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Cancer immunotherapy; Surgery; Neoadjuvant; Checkpoint inhibitors; Tumor recurrence; Immune-related adverse events

Cancer surgery has long been the cornerstone of treatment for solid tumors, often offering the best chance for a cure, especially in the early stages. However, many cancers present with a high risk of recurrence due to residual microscopic disease or metastases. The advent of cancer immunotherapy—targeting immune checkpoints, activating T-cells, and harnessing monoclonal antibodies—has transformed oncology by offering therapies that work synergistically with the immune system to attack tumor cells. Immunotherapies such as checkpoint inhibitors (e.g., PD-1/PD-L1 and CTLA-4 inhibitors), CAR T-cell therapies, and monoclonal antibodies have demonstrated durable responses in cancers that were previously unresponsive to conventional treatments. As immunotherapies continue to demonstrate efficacy, their integration into surgical oncology is reshaping the role of surgery in cancer management. Surgeons now collaborate with oncologists to administer immunotherapy before, during, and after surgery to optimize outcomes, reduce recurrence rates, and enhance overall survival. This article discusses how cancer immunotherapy is driving innovations in surgery and how these innovations are transforming cancer care [1][2].

Immunotherapy as a Neoadjuvant Strategy

Neoadjuvant therapy refers to the administration of treatment before surgery to reduce tumor size, improve resectability, and minimize the risk of recurrence. Traditional neoadjuvant therapies primarily include chemotherapy and radiation, which aim to shrink tumors and eliminate micrometastatic disease. Immunotherapy, however, has emerged as a potent alternative or adjunct to these therapies, offering new opportunities for tumor control prior to surgical resection. In melanoma, non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC), neoadjuvant immunotherapy has shown promising results. For instance, checkpoint inhibitors such as nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) have been used before surgery to induce significant tumor regression, enabling more successful and less invasive resections. Immunotherapy has the potential to reduce the size of tumors, convert previously inoperable tumors to resectable ones, and enhance the ability to achieve negative surgical margins. In cases of early-stage melanoma, the combination of checkpoint inhibitors with surgery has led to improved disease-free survival rates, especially in high-risk patients with locally advanced disease [3][4]. One of the key advantages of neoadjuvant immunotherapy is its ability to assess tumor response in real time, which provides valuable prognostic information. Patients who exhibit a complete pathological response (pCR) to immunotherapy often show better long-term survival, prompting oncologists and surgeons to consider immunotherapy as a routine part of the preoperative regimen for certain cancers. Neoadjuvant immunotherapy, however, is not without challenges. Toxicity profiles can vary, and immune-related adverse events (irAEs) must be carefully managed, as they can impact both the patient’s health and their ability to proceed with surgery [5].

Immunotherapy During Surgery Intraoperative Implications

While the primary role of immunotherapy is typically before or after surgery, its potential for direct intraoperative application is an emerging area of interest. One of the most exciting developments is the idea of using immunotherapy during surgery to enhance the immune response to residual tumor cells and micro-metastases. Surgeons are investigating the use of intraoperative checkpoint inhibitors or other immune modulators during surgery to augment the immune system’s ability to recognize and eliminate any remaining tumor cells that might otherwise lead to recurrence. Intraoperative use of immunotherapy could help target micrometastatic disease that is invisible to the surgeon. By enhancing immune activity during the surgical procedure, it is possible to improve the immune system’s ability to detect and destroy residual cancer cells, reducing the risk of recurrence. For example, the combination of surgical resection with intraoperative administration of immune checkpoint inhibitors is being tested in clinical trials to determine its efficacy in reducing post-surgical relapse, particularly in cancers like NSCLC, colorectal cancer, and melanoma [6]. Furthermore, the integration of immunotherapy during surgery may have the potential to reduce the necessity for extensive post-surgical adjuvant therapies. If the immune system can be primed intraoperatively to eliminate residual cancer cells, the need for additional chemotherapy or radiation may be reduced, decreasing the overall treatment burden for patients.

Postoperative Immunotherapy and Minimizing Recurrence

Postoperative immunotherapy is one of the most established applications of immunotherapy in cancer surgery. After the tumor has been resected, patients often receive adjuvant immunotherapy to eliminate any remaining micrometastases or prevent tumor recurrence. This approach has been particularly successful in cancers like melanoma, NSCLC, and renal cell carcinoma, where immune checkpoint inhibitors such as nivolumab, pembrolizumab, or atezolizumab are administered to prevent relapse. In the case of melanoma, adjuvant immunotherapy has shown significant survival benefits. Studies have demonstrated that patients who receive immunotherapy after surgery experience a lower risk of recurrence compared to those who undergo surgery alone. This has led to a paradigm shift in the management of high-risk melanoma, where immunotherapy is now part of the standard postoperative regimen. Similar trends are seen in NSCLC, where adjuvant immunotherapy is becoming an increasingly common practice for patients with stage III or IV disease after resection. The integration of immunotherapy into postoperative care aims to target any residual disease that may not have been removed during surgery. This can significantly reduce the likelihood of recurrence, especially in cancers that tend to relapse after surgical resection, such as NSCLC and head and neck cancers. By enhancing the immune system’s ability to recognize and destroy residual cancer cells, immunotherapy offers a more targeted approach to reducing recurrence rates and improving overall survival [7][8].

Challenges and Future Directions

Despite the growing evidence supporting the use of immunotherapy in combination with surgery, several challenges remain. One major obstacle is the risk of immune-related adverse events (irAEs), which can include inflammation in vital organs, such as the lungs, liver, and intestines. These side effects can complicate both surgery and recovery. It is critical for clinicians to monitor patients carefully for irAEs and manage them promptly to prevent long-term complications. Another challenge is patient selection. Not all patients respond to immunotherapy, and identifying those who will benefit most from this combined approach remains an area of active research. Tumor biomarker profiling and predictive models are essential to determine which patients will have the most favorable outcomes from immunotherapy and surgery. Furthermore, research is ongoing to develop better combination strategies, including the use of immunotherapy in combination with other novel treatments such as targeted therapies, personalized vaccines, and oncolytic biotherapy [9, 10]. Future research will likely focus on refining patient selection criteria, minimizing side effects, and improving the efficacy of immune checkpoint inhibitors. The goal is to make immunotherapy more accessible and effective for a broader range of cancers and patients. Intraoperative immunotherapy, as well as the development of personalized immunotherapy regimens, may hold promise for further improving the synergy between surgery and immunotherapy in cancer management.

Conclusion

Cancer immunotherapy has significantly impacted the management of various malignancies, and its integration into surgical oncology is leading to innovative approaches for treating cancer patients. Neoadjuvant, intraoperative, and adjuvant strategies that incorporate immunotherapy are reshaping how surgeons approach cancer treatment, with the potential to reduce recurrence rates, improve survival, and enhance surgical outcomes. While there are still challenges, such as managing immune-related side effects and identifying the most suitable candidates for immunotherapy, the future of cancer surgery is increasingly intertwined with immune-based therapies. The synergy between immunotherapy and surgery offers exciting prospects for optimizing cancer treatment and improving patient outcomes.

1. Andersen BL, Anderson B, de Prosse C (1989) J Consult Clin Psycho l57: 692-771.

, ,

2. Heald RJ, Husband EM, Ryall RD (1982).Br J Surg 69: 613-616.

, ,

3. Jennings-Sanders A, Anderson ET (2003) Nur Outlook 51: 108-114.

, ,

4. Osborne MP (2007). Lancet Oncol 8: 256-265.

, ,

5. Keating N, Guadagnoli E, Landrum M (2002) J Clin Oncol 20: 1473-1479.

, ,

6. Fisher B (1977). World J Surg 1: 327-330.

, ,

7. Gilbar O, Ben-Zur H (2002) Am J Orthopsychiatry 72: 422-432.

, ,

8. Turnbull RB, Kyle K, Watson FR, Spratt J (1967) Ann Surg 166: 420-427.

, ,

9. Kornblith AB, Zhang C, Herndon JE (2003) Cancer 98: 679-689.

, ,

10. S酶ndenaa K, Quirke P, Hohenberger W, Sugihara K, Kobayashi H, et al. (2014). Int J Colorectal Dis 29: 419-428.

, ,