Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Multicenter Retrospective Study.

Background: A proportion of rectal cancer patients who achieve a clinical complete response may develop local regrowth. Although salvage appears to provide appropriate local control, the risk of distant metastases is less known.

Objective: To compare the risk of distant metastases between patients who achieve a clinical complete response (watch-and-wait strategy) and subsequent local regrowth and patients managed by surgery after chemoradiation.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

Background: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients.

Watch and Wait Approach for Rectal Cancer.

The administration of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorrectal excision (TME) and selective use of adjuvant chemotherapy can still be considered the standard of care in locally advanced rectal cancer (LARC). However, avoiding sequelae of TME and entering a narrow follow-up program of watch and wait (W&W), in select cases that achieve a comparable clinical complete response (cCR) to nCRT, is now very attractive to both patients and clinicians. Many advances based on well-designed studies and long-term data coming from big multicenter cohorts have drawn some important conclusions and warnings regarding this strategy.

The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database.

Background: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases.

Objective: This study aimed to investigate risk factors for distant metastases using time-dependent analyses.

Watch and wait: Why, to whom and how.

The current standard of care for the treatment of locally advanced rectal cancer includes neoadjuvant chemoradiation (nCRT) followed by total mesorrectal excision (TME). The observation of significant primary tumor response to radiation and chemotherapy led to the idea of organ-preserving strategies in selected patients who achieved clinical, endoscopic and radiological evidence of complete tumor regression. One of these strategies includes no immediate surgery with close surveillance, known as the Watch and Wait strategy (W&W).

Nonoperative Management of Rectal Cancer: The Watch and Wait Strategy.

In recent decades, rectal cancer management has become increasingly challenging for multiple reasons. Proper imaging using dedicated magnetic resonance, standardization of total mesorectal excision, and incorporation of neoadjuvant treatment regimens have contributed to a significant decrease in local recurrence rates. The observation of complete tumor response to radiation or chemoradiation led to the proposal of organ-preservation strategies with avoidance of immediate surgery and close surveillance (Watch and Wait strategy) in selected patients.

The "Immunoscore" in rectal cancer: could we search quality beyond quantity of life?

Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit.

Watch and wait after a clinical complete response in rectal cancer patients younger than 50 years.

Background: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk.

Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study.

Background: Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up.

Nonoperative Management for T2 Low Rectal Cancer: A Western Approach.

The possibility of organ preservation in early rectal cancer has gained popularity during recent years. Patients with early tumor stage and low risk for local recurrence do not usually require neoadjuvant chemoradiation for oncological reasons. However, these patients may be considered for chemoradiation exclusively for the purpose of achieving a complete clinical response and avoid total mesorectal excision.

Salvage Surgery With Organ Preservation for Patients With Local Regrowth After Watch and Wait: Is It Still Possible?

Background: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision.

A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy.

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (IS) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait").

Experimental Design: Biopsies from two independent cohorts ( = 131, = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3 and CD8 T cells and quantified by digital pathology to determine IS.

Controversies in Rectal Cancer Treatment and Management.

Incorporation of new treatment modalities has significantly increased the complexity of the treatment and management of rectal cancer, including perioperative therapy for local advanced disease and organ preservation for those with response to the preoperative treatment. This review may help practitioners better understand the rationale and selection.

Prediction of Poor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer Using a DNA Repair Deregulation Score: Picking the Losers Instead of the Winners.

Background: Patients with rectal cancer may undergo neoadjuvant chemoradiation even in early stages in an attempt to achieve complete clinical response and undergo organ preservation. However, prediction of tumor response is unavailable. In this setting, accurate identification of poor responders could spare patients with early stage disease from potentially unnecessary chemoradiation.

Microscopic intramural extension of rectal cancer after neoadjuvant chemoradiation: A meta-analysis based on individual patient data.

Objective: In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT.

The Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer-The Impact in Intratumoral Heterogeneity.

Intratumoral genetic heterogeneity (ITGH) is a common feature of solid tumors. However, little is known about the effect of neoadjuvant chemoradiation (nCRT) in ITGH of rectal tumors that exhibit poor response to nCRT. Here, we examined the impact of nCRT in the mutational profile and ITGH of rectal tumors and its adjacent irradiated normal mucosa in the setting of incomplete response to nCRT.

Achieving a Complete Clinical Response After Neoadjuvant Chemoradiation That Does Not Require Surgical Resection: It May Take Longer Than You Think!

Background: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed by organ-preserving strategies and acceptable long-term outcomes. Controversy still exists regarding optimal timing for the assessment of tumor response after neoadjuvant chemoradiation.

Objective: The purpose of this study was to estimate the time interval for achieving complete clinical response using strict endoscopic and clinical criteria after a single neoadjuvant chemoradiation regimen.

Conditional Survival in Patients With Rectal Cancer and Complete Clinical Response Managed by Watch and Wait After Chemoradiation: Recurrence Risk Over Time.

Objective: Analyze conditional recurrence-free survival (cRFS) for rectal cancer patients with complete clinical response (cCR) after neoadjuvant chemoradiation (nCRT) managed nonoperatively after each year without recurrence.

Summary Background Data: Select patients with cCR after nCRT have been managed nonoperatively. Risk factors for local recurrence, the need for prolonged follow-up, and the risk of recurrence over time are not well defined.