Rectal Cancer Landmark Atlas

What did the researchers want to learn?

In locally advanced rectal cancer, does completing chemotherapy before surgery after short-course radiotherapy reduce disease-related treatment failure compared with classic long-course chemoradiotherapy?

What did this study change?

In selected high-risk rectal cancer, options for intensive systemic treatment before surgery (total neoadjuvant therapy, TNT) were strengthened.

Benefit for patients

It concerns the sequence of preoperative treatment in suitable patients with locally advanced rectal cancer.

What did the research find?

In high-risk locally advanced disease, the RAPIDO approach reduced disease-related treatment failure. This does not mean the same plan for every rectal cancer; organ preservation and other TNT schedules are separate studies.

Who does this apply to?

Designed for high-risk locally advanced rectal cancer. It is not automatically generalized to early-stage or low-risk disease, or to patients whose only goal is organ preservation. The overall survival advantage is not the same in every analysis.

What did the researchers want to learn?

In locally advanced rectal cancer, does adding intensive chemotherapy (mFOLFIRINOX) induction treatment to preoperative radiotherapy and chemotherapy improve long-term outcomes?

What did this study change?

In suitable patients who can tolerate intensive chemotherapy, it supports the long-term benefit of an approach in which all treatments are given before surgery.

Benefit for patients

It concerns patients with locally advanced, resectable rectal cancer.

What did the research find?

At seven years of follow-up, the proportions of patients alive without recurrence and alive overall were reported to be higher in the intensive chemotherapy arm than in the control arm. These two measures cannot be used in place of each other; both were reported separately.

Who does this apply to?

The side effects of intensive chemotherapy and patient selection must be evaluated carefully; it is not suitable for every rectal cancer patient.

What did the researchers want to learn?

In selected rectal cancer patients with a complete response, is close surveillance possible instead of surgery?

What did this study change?

In selected patients, watch-and-wait became something discussed within multidisciplinary protocols.

Benefit for patients

It concerns selected rectal cancer patients with clinical complete response after preoperative treatment.

What did the research find?

In suitable patients with a complete response, an organ-preservation strategy became stronger as a feasible option in selected centers. A path without surgery is not available for every patient.

Who does this apply to?

Close-surveillance infrastructure, an experienced center and patient adherence are essential. In partial response or suspicious disease, the surgical plan is maintained.

What did the researchers want to learn?

In selected rectal cancer patients who are not at high risk, does giving FOLFOX chemotherapy before surgery and using radiotherapy only when needed fall short of routine chemoradiotherapy in terms of the time before the disease comes back?

What did this study change?

It showed that in a suitably selected group of patients, routine use of radiotherapy can be reduced.

Benefit for patients

It concerns patients with locally advanced rectal cancer in a defined risk group.

What did the research find?

At five years, in terms of time before the disease came back, the approach using radiotherapy sparingly was not worse than routine chemoradiotherapy (the non-inferiority criterion was met).

Who does this apply to?

The results cannot be generalized to all high-risk locally advanced rectal cancers; the eligibility criteria in the protocol are important.

What did the researchers want to learn?

In total preoperative treatment, how does giving chemotherapy before versus after chemoradiotherapy affect tumor response and long-term outcomes?

What did this study change?

If organ preservation is the priority, it strengthened the rationale for preferring the sequence of chemoradiotherapy followed by consolidation chemotherapy; the time before the disease came back was equivalent.

Benefit for patients

It concerns patients undergoing neoadjuvant planning for locally advanced rectal cancer.

What did the research find?

The rate of complete disappearance of the tumor at surgery was about 25% (chemoradiotherapy first, then chemotherapy) and 17% (chemotherapy first, then chemoradiotherapy). The time before the disease came back at three years was about 73% in both arms; that is, the difference in response did not translate into a difference in survival / disease-free time.

Who does this apply to?

It is a phase II pick-the-winner design. Complete disappearance of the tumor is not the same thing as the time before the disease comes back.

What did the researchers want to learn?

Can an approach containing short-course radiotherapy and chemotherapy be a suitable alternative to long-course chemoradiotherapy?

What did this study change?

It supported considering short-course radiotherapy plus chemotherapy as an alternative to long-course chemoradiotherapy in selected patients.

Benefit for patients

It concerns patients with locally advanced rectal cancer.

What did the research find?

At three years, the time before the disease came back was about 64.5% (short-course radiotherapy plus chemotherapy) and 62.3% (long-course chemoradiotherapy); the short approach was not worse. Three-year survival rates were about 86.5% and 75.1%. Serious side effects before surgery were more frequent in the short-course plus chemotherapy arm.

Who does this apply to?

The study population and the postoperative drug plan differ between the arms; long-term follow-up is ongoing.

What did the researchers want to learn?

In locally advanced, high-risk rectal cancer, can chemotherapy following short-course radiotherapy be an alternative to long-course chemoradiotherapy?

What did this study change?

It laid the groundwork for today's total preoperative treatment studies; it is not identical to current protocols.

Benefit for patients

It concerns rectal cancer patients planned for preoperative radiotherapy.

What did the research find?

The clear (R0) surgical margin rate was about 77% and 71%; the difference was not significant. Early on, three-year survival appeared higher in the short-course radiotherapy arm, but by eight years it had equalized at about 49% in both arms.

Who does this apply to?

Conducted for fixed / advanced tumors. The early survival difference disappeared in the long term; the R0 difference was also not significant.

What did the researchers want to learn?

In selected small low rectal tumors that respond well to chemoradiotherapy, can removing only the area where the tumor is located (local excision) be an alternative to the standard operation in which the whole rectum is removed?

What did this study change?

It showed that local excision may have a place in the organ-preservation approach; it does not mean that it replaces the standard operation in all T2–T3 rectal cancers.

Benefit for patients

It concerns the local treatment decision in selected rectal cancer patients.

What did the research find?

In the selected patient group, the rate of the tumor coming back in the same area was reported as about 7% in both groups.

Who does this apply to?

Applies to very carefully selected patients; in the local excision group, some patients additionally needed the standard operation.

What did the researchers want to learn?

Is it possible to personalize treatment by looking at the MRI response to chemotherapy before surgery?

What did this study change?

It strengthened the clinical framework for the idea of intensifying or adapting treatment according to MRI response; it cannot be said to have become a standard practice.

Benefit for patients

It concerns patients with locally advanced rectal cancer.

What did the research find?

After four cycles of intensive chemotherapy, about 15 of every hundred patients were considered 'good responders'. The clear surgical margin (R0) rate was 100% in the good-response arms; in poor responders it was about 83% in the standard chemoradiotherapy arm and 88% in the intensified arm. The number of patients in the good-response arms is very small.

Who does this apply to?

Accrual in the good-response arms is low; the results are not generalized to all locally advanced rectal cancer.

What did the researchers want to learn?

In selected early and intermediate-stage rectal cancer, can an approach that preserves the rectum according to the response to treatment reduce the need for the operation in which the whole rectum is removed?

What did this study change?

It is a current and important study in terms of response-based organ preservation; it has not yet changed standard practice.

Benefit for patients

It concerns selected early-stage rectal cancer patients.

What did the research find?

In patients who preferred organ preservation, the rate of avoiding removal of the rectum at 12 months was reported as 78.5% in the long-course chemoradiotherapy arm and 60.6% in the short-course radiotherapy arm. These are early interim results.

Who does this apply to?

Definite equivalence or superiority should not be stated until longer-term results and cancer-safety assessments are completed. It applies only to selected patients.

What did the researchers want to learn?

In locally advanced rectal cancer with mismatch repair deficiency (dMMR), can dostarlimab (a PD-1 inhibitor immunotherapy) given before surgery make the tumor disappear completely on examination and imaging?

What did this study change?

It created a pioneering paradigm signal for a biomarker (dMMR)-based, non-operative organ-preservation approach. AZUR-1 is cross-linked as confirmatory / supporting evidence; it is not a second star.

Benefit for patients

It concerns patients with dMMR/MSI-H locally advanced rectal cancer.

What did the research find?

In all of the first 12 patients who completed treatment, complete disappearance of the tumor on examination and imaging (clinical complete response) was reported.

Who does this apply to?

In the first report the number of patients is very small and follow-up is limited; the results cannot be generalized to all rectal cancer patients. Valid only for patients with mismatch repair deficiency (dMMR).

What did the researchers want to learn?

In rectal cancer with mismatch repair deficiency (dMMR), do the strong responses first observed continue in a larger patient group?

What did this study change?

It strengthened the potential for non-operative organ preservation; it is an expanded extension of the MSK pioneering registry — it is not an independent gold star.

Benefit for patients

It concerns patients with dMMR locally advanced rectal cancer.

What did the research find?

A clinical complete response was reported in all 41 patients who completed treatment (ASCO 2024 update). A complete response lasting at least 12 months has been reported in 20 patients. The first NEJM 2022 report was 12/12. These rates are not the same as the independently assessed rate in AZUR-1.

Who does this apply to?

Single-arm study; only for disease with mismatch repair deficiency (dMMR). It is a congress update; long-term and multicenter confirmation is read together with AZUR-1.

What did the researchers want to learn?

In stage II–III locally advanced rectal cancer with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status, can a lasting clinical complete response be achieved with dostarlimab?

What did this study change?

International confirmatory AZUR-1 data and FDA accelerated approval (United States) support the MSK pioneering cohort. It is not an independent gold star — it is a clinical milestone.

Benefit for patients

It concerns patients with dMMR rectal cancer.

What did the research find?

The US drug authority (FDA) granted accelerated approval to dostarlimab for this use on 19 October 2026. On independent central review, the 12-month clinical complete response was about 47% (116 patients); on investigator assessment, about 68% was reported. These two rates are not the same thing. In addition, there are patients with a complete response who have been followed for less than 12 months; close follow-up is needed.

Who does this apply to?

Single-arm design. Accelerated approval is not lasting cure. FDA confirmation: study completion target October 2029; final report July 2030. Licensing in Turkey is separate. Valid only for disease with dMMR or MSI-H (microsatellite instability-high) status.

What did the researchers want to learn?

In locally advanced rectal cancer, does giving chemoradiotherapy before surgery or after surgery lead to better outcomes?

What did this study change?

It formed the basis for preoperative chemoradiotherapy becoming standard.

Benefit for patients

It concerns patients with locally advanced rectal cancer.

What did the research find?

Five-year local recurrence was about 6% (before surgery) and 13% (after surgery); survival was similar (Sauer NEJM 2004). That is, the benefit in local control stood out; this does not mean survival was prolonged.

Who does this apply to?

Today's MRI staging, surgical quality and drug treatments differ from those in the study era; the results cannot be applied one-to-one to a patient today.

What did the researchers want to learn?

Does short-course radiotherapy before surgery reduce the tumor coming back in the same area compared with a selective postoperative chemoradiotherapy approach?

What did this study change?

It strengthened the place of short-course preoperative radiotherapy in local control.

Benefit for patients

It concerns patients for whom radiotherapy timing in rectal cancer is being discussed.

What did the research find?

Three-year local recurrence was about 4.4% (short-course radiotherapy before surgery) and 10.6% (selective postoperative chemoradiotherapy) (Lancet 2009). Local recurrence is not the same thing as survival.

Who does this apply to?

Conducted in a context before modern staging and total neoadjuvant treatment.

What did the researchers want to learn?

Does adding short-course radiotherapy before surgery to standardized rectal excision surgery (TME, total mesorectal excision) reduce the tumor coming back in the same area?

What did this study change?

It became one of the cornerstones of the discussion of high-quality standard surgery together with short-course radiotherapy.

Benefit for patients

It concerns patients with resectable rectal cancer.

What did the research find?

Two-year local recurrence was about 2.4% (short-course radiotherapy plus standard surgery) and 8.2% (standard surgery alone) (NEJM 2001). It showed that surgical quality and radiotherapy need to be evaluated together.

Who does this apply to?

Long-term side effects and bowel function outcomes must also be evaluated. Modern staging and treatments differ from those in the study era.

What did the researchers want to learn?

In rectal cancer, is laparoscopic (keyhole) surgery comparable with open surgery in terms of cancer outcomes?

What did this study change?

It supported the view that the laparoscopic approach can be an option in terms of cancer outcomes in experienced centers.

Benefit for patients

It concerns rectal cancer patients for whom surgical approach is being chosen.

What did the research find?

Three-year locoregional recurrence was about 5% in both arms (NEJM 2015). It is one of the pieces of evidence for the oncologic safety of the keyhole method in experienced centers; it is not a claim of survival superiority.

Who does this apply to?

The surgeon's experience, patient selection and long-term results are important.

What did the researchers want to learn?

Is laparoscopic (keyhole) rectal cancer surgery equivalent to open surgery in terms of the quality of the tissue removed?

What did this study change?

It showed that the quality of tissue removed by keyhole surgery needs to be evaluated carefully and that this measure needs to be interpreted separately.

Benefit for patients

It concerns the rectal cancer surgical approach decision.

What did the research find?

On early pathology measures, it could not be shown that laparoscopy was not worse than open surgery; that is, the main goal of the study was not met. This does not mean that the keyhole method is worse in every patient.

Who does this apply to?

Conducted for selected surgeons and selected patients; the failure to demonstrate equivalence does not mean laparoscopy is worse in every patient.

What did the researchers want to learn?

Is laparoscopic rectal cancer surgery equivalent to open surgery in terms of the quality of the tissue removed?

What did this study change?

It allowed the quality of tissue from keyhole surgery to be read as separate evidence and emphasized careful patient and surgeon selection.

Benefit for patients

It concerns candidates for minimally invasive rectal cancer surgery.

What did the research find?

Similar to the ALaCaRT study, on early pathology measures it could not be shown that laparoscopy was not worse than open surgery; that is, the main goal of the study was not met.

Who does this apply to?

The failure to demonstrate equivalence does not mean laparoscopy is worse in every patient. The two studies addressing the same question are presented on the page as separate cards.

What did the researchers want to learn?

Does robot-assisted rectal surgery reduce the need to convert to open surgery during the operation compared with laparoscopic surgery?

What did this study change?

It was a reminder that conversion to open surgery, cancer outcomes and bowel / urinary function outcomes need to be read together; it did not prove the superiority of robotic surgery.

Benefit for patients

It concerns patients considering robotic surgery for rectal cancer.

What did the research find?

Conversion to open surgery was about 8.1% (robotic) and 12.2% (laparoscopic); the difference was not statistically significant (JAMA 2017). Conversion rate is not survival or local recurrence superiority.

Who does this apply to?

The surgeon's experience, the learning curve, cost and the change of technology over time are important.