Colon Cancer Landmark Atlas

What did the researchers want to learn?

In colon cancer removed by surgery, does adding oxaliplatin to classic fluorouracil treatment reduce the chance of the disease coming back?

What did this study change?

Adjuvant (postoperative) FOLFOX and other oxaliplatin-containing regimens became the foundation of standard postoperative options in suitable colon cancer.

Benefit for patients

It concerns the postoperative treatment decision aimed at reducing recurrence risk in resected colon cancer, especially stage III.

What did the research find?

In stage III and selected high-risk patients, adding oxaliplatin lengthened the time without recurrence. The survival benefit is read separately by stage and by time point; not every early-stage patient needs the same regimen.

Who does this apply to?

Applies particularly to stage III and to selected high-risk stage II disease. In older, frail patients or those at high risk of neuropathy, duration and dose are individualized. It is not automatically applied to rectal cancer.

What did the researchers want to learn?

Does adding the drug oxaliplatin to standard chemotherapy given after surgery lengthen the time before the disease comes back?

What did this study change?

It supported the view that oxaliplatin can contribute to reducing the risk of recurrence in postoperative treatment. This benefit did not translate into a proven increase in overall survival.

Benefit for patients

It concerns colon cancer patients considered for postoperative oxaliplatin-containing chemotherapy.

What did the research find?

Five years later, the proportion of patients alive without recurrence was 69.4% in the oxaliplatin group and 64.2% in the control group. Five-year overall survival rates were 80.2% and 78.4%; in the updated analysis the difference in overall survival was not statistically significant.

Who does this apply to?

The FLOX regimen used in the study is not the same as the FOLFOX and CAPOX regimens commonly used today. Side effects and differences in administration are assessed separately for each person.

What did the researchers want to learn?

In some patients, may 3 months of oxaliplatin-based chemotherapy after surgery be enough, or are 6 months needed?

What did this study change?

A shorter adjuvant duration became a topic of discussion in selected patients in order to reduce the risk of neuropathy.

Benefit for patients

It concerns patients for whom the balance between postoperative chemotherapy duration and neuropathy risk in stage III colon cancer is being considered.

What did the research find?

In selected low-risk patients, 3 months of treatment may give results close to 6 months, whereas in high-risk disease 6 months may appear safer. The decision on duration varies by risk group.

Who does this apply to?

Risk group (T and N features) is critical. It is not correct to say 3 months for all patients.

What did the researchers want to learn?

In high-risk stage II and stage III colorectal (colon and rectal) cancer, is giving postoperative chemotherapy for three months as safe and effective as giving it for six months?

What did this study change?

In decisions about treatment duration, not only the risk of recurrence but also lasting nerve side effects and quality of life can now be taken into account.

Benefit for patients

It concerns the adjuvant duration decision in high-risk stage II and stage III colon or rectal cancer.

What did the research find?

Three years later, the proportion of patients alive without recurrence was 76.7% with three months of treatment and 77.1% with six months; the study's prespecified non-inferiority criterion (that the shorter treatment was not worse) was met. In the subgroup with safety data, moderate or worse nerve damage (numbness, tingling) was reported in 58% with six months of treatment and 25% with three months.

Who does this apply to?

The study covers not only colon cancer but also rectal cancer. The drug regimen and risk group are important; this study is one of the datasets evaluated together with other studies addressing the same question and should not be read as a completely independent second piece of evidence.

What did the researchers want to learn?

In stage II colon cancer, can making the chemotherapy decision by looking at circulating tumor DNA in the blood reduce unnecessary chemotherapy while maintaining control of recurrence?

What did this study change?

It showed that tests for residual disease in the blood may help personalize the need for chemotherapy in some patients. It cannot yet be said to have become the standard decision method for everyone in every center.

Benefit for patients

It concerns patients in whom whether postoperative chemotherapy is needed in stage II colon cancer is being discussed.

What did the research find?

Use of postoperative chemotherapy was 15% in the blood-test-guided group and 28% in the standard group. Two years later, the proportion of patients alive without recurrence was 93.5% and 92.4%, respectively; the study's prespecified non-inferiority criterion for the guided approach (that it was not worse) was met.

Who does this apply to?

Even when the test result is negative, it cannot be said with certainty that no microscopic cancer cells remain. The test method, the timing of the blood draw and long-term results are important; the findings apply only to stage II patients.

What did the researchers want to learn?

In locally advanced colon cancer with mismatch repair deficiency (dMMR), does giving nivolumab and ipilimumab before surgery produce a strong response in the tumor?

What did this study change?

It is important data showing that immunotherapy before surgery can produce a very high tumor response in dMMR colon cancer. Longer follow-up and comparative studies are needed for it to become established as a standard approach.

Benefit for patients

It concerns patients with dMMR/MSI-H features and planned surgery for colon cancer.

What did the research find?

In the tissue removed at surgery, regression of most of the tumor was reported in 98%, marked regression in 95%, and complete disappearance of the tumor (pathological complete response, pCR) in 68%. In the published analysis, no recurrence of the disease was observed at a median follow-up of 26 months.

Who does this apply to?

There is no comparison (control) group. Complete disappearance of the tumor at surgery is not a guarantee of lasting cure, and this study does not show that surgery can be safely omitted. It applies only to colon cancer with mismatch repair deficiency (dMMR).

What did the researchers want to learn?

In colorectal cancer that is microsatellite instability-high or has mismatch repair deficiency (MSI-H/dMMR) and has not previously been treated with drugs for metastatic disease, does pembrolizumab give better results than standard chemotherapy?

What did this study change?

It became one of the key studies that established first-line immunotherapy in MSI-H/dMMR metastatic colorectal cancer.

Benefit for patients

It concerns patients with microsatellite-unstable or dMMR metastatic colorectal cancer.

What did the research find?

Median progression-free survival (time before the disease progressed) was 16.5 months with pembrolizumab and 8.2 months with chemotherapy. At five years of follow-up, median overall survival was reported as 77.5 and 36.7 months; because a significant proportion of patients in the chemotherapy group later received immunotherapy, the survival results should be interpreted in this context.

Who does this apply to?

The findings cannot be applied to all patients with metastatic colorectal cancer; the biomarker microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) is required. The study covers tumors of both colon and rectal origin together.

What did the researchers want to learn?

In operated stage III colon cancer with mismatch repair deficiency (dMMR), does adding atezolizumab to postoperative FOLFOX chemotherapy lengthen the time before the disease comes back (disease-free survival)?

What did this study change?

It showed a disease-free survival benefit from adding immunotherapy after surgery in stage III dMMR colon cancer. With FDA approval — 8 October 2026 (United States), an approved adjuvant option now exists for this indication. Licensing / reimbursement in Turkey is separate.

Benefit for patients

It concerns patients with surgically treated stage III dMMR colon cancer.

What did the research find?

At a median follow-up of about 41 months, the proportion of patients alive without recurrence at three years was 86.3% in the combination group and 76.2% in the control group (absolute difference about 10 percentage points; hazard ratio 0.50; p<0.001). This hazard ratio is a relative event rate; it does not mean a 50% reduction in absolute risk. Severe side effects (grade 3–4) occurred in 84.1% of the combination group and 71.9% of the control group. The difference in overall survival (total survival time) is not yet clear.

Who does this apply to?

Valid only for stage III colon cancer with mismatch repair deficiency (dMMR). Overall survival data are not yet mature; the increase in side effects should be monitored. FDA approval applies to the United States; it is not automatically considered standard in Turkey and other countries.

What did the researchers want to learn?

In locally advanced colon cancer that can be operated on, is it beneficial to give part of the chemotherapy before surgery?

What did this study change?

It supported preoperative chemotherapy as an option in selected locally advanced colon cancers.

Benefit for patients

It concerns selected patients with resectable, locally advanced colon cancer.

What did the research find?

The rate of residual or recurrent disease within two years was 16.9% in the preoperative chemotherapy group and 21.5% in the control group (p=0.037). The rate of complete surgical removal of the tumor was about 94% vs 89%.

Who does this apply to?

Staging by computed tomography may make the disease appear more advanced than it is. In tumors with mismatch repair deficiency (dMMR), the benefit of this chemotherapy has appeared more limited; postponing surgery in patients at risk of bowel obstruction is assessed separately.

What did the researchers want to learn?

In metastatic colorectal cancer with mismatch repair deficiency (dMMR) / microsatellite instability-high (MSI-H), is nivolumab effective alone or together with ipilimumab?

What did this study change?

It contributed to the development of immunotherapy strategies in dMMR/MSI-H metastatic colorectal cancer; it is not randomized evidence that on its own changed the standard.

Benefit for patients

It concerns patients with MSI-H or dMMR metastatic colorectal cancer.

What did the research find?

Clinically meaningful responses, and long-lasting responses in some patients, were shown with nivolumab-based treatments. The different patient groups (cohorts) were not compared directly with each other.

Who does this apply to?

Superiority cannot be inferred by comparing cohorts with each other. Tumors of colon and rectal origin may be included together. The level of evidence is not the same as that of KEYNOTE-177, a randomized phase III study.

What did the researchers want to learn?

In high-risk locally advanced colon cancer, does giving FOLFOX chemotherapy before surgery increase tumor regression?

What did this study change?

Before the FOxTROT study, it provided early evidence that preoperative chemotherapy is feasible; on its own it did not change the standard.

Benefit for patients

It concerns selected patients with locally advanced colon cancer.

What did the research find?

Tumor regression was seen in the group receiving FOLFOX before surgery. The study was not designed to prove a survival advantage.

Who does this apply to?

Because of the small number of patients, the early-phase (phase II) design and limited statistical power for survival, no conclusions can be drawn about survival time.

What did the researchers want to learn?

In operated early-stage colorectal cancer in which the need for additional chemotherapy is uncertain, does fluorouracil-based chemotherapy provide a benefit?

What did this study change?

It supported the view that in stage II patients the chemotherapy decision should be made individually, weighing the expected small benefit against side effects.

Benefit for patients

It concerns patients in whom the chemotherapy decision after resected stage II colon cancer is being discussed.

What did the research find?

Postoperative chemotherapy showed a modest reduction in the risk of recurrence and death. The absolute benefit is limited and is weighed together with side effects.

Who does this apply to?

A large part of the study was conducted before today's molecular classification and modern chemotherapy regimens; it covers colon and rectal cancer together. It cannot be applied one-to-one to a patient today.

What did the researchers want to learn?

In stage III colon cancer, does adding the drug celecoxib to standard postoperative chemotherapy lengthen the time before the disease comes back?

What did this study change?

It did not support routinely adding celecoxib to postoperative chemotherapy; negative studies are also valuable in showing what should not be done in practice.

Benefit for patients

It concerns the discussion of additional drugs in colon cancer patients receiving postoperative FOLFOX.

What did the research find?

In the overall patient group, adding celecoxib did not show a significant advantage in the time before the disease came back; that is, the main goal of the study was not met.

Who does this apply to?

Additional analyses in specific molecular subgroups cannot be generalized as a treatment recommendation for all patients.