Value of Neoadjuvant Chemotherapy for Newly Diagnosed Advanced Ovarian Cancer: A European Perspective

Abstract

The timing of debulking surgery in advanced ovarian cancer (AOC) has been the focus of debate and controversy in the international community for almost a decade. [1][2][3][4] Although supporters of primary debulking surgery (PDS) advocate significantly better overall survival (OS) and progression-free survival rates, with even a significantly favorable impact on the patterns of relapse, 4 opponents argue higher morbidity in a highly heterogeneous and often fatal disease.1-3 For more than two decades, we have known that each 10% increase in maximal cytoreduction is associated with a 5.5% increase in median survival, even after controlling for all other known patient-and tumor-specific variables. 5,6 However, because of the unusual tumor biology and clinical behavior of AOC, with a typical diffuse peritoneal dissemination, in the majority of cases complete debulking is associated with multivisceral resections that require extensive surgical expertise, training, and infrastructural support to not lead to an exponential increase in morbidity. 7Neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) have been considered as ways to reduce surgical morbidity; however, the oncologic safety of these approaches has never been proven in a maximal effort setting of high surgical expertise.2,3 The inconsistent quality of the surgical trials that have addressed this matter so far; the broad variation in practice nationally and internationally; and the still unanswered questions of fragility scores, biomarkers, and valid predictors of operability have led to strong polarization and controversy worldwide, which gives a clear signal of the need for further evidence.As a network of European institutions dedicated to highquality gynecologic oncology care, we address some key points about this highly controversial topic and express some serious concerns related to a potential patient's compromise through suboptimal therapeutic strategies. Our statement is timed to the recent publication of the Society of Gynecologic Oncology and ASCO statement about the use of NAC in AOC, which provides guidance on the optimal timing of surgery and identifies diagnostic tools that facilitate the patient selection process.

Upfront debulking surgery versus interval debulking surgery for advanced tubo‐ovarian high‐grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC

“…Unfortunately, both studies suffered from several sources of bias including participating centers with low recruitment rates per year, low rates of complete resection, and lower than expected survival rates after UDS. These limitations hindered the extrapolation of the findings to general clinical application . Hence, the European and United States guidelines, including the National Cancer Network guidelines, still recommend as the preferred treatment for these patients' UDS followed by systemic chemotherapy, provided that it has at least a high likelihood of achieving residual disease less than 1 cm with acceptable morbidity .…”

Operative Therapie des Ovarialkarzinoms

“…Alleine aus dieser Tatsache wurde zum Teil unreflektiert und verfrüht der Schluss gezogen, Patientinnen mit einem fortgeschrittenen Ovarialkarzinom durchaus neoadjuvant behandeln zu können. In der Argumentation wurde jedoch nicht berücksichtigt, dass der Anteil makroskopisch tumorfrei oder zumindest optimal operierter Patientinnen deutlich unter dem internationalen Vergleich lag [25]. Während man heute im fortgeschrittenen Stadium von einer erreichbaren makroskopischen Tumorfreiheit von über 60 % ausgeht, wurden in den genannten Studien jeweils nur knapp 20 % im Primäransatz tumorfrei operiert [23,24].…”

“…120 Minuten, sodass die Effektivität einer Debulkingoperation durchaus infrage gestellt werden darf. Die rezidivfreie Zeit und die Überlebenszeit waren deutlich geringer als in vergleichbaren Studien [25]. Unabhängig von dieser Diskussion zur Frage des therapeutischen Ansatzes gibt es Patientinnen, bei denen eine primäre Operation nicht sinnvoll ist.…”

Evolving Concepts in the Management of Newly Diagnosed Epithelial Ovarian Cancer

“…As such, the impact of aggressive primary surgery in women with high disease burden remains to be established, pending results from TRUST (Trial on Radical Upfront Surgery in Advanced Ovarian Cancer). 16 Triage of patients for PCS or NACT with consideration of interval cytoreductive surgery can be challenging because of imaging studies, which may under-or overestimate the extent of invasive or metastatic disease. Validated models can predict the likelihood of achieving complete primary cytoreduction on the basis of clinical factors.…”