Chances, risks and limitations of neoadjuvant therapy in surgical oncology

Abstract

Over the last decades, neoadjuvant treatment has been established as a standard of care for a variety of tumor types in visceral oncology. Neoadjuvant treatment is recommended in locally advanced esophageal and gastric cancer as well as in rectal cancer. In borderline resectable pancreatic cancer, neoadjuvant therapy is an emerging treatment concept, whereas in resectable colorectal liver metastases, neoadjuvant treatment is often used, although the evidence for improvement of survival outcomes is rather weak. What makes neoadjuvant treatment attractive from a surgical oncology viewpoint is its ability to shrink tumors to a smaller size and to increase the chances for complete resection with clear surgical margins, which is a prerequisite for cure. Studies suggest that local tumor control is increased in some visceral tumor types, especially with neoadjuvant chemoradiotherapy. In some other studies, a better control of systemic disease has contributed to significantly improved survival rates. Additionally, delaying surgery offers the chance to bring the patient into a better general condition for major surgery, but it also confers the risk of progression. Although it is a relatively rare event, cancers may progress locally during neoadjuvant treatment or distant metastases may occur, jeopardizing a curative surgical treatment approach. Although this is seen as risk of neoadjuvant treatment, it can also be seen as a chance to select only those patients for surgery who have a better control of systemic disease. Some studies showed increased perioperative morbidity in patients who underwent neoadjuvant treatment, which is another potential disadvantage. Optimal multidisciplinary teamwork is key to controlling that risk. Meanwhile, the neoadjuvant treatment period is also used as a “window of opportunity” for studying the activity of novel drugs and for investigating predictive and prognostic biomarkers of chemoradiotherapy and radiochemotherapy. Although the benefits of neoadjuvant treatment have been clearly established, the risk of overtreatment of cancers with an unfavorable prognosis remains an issue. All indications for neoadjuvant treatment are based on clinical staging. Even if staging is done meticulously, making use of all recommended diagnostic modalities, the risk of overstaging and understaging remains considerable and may lead to false indications for neoadjuvant treatment. Finally, despite all developments and emerging concepts in medical oncology, many cancers remain resistant to the currently available drugs and radiation. This may in part be due to specific molecular resistance mechanisms that are marginally understood thus far. Neoadjuvant treatment has been one of the major advances in multidisciplinary oncology in the last decades, requiring a dedicated treatment team and an optimal infrastructure for complex oncology care. This article discusses the goals and novel directions as well as limitations in neoadjuvant treatment of visceral cancers.

Disparities in neoadjuvant chemotherapy for pancreatic adenocarcinoma with vascular involvement

“…Since its introduction in the 1950s, NAT has been used in a variety of cancers to improve surgical resectability and reduce systemic disease burden to prolong survival [ 15 ]. For patients with PDAC, it may provide a chance to complete a full treatment of multiagent chemotherapy, as many patients are too frail postoperatively to undergo scheduled adjuvant therapy [ 9 ].…”

Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer

“…NAT relies on clinical staging. Insufficient staging can lead to undertreatment, and over staging can lead to the overuse of NAT (53). In addition, there is another risk of overtreatment of cancers with a poor prognosis (54), see Table 4.…”

The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer

“…Similarly, the CROSS trial demonstrated that neoadjuvant chemoradiotherapy improved median overall survival from 24 to 49.4 months vs. surgery alone [ 29 ]. However, only 25% to 30% of patients achieve a partial or complete pathological response [ 30 , 31 ], and it carries a 0.5 to 2% mortality rate [ 32 ]. Early identification of patients that respond well could improve outcomes by preventing the administration of treatment regimens that are unlikely to be effective and facilitating treatment modulation [ 33 ].…”

“…By administering NAT in patients who do not respond well, surgery is delayed, which if carried out earlier may have proven more effective. The main benefits of NAT are the increased chance of complete resectability of the primary tumour, as reduced tumour mass induced by NAT decreases the area of resection required, as well as improved prognostic outcome due to the decreased incidence of nodal micrometasteses [ 32 , 35 , 36 ]. On the contrary, tumour progression during therapy can occur in those patients who do not respond well to NAT or conversely overtreatment of tumours with a favourable prognosis that are unlikely to respond to NAT.…”