blood test was approved in twenty twenty-four for average-risk screening. It detects about eighty-three percent of cancers, but only about thirteen percent of advanced precancerous lesions, so it prevents almost no cancer. It isn't a first-line test, and it's only for patients who decline colonoscopy and stool testing. The older methylated Septin nine assay performed worse and is mostly historical.

5:24His choice depends on what he objects to. If prep is what he dislikes, CT colonography doesn't spare him that and adds radiation. If sedation is the problem, CT colonography and the stool tests both avoid it. But the stool tests trade away most of the prevention unless a positive result sends him to colonoscopy, where precursors are removed. He chooses the multi-target stool DNA test.

5:49Before the kit is ordered, he has to agree to one thing. Any positive non-invasive test, whether FIT, stool DNA, a blood test, or abnormal CT colonography, is an indication for diagnostic colonoscopy, not a result to repeat. The most common failure in screening is a patient who declines colonoscopy, chooses a stool test, and then declines colonoscopy again after a positive result, which delays detection and gives up prevention. So the commitment to colonoscopy if the test is abnormal is made before he takes the kit home. He agrees.

6:23His stool DNA test is positive. He has a colonoscopy with an excellent prep, cecal intubation, and an experienced endoscopist, and it's completely normal. He asks whether he needs an upper endoscopy or a CT, and he doesn't. In real-world use, about thirty percent of positive stool DNA tests are false positives, mostly never explained by colonoscopy. The multi-society task force states that an asymptomatic patient with a positive stool DNA test and a high-quality negative colonoscopy needs no further gastrointestinal, GI, workup. He returns to routine screening.

7:02The second patient shows how family history moves the clock. A forty-one-year-old woman's brother was diagnosed with colon cancer at forty-eight. A first-degree relative with colorectal cancer or an advanced adenoma at any age moves the start to forty, or ten years before the youngest case, with colonoscopy every five years. Forty and thirty-eight are both behind her, so she's due now.

7:25Some patients start even earlier than that, because their risk isn't from family history alone. The hereditary syndromes, Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis, and Peutz-Jeghers syndrome, start much earlier with much shorter intervals. And colitis from inflammatory bowel disease, IBD, enters dysplasia surveillance eight to ten years after symptom onset, or immediately at the diagnosis of primary sclerosing cholangitis.

7:54The third patient's screening colonoscopy finds polyps, and the question is which ones matter. A fifty-seven-year-old woman has her first screening colonoscopy. In the cecum is a flat, pale, twelve-millimeter lesion covered with a cap of yellow mucus. In the transverse colon is an eighteen-millimeter polyp. In the rectum are three tiny pale polyps, each about three millimeters. All are removed. She asks which she should worry about.

8:20Her three findings carry very different risks, and the microscope, not the scope, tells them apart. Polyps are precursors of two pathways with different molecular drivers and cancer risks. But they can look alike through the scope, especially in the right colon, where a sessile serrated lesion can resemble a harmless hyperplastic polyp. So histology, size, and number decide cancer risk and surveillance.

8:44Her transverse polyp belongs to the conventional pathway, the adenoma-carcinoma sequence. Loss of both copies of APC removes the brake on Wnt signaling and produces a dysplastic adenoma. Activating KRAS mutations drive growth. Then TP53 and SMAD4 are lost, and the advanced adenoma becomes invasive cancer over years to decades. About eighty percent of sporadic colorectal cancer arises this way, with chromosomal instability.

9:13Adenomas are classified by their architecture. Tubular adenomas, with crowded dysplastic glands forming tubes, are the most common. Tubulovillous adenomas have at least twenty-five percent villous architecture. Villous adenomas have more than seventy-five percent, with finger-like fronds and the highest cancer risk.

9:33Size is why large adenomas are removed and not watched. Untreated polyps of a centimeter or more carried a cumulative cancer risk at the polyp site of about two and a half percent at five years, rising to about a quarter at twenty years. The chance that a polyp already contains cancer when it's removed also rises steeply with size and villous histology. It ranges from about one percent for a tubular adenoma under a centimeter to about half of villous adenomas over two centimeters.

10:03Those risks are captured in one definition that drives her surveillance. An advanced adenoma is any one of three features: ten millimeters or more, villous or tubulovillous histology, or high-grade dysplasia, the immediate predecessor of invasive cancer, which makes an adenoma advanced at any size. Her transverse polyp is an eighteen-millimeter tubulovillous adenoma with low-grade dysplasia, advanced on size and histology.

10:30Her cecal and rectal polyps belong to the other pathway, the serrated pathway. It accounts for fifteen to thirty percent of colorectal cancer and was long under-recognized, because its precursor is flat, mucus-capped, and right-sided. It has three members. Hyperplastic polyps are the most common, mostly small and in the rectum and sigmoid, and they're nonpremalignant when diminutive and left-sided. They come in two subtypes, goblet-cell-rich and microvesicular, and the microvesicular kind is thought to precede the sessile serrated lesion. Her three rectal polyps are hyperplastic and don't change her surveillance.

11:07Her cecal lesion is the one that's easy to miss. The sessile serrated lesion is the true serrated precursor. It carries BRAF V600E, the CpG island methylator phenotype, CIMP-high, and MLH1 promoter methylation. Methylation silences MLH1, so the cell can't repair replication errors, and the cancer becomes microsatellite-unstable without any inherited mutation. It's mostly right-sided, flat or slightly raised, and often covered with a mucus cap that may be its most visible feature.

11:38The microscope separates it from a hyperplastic polyp by the crypts. Dilated or distorted basal crypts mark a sessile serrated lesion, while a hyperplastic polyp has straight crypts, and the World Health Organization, WHO, criterion needs only a single unequivocally abnormal crypt. Most have no cytologic dysplasia, and those that develop it are further along toward cancer. Risk concentrates in lesions over ten millimeters and those with dysplasia. Her cecal lesion is a twelve-millimeter sessile serrated lesion without dysplasia.

12:11Because that distinction is hard, a large hyperplastic polyp is treated cautiously. Any hyperplastic polyp of ten millimeters or more is surveyed at three to five years under the twenty twenty multi-society guideline, rather than ten. Pathologists vary in separating it from a sessile serrated lesion, and large right-sided hyperplastic polyps share their molecular features. So a proximal hyperplastic-looking polyp of ten millimeters or more is managed as a sessile serrated lesion.

12:42The third serrated member is rare but always counts. The traditional serrated adenoma has uniform eosinophilic cytologic dysplasia, is often bulky or stalked, is mostly left-sided, and carries KRAS rather than BRAF. It's uniformly dysplastic, so it's treated as an advanced lesion by default.

13:01Her histology now sets her next colonoscopy, under the twenty twenty United States Multi-Society Task Force guideline. One or two small adenomas get seven to ten years. Advanced adenomas and large or dysplastic serrated lesions get three years. More than ten adenomas get one year. With an advanced adenoma and a sessile serrated lesion over ten millimeters, she returns in three years. The polyps to worry about are the cecal and transverse ones, not the three rectal polyps.

13:31The fourth patient shows that serrated lesions can add up to a syndrome. A forty-nine-year-old man has had seven sessile serrated lesions above the rectum across several colonoscopies, three of them over ten millimeters. That's serrated polyposis syndrome. By the twenty nineteen WHO criteria, it's five or more sessile serrated lesions proximal to the rectum with at least two over ten millimeters, or more than twenty serrated polyps of any size with at least five above the rectum. The old family-history criterion was removed.

14:05His count built up across exams, so each report alone looked manageable, and that's how the syndrome is missed. His lifetime colorectal cancer risk is raised, and its genetic basis is mostly undefined. He needs yearly colonoscopy with aggressive clearing.

14:19The fifth patient's colonoscopy finds cancer, not a polyp. A sixty-eight-year-old woman with iron deficiency anemia has a colonoscopy that finds an ulcerated mass in the ascending colon, and the biopsy shows adenocarcinoma. She has no family history of cancer and has never been screened.

14:36She has adenocarcinoma of the ascending colon. Colorectal cancer is the third most common cancer in the United States and the second leading cause of cancer death, with a lifetime risk of about five percent. The tumor's pathway determines treatment, especially in stage four. So before her treatment is planned, her tumor is tested for mismatch repair deficiency, which also screens for Lynch syndrome.

14:59Lynch syndrome is the hereditary form of mismatch repair deficiency, and it looks like the sporadic serrated tumors. It comes from a germline mutation in MLH1, MSH2, MSH6, PMS2, or EPCAM, with right-sided cancers at younger ages that are microsatellite-unstable. About fifteen percent of colorectal cancer is microsatellite-unstable. Roughly twelve to thirteen percentage points of that are sporadic and methylation-driven, and about three are Lynch. Every new colorectal cancer is tested, regardless of family history, because the family-history criteria, Amsterdam and Bethesda, miss too many Lynch patients.

15:43Testing starts with tumor immunohistochemistry for MLH1, MSH2, MSH6, and PMS2, or polymerase chain reaction, PCR, for microsatellite instability. Intact proteins or low instability means sporadic cancer, and the Lynch workup stops. Loss of MSH2, MSH6, or PMS2 alone goes straight to germline testing, because sporadic methylation silences only MLH1.

16:13MLH1 loss needs one more step, because it could be either cause. It usually takes PMS2 with it, because PMS2 is unstable without its partner. It could be Lynch or sporadic methylation, so the tumor is tested for BRAF V600E or MLH1 promoter methylation. Either positive means sporadic, and both negative means germline testing. Her tumor has lost MLH1 and PMS2 and carries BRAF V600E. That's the sporadic serrated pathway, with no implication for her family.

16:47Her treatment depends on her stage, set by the American Joint Committee on Cancer, AJCC, tumor, node, and metastasis, TNM, system. T1 invades the submucosa, T2 the muscularis propria, and T3 goes through the muscularis propria into pericolorectal tissue. T4a perforates the visceral peritoneum, and T4b invades adjacent organs. N0 is no regional nodes, N1 one to three, and N2 four or more. M1a is one distant organ, M1b more than one, and M1c the peritoneum.

17:26The stages group those features. Stage one is T1 or T2 without nodes. Stage two is T3 or T4 without nodes. Stage three is any T with nodes. Stage four is distant spread. At least twelve nodes must be examined for accurate N staging, because too few can miss a positive node and understage the patient.

17:52Her staging workup has three parts, each for a reason. Complete colonoscopy comes first, since a second tumor changes the operation. A baseline carcinoembryonic antigen, CEA, gives a marker to follow after surgery. And CT of the chest, abdomen, and pelvis looks for distant spread. Rectal cancer adds pelvic magnetic resonance imaging, MRI, and metastatic disease may add fluorodeoxyglucose positron emission tomography with CT, FDG-PET/CT, and liver MRI.

18:25Her CT shows no distant spread. After a right hemicolectomy, pathology shows a T3 tumor with none of eighteen nodes involved. That's stage two, T3 N0 M0, with an adequate node count.

18:39Whether she needs chemotherapy follows from that stage. Stage one is surgery alone, a segmental colectomy with regional nodes. Stage two is surgery, with adjuvant chemotherapy only for selected high-risk patients. Stage three is surgery plus mandatory adjuvant chemotherapy, because it improves five-year overall survival by roughly ten to fifteen percent. Stage four is systemic therapy with selective removal of metastases.

19:04A stage two patient's chemotherapy decision rests on high-risk features, because the benefit for stage two overall is small, around two percent, and not statistically robust. The high-risk features are a T4 tumor, perforation or obstruction at presentation, fewer than twelve nodes sampled, lymphovascular invasion, perineural invasion, and poorly differentiated histology. Fewer than twelve nodes is a feature of the specimen, not the tumor, because the patient may really be stage three.

19:35Her mismatch repair result answers her chemotherapy question too. Microsatellite-unstable stage two tumors don't benefit from five-fluorouracil alone and have a favorable prognosis without it. She has no high-risk features, so she's observed. The same mismatch repair test that reassured her family spared her chemotherapy.

19:55The sixth patient shows a stage two cancer that does get chemotherapy. A seventy-one-year-old woman has a stage two, T3 N0 cancer that was obstructing at presentation, with only nine nodes examined. She has two high-risk features, obstruction and an inadequate node count, so she's offered adjuvant chemotherapy.

20:14The seventh patient's cancer has reached his nodes, so chemotherapy isn't optional. A sixty-four-year-old man had a sigmoid colectomy showing a T3 tumor with two of twenty-one nodes involved, no distant spread, and intact mismatch repair proteins. That's stage three, T3 N1, with an adequate node count.

20:32His regimen and its length depend on his risk. The regimens are oxaliplatin-based: FOLFOX, five-fluorouracil, leucovorin, and oxaliplatin, or CAPOX, capecitabine and oxaliplatin, for three to six months. A large international collaboration validated three months of CAPOX for low-risk stage three, T1 to T3 with N1. Six months is still preferred for high-risk stage three, T4 or N2, and for FOLFOX.

21:03Shortening treatment matters because oxaliplatin neuropathy is dose-limiting and cumulative. If it becomes disabling, oxaliplatin stops, and capecitabine or five-fluorouracil with leucovorin continues alone, less effective but with far less neuropathy. He's low-risk stage three and completes three months of CAPOX, with mild fingertip tingling that fades.

21:27After curative resection, his follow-up has three parts, each looking somewhere different. Exam and CEA are done every three to six months for two years, then every six months through year five. CT of the chest, abdomen, and pelvis is done yearly for five years in stage two and three. Colonoscopy is done at one year, then three years later, then five years after that, sooner if the pathology calls for it. CEA and CT look for recurrence outside the colon, and colonoscopy looks for new polyps and second cancers. His CEA and scans stay normal, and his one-year colonoscopy removes a small tubular adenoma.

22:06At the other end of the stages, some T1 cancers need no colectomy at all. A T1 cancer limited to the mucosa or superficial submucosa is cured by endoscopic resection when every favorable feature is present. It must be well or moderately differentiated, with no lymphovascular invasion, no perineural invasion, a deep margin clear by at least one millimeter, and submucosal invasion under one thousand micrometers. Those features predict no nodal spread. Any unfavorable one means colectomy with nodes.

22:40The eighth patient's cancer has spread, and her drugs depend on her tumor's biology. A fifty-eight-year-old woman has a sigmoid cancer with four liver metastases. She's fit and working full time. Her tumor is mismatch repair proficient, KRAS, NRAS, and BRAF wild-type, and HER2 isn't amplified.

23:02She has stage four colon cancer with liver metastases, and her drugs are chosen by reading her tumor profile in a fixed order. Mismatch repair comes first, because deficient, microsatellite-unstable tumors get immunotherapy whatever their RAS status, and proficient tumors get chemotherapy. RAS and BRAF come next, deciding anti-epidermal growth factor receptor, anti-EGFR, therapy and the BRAF regimen. The side of the tumor is a second filter on anti-EGFR therapy. HER2 comes last and opens a later option.

23:36The profile can come from tissue she already has. RAS and BRAF can be tested on the primary or a metastasis, so a liver biopsy isn't needed if primary tissue exists. About forty percent of metastatic colorectal cancers carry KRAS mutations, and NRAS mutations, BRAF V600E, and HER2 amplification are each much less common. Her liver MRI matters because it shows exactly how many metastases there are and where, which a liver surgeon will need.

24:10Her chemotherapy backbone depends on her fitness. Fit patients can get FOLFOXIRI, five-fluorouracil, leucovorin, oxaliplatin, and irinotecan, plus bevacizumab, with the highest response rates and the deepest shrinkage but also the most toxicity. Less-fit patients get a doublet, FOLFOX or FOLFIRI, folinic acid, fluorouracil, and irinotecan, plus bevacizumab. Bevacizumab blocks vascular endothelial growth factor, VEGF, and works regardless of RAS status. It's avoided within four weeks of surgery and with a risk of untreated bowel perforation.

24:48Her RAS result decides whether an anti-EGFR antibody can be added. Cetuximab, a chimeric antibody, and panitumumab, a fully human one, work only when the signaling path beneath EGFR is intact. An activating KRAS or NRAS mutation switches that path on downstream of the receptor, so blocking EGFR does nothing. A BRAF mutation also predicts no response to anti-EGFR drugs alone.

25:18Sidedness is the second filter, because the two sides of the colon are different tumors. Right-sided tumors, cecum to splenic flexure, arise from the midgut. They're more often BRAF-driven and microsatellite-unstable, depend less on EGFR, and don't benefit from anti-EGFR therapy even when RAS is wild-type. Left-sided tumors, descending colon to rectum, arise from the hindgut, follow the conventional sequence, and respond when RAS is wild-type.

25:47Her sigmoid, RAS wild-type tumor passes both filters. She gets chemotherapy plus an anti-EGFR antibody, with liver resection to be considered if her metastases respond. The same RAS result in a cecal tumor would mean chemotherapy with bevacizumab instead. Over six months her liver metastases shrink, and she's referred to a liver surgeon.

26:09Two less common results in the profile have their own treatments. BRAF V600E is a poor-prognosis subtype with its own regimen, encorafenib plus cetuximab, with binimetinib in selected cases. It's more common in right-sided tumors from the serrated pathway, so a right-sided metastatic cancer should prompt a close look at the BRAF result. HER2-amplified tumors respond to HER2-directed therapy after first-line progression, either trastuzumab plus tucatinib or trastuzumab deruxtecan. Getting the full profile at diagnosis means it keeps answering questions in later lines.

26:49The ninth patient shows why mismatch repair is read first. A fifty-four-year-old man has metastatic colon cancer with loss of MLH1 and PMS2, so it's mismatch repair deficient. Pembrolizumab is first-line, ahead of chemotherapy. In a randomized trial in untreated mismatch repair deficient metastatic disease, it nearly doubled progression-free survival compared with chemotherapy, with better tolerability.

27:15His tumor's biology explains why immunotherapy works. Microsatellite-unstable tumors carry a high mutational burden and make abundant neoantigens that T cells recognize. Programmed death one, PD-1, blockade releases the brake on those T cells. Nivolumab plus ipilimumab is an alternative checkpoint regimen, and chemotherapy is kept for mismatch repair proficient tumors.

27:39The tenth patient's cancer is in the rectum, and that changes the approach. A fifty-two-year-old man has had rectal bleeding and narrower stools for three months. Colonoscopy finds a mass eight centimeters from the anal verge, with the rest of the colon clear. The biopsy shows adenocarcinoma with intact mismatch repair proteins. CT shows no distant spread, and his CEA is mildly raised. He asks whether he'll end up with a bag.

28:08He has rectal adenocarcinoma, and whether he ends up with a stoma depends on how the rectum changes treatment. It sits in a fixed pelvis with little room around it, so surgical margins are limited, local recurrence is common, and the circumferential margin matters more than in the colon. So rectal cancer adds neoadjuvant therapy, to shrink the tumor and treat the pelvis before the operation. And it adds total mesorectal excision, removing the rectum with its envelope of fat, the mesorectum, and the nodes inside it.

28:38His local staging requires pelvic MRI, or endoscopic ultrasound when MRI is contraindicated or for early superficial lesions. MRI shows whether tumor or nodes reach the circumferential resection margin and the mesorectal fascia. That decides how much treatment comes before surgery, because an operation through tumor leaves cancer in a pelvis where recurrence is hard to treat.

29:01His MRI shows a T3 tumor with two enlarged mesorectal nodes and a clear mesorectal fascia. T3 or T4, or any node-positive disease, without distant spread, is locally advanced rectal cancer, so surgery doesn't come first.

29:17Early rectal cancers are the exception that can avoid the big operation. A T1 rectal cancer can sometimes be cured by endoscopic resection, using the same favorable features as in the colon. Some early rectal cancers are treated by transanal local excision or endoscopic submucosal dissection rather than total mesorectal excision. Those smaller operations need site surveillance, with flexible sigmoidoscopy or endoscopic ultrasound every three to six months for two to three years, because local recurrence is more common.

29:48His tumor is treated before surgery, and the order of treatment has changed. The traditional approach was chemoradiation or short-course radiation, then total mesorectal excision, then adjuvant chemotherapy based on the pathology. The preferred approach now is total neoadjuvant therapy, TNT, with all chemotherapy and radiation given before surgery, because it raises pathologic complete response rates and allows organ preservation. With all treatment given first, the response is measured with repeat MRI and endoscopy before anyone operates, which is what makes skipping the operation possible.

30:23He completes total neoadjuvant therapy, and repeat MRI and endoscopy show no residual tumor, a complete clinical response. That allows watch-and-wait: no total mesorectal excision for now, close surveillance with endoscopy and MRI, and surgery only if the tumor regrows. The benefit is keeping his rectum, and the cost is intensive surveillance and possible later surgery. He chooses watch-and-wait, and the surveillance is now his treatment plan.

30:50His follow-up combines the colon schedule with the rectal one. Residual tumor after total neoadjuvant therapy, or regrowth during surveillance, means total mesorectal excision. Otherwise his follow-up matches colon cancer, with exam and CEA, yearly CT, and colonoscopy at one, three, and five years, plus the rectal surveillance. His CEA, once normal, becomes a marker for recurrence.

31:16The last patient shows that mismatch repair status changes the rectal sequence too. A forty-seven-year-old woman has locally advanced rectal cancer, T3 with involved nodes, and her tumor has lost MSH2 and MSH6. Mismatch repair deficient locally advanced rectal cancer is now treated upfront with a checkpoint inhibitor. A small but striking trial of dostarlimab produced complete response rates high enough to let patients avoid surgery. So mismatch repair is checked before neoadjuvant therapy is planned, so that pelvic radiation isn't given to a patient who might avoid it.

31:50Her mismatch repair result has a second meaning, for her family. MSH2 and MSH6 loss isn't explained by methylation, so she goes straight to germline testing for Lynch syndrome. If it's positive, her relatives need counseling and testing.

32:04Here are the traps the boards set in these patients. Average-risk screening doesn't wait until fifty, and a healthy eighty-eight-year-old isn't screened. FIT done once isn't screening, because it only works yearly. A positive stool test isn't repeated, and it isn't ordered without a commitment to colonoscopy. A positive stool DNA test with a high-quality negative colonoscopy doesn't need the rest of the GI tract examined. Flexible sigmoidoscopy misses the right colon. A first-degree relative with cancer means starting at forty, not forty-five. And the blood test isn't a first-line option.

32:38The polyp traps follow. A polyp isn't judged by its appearance. A flat, mucus-capped right-sided lesion isn't called hyperplastic. A hyperplastic polyp of ten millimeters or more doesn't get a ten-year interval. And serrated polyposis is missed when the lesions are counted one exam at a time.

32:56The cancer staging and adjuvant traps come next. Lynch testing isn't limited to patients whose family history fits. MLH1 loss isn't called Lynch without BRAF or methylation testing, and BRAF testing isn't run after MSH2 or MSH6 loss. A cancer isn't called node-negative with fewer than twelve nodes. Stage two patients don't all get chemotherapy, and they don't all go without it. A microsatellite-unstable stage two cancer doesn't get five-fluorouracil. Stage three doesn't skip chemotherapy, and the three-month course is for CAPOX in low-risk disease. And a favorable T1 polyp cancer doesn't need a colectomy.

33:35The metastatic and rectal traps close the list. Metastatic chemotherapy isn't started without mismatch repair status. An anti-EGFR drug isn't given for a RAS-mutant or right-sided tumor. BRAF V600E is its own subtype with its own regimen. Bevacizumab isn't given within four weeks of surgery. Locally advanced rectal cancer doesn't go straight to surgery, and it isn't staged without pelvic MRI. A complete clinical response isn't operated on without discussing watch-and-wait. And chemoradiation isn't started before mismatch repair is checked.

34:10So, start to finish. Screening prevents cancer by removing precursors and reduces deaths by finding early cancer. Average-risk screening runs from forty-five to seventy-five, and a first-degree relative moves it to forty or ten years before the youngest case, every five years.

34:28Colonoscopy every ten years finds and removes precursors. FIT works only yearly. Stool DNA every three years catches more but gives more false positives. Any positive non-invasive test needs colonoscopy.

34:42Classify polyps by histology. Advanced adenomas are ten millimeters or more, villous, or high-grade dysplasia. Sessile serrated lesions are flat, right-sided, mucus-capped, and BRAF-mutant, and large proximal hyperplastic polyps are managed like them.

34:58Test every new cancer for mismatch repair. MSH2, MSH6, or isolated PMS2 loss goes to germline testing, and MLH1 loss goes first to BRAF or methylation testing. Stage with TNM and at least twelve nodes.

35:15Stage three gets oxaliplatin chemotherapy, three months of CAPOX for low risk and six months for high risk. Stage two gets it only with high-risk features, and never for microsatellite-unstable tumors.

35:29In metastatic disease, mismatch repair deficient tumors get pembrolizumab first. Proficient tumors get chemotherapy with bevacizumab, or with an anti-EGFR antibody only if RAS wild-type and left-sided. BRAF V600E gets encorafenib with cetuximab.

35:49Rectal cancer needs pelvic MRI and total neoadjuvant therapy for locally advanced disease, with watch-and-wait after a complete clinical response and a checkpoint inhibitor first for mismatch repair deficient tumors.

36:02Episode two, the last of the chapter, is diverticular disease: who needs antibiotics, when an abscess needs a drain, who needs surgery, and a colitis that spares the rectum.

36:13For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of two of chapter fifteen, and I'll see you in the next one.