The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer.

Neoadjuvant systemic therapy has many potential advantages over up-front surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. Due to these advantages, neoadjuvant therapy is becoming the standard of care for an increasing number of tumor types. Currently, colon cancer patients are still routinely treated with up-front surgery, and neoadjuvant systemic therapy is not yet standard. Limitations to widespread use of neoadjuvant therapy have included inaccurate radiological staging, concerns about tumor progression while undergoing preoperative treatment rendering a patient incurable, and a lack of randomized data demonstrating benefit. However, there is great interest in neoadjuvant chemotherapy, and a number of trials are under way. Early follow up of the first phase III trial of neoadjuvant chemotherapy for colon cancer demonstrated tumor downstaging and suggested an improvement in disease-free survival with neoadjuvant chemotherapy, and it is hoped that this will translate into longer-term overall survival benefit. Clinicians should closely watch this developing field, consider the option of neoadjuvant chemotherapy for colon cancer patients, and actively seek out opportunities for their patients to participate in ongoing clinical trials to further inform this field in future.

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.

An update on the use of immunotherapy in patients with colorectal cancer.

Introduction: Colorectal cancer (CRC) is the third most common malignancy worldwide, with recent trends demonstrating increasing incidence amongst younger patients. Despite multiple treatment options, metastatic disease remains incurable. A new therapeutic strategy to harness the host immune system, specifically with immune checkpoint inhibitors, now has reported results from a number of clinical trials. Areas covered: This review will discuss in detail microsatellite instability (MSI) and other biomarkers for response to immunotherapy, summarize the pivotal clinical trials of immune checkpoint inhibitors in early-stage and metastatic MSI colorectal cancer, explore strategies to induce treatment responses in MSS CRC and highlight the emerging treatments and novel immune-based therapies under investigation. Expert opinion: Immunotherapy is now a standard of care for the proportion of CRC patients with MSI. While overall survival data are still awaited, the promise of profound and durable responses is highly anticipated. The lack of efficacy in MSS CRC is disappointing and strategies to convert these 'cold' tumors are needed. Further elucidation of optimal use of treatment sequences, combinations and novel agents will improve outcomes.

Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects.

Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.

A 2020 update of anal cancer: the increasing problem in women and expanding treatment landscape.

INTRODUCTION: Anal cancer is a rare malignancy with increasing incidence, notably in women. This disease is highly associated with HPV infection and its incidence and mortality are currently rising. Most patients present with localized disease which has a high survival after definitive treatment with chemoradiation. For patients who develop metastatic disease or present with this de novo, survival is poor. AREAS COVERED: This review provides a summary of current literature on anal cancer. With a focus on women, this includes current epidemiological trends, role of HPV, and the current and future treatment landscape, including HPV vaccination and immunotherapy. Screening currently focusses on HIV-positive men, missing most female cases. In curative disease, trials are investigating treatment de-intensification in good prognostic groups. Immunotherapy is showing early promise in the advanced disease setting. EXPERT OPINION: Similar to cervical cancer, anal cancer is strongly associated with HPV, and therefore, broader implementation of screening programs may reduce its incidence. HPV vaccination is expected to reduce the development of (pre)malignant anal lesions. The emergence of biomarkers will assist patient treatment selection, allowing optimal balance of treatment efficacy and morbidity. It is hoped that new treatment approaches, including immunotherapy, will improve outcomes. International collaboration is needed.