Residual Cancer Stem Cells after Interval Cytoreductive Surgery following Neoadjuvant Chemotherapy Could Result in Poor Treatment Outcomes for Ovarian Cancer

Abstract

The objective of this review is to discuss the common surgical strategy of cytoreductive surgery after neoadjuvant chemotherapy, with an emphasis on incorporating extensive cytoreductive surgery to remove traces of regressed tumor. A review of the literature regarding cytoreductive surgery after neoadjuvant chemotherapy and cancer stem cells is given together with the authors’ own experience and comments. Most ovarian cancer cells consist of transformed cells that regress after neoadjuvant chemotherapy. Therefore, the extent of cytoreductive surgery usually tends to be limited because only visible tumors are removed. Scar tissue, which represents tumor after neoadjuvant chemotherapy, may contain cancer stem cells. This leads to chemotherapy-resistant cancer stem cells to persist in patients who have received neoadjuvant chemotherapy. If the extent of cytoreductive surgery is preserved based on initial images, and includes all scar tissue suggestive of previously existing ovarian cancer in patients who underwent interval debulking surgery after neoadjuvant chemotherapy, treatment outcome will be improved or be comparable to patients who underwent primary cytoreductive surgery with minimal morbidity. Further basic and clinical investigation is needed to serve as a standard surgical paradigm in the management of advanced ovarian cancer. Currently, the gynecologic oncologist should remove all traces of regressed tumor after neoadjuvant chemotherapy to eradicate potential cancer stem cells. Further investigation to clarify the role of cancer stem cell in the surgical management of ovarian cancer is warranted.

Primary debulking surgery vs. neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

“…Chemoresistance of ovarian cancer may be induced by NAC [13], leading to a bad prognosis if recurrence occurs. Although the diameter of metastatic tumor could be reduced by NAC, even to less than 1 cm, the tumor tissue may contain cancer stem cells, which is responsible for chemotherapy-resistant recurrence [14]. Meanwhile, because of the chemotherapy prior to surgery, the planned cycles of postsurgical chemotherapy may be less in NAC group than PDS group.…”

Impact of Laparoscopy to Assess Resectability in Stage IIIC Epithelial Ovarian, Tubal and Peritoneal Cancer Patients

“…As a result, he was able to conclude that primary cytoreductive surgery offers an increased survival for patients compared to NACT in the absence of RT and when RT < 1 cm. It is worth noting that for the patients in the neoadjuvant therapy group, the fact that they were diagnosed as non-resectable gives them a worse prognosis, probably because of the tumor's intrinsic biology and tumor stem cells' resistance to chemotherapy [7,37], regardless of the surgery that may be performed. As a consequence, the results of all nonrandomized studies show a certain bias, given that patients with multiple comorbidities or patients with the worse ECOG Score, or the highest tumor burden are usually assigned to the interval surgery group.…”

Neoadjuvant chemotherapy in advanced ovarian cancer: latest results and place in therapy

“…A population of chemotherapy-resistant stem cells selected during NACT and not debulked in IDS may play a role in EOC recurrence. It was suggested that all tissue showing traces of tumor, that is, scar tissue, should be removed during IDS [Lim et al 2010]. More recently, another author reported that TP53-K351N mutation was involved in platinum resistance after NACT [Zhang et al 2014].…”