Ovarian cancer is the sixth most common cancer among women in Europe with over 80% of cases diagnosed at an advanced stage of disease. International guidelines indicate primary debulking surgery as first approach in patient with advanced ovarian cancer in order to obtain an optimal cytoreduction with radical intent; in cases of tumor not primarily operable or patient not fit for radical surgery, neoadjuvant therapy (NACT) followed by interval debulking surgery (IDS) is a widely employed option [Citation1]. The goal of surgical treatment is to obtain no gross tumor residual (NGTR), which is strongly associated to improved overall survival [Citation2].
The concept of NGTR has been closely related to the disease confined into abdominal cavity; however, the correct management and prognostic significance in case of metastatic disease outside the abdomen remain still not very clear. Currently, in order to achieve NGTR, current surgical algorithms recommend systematic lymphadenectomy extended to both pelvic and para-aortic lymph nodes and eventual retroperitoneal bulky lymph nodes; however, systematic lymphadenectomy is not commonly extended to lymph nodes above the diaphragm.
Recently, there has been an increasing awareness for prognostic significance of metastatic ovarian disease extended to cardiophrenic lymph nodes stations (CPLNs) and its possible association with a worse overall survival [Citation3]. In particular, the term CPLNs is referred to supradiaphragmatic or pericardial lymph nodes, considered one of the main thoracic nodal stations for the lymphatic drainage from the abdominal cavity. Several techniques to perform CPLN lymphadenectomy are currently adopted, including transdiaphragmatic, video-assisted thoracoscopic (VATS) or subxiphoid approaches.
Nevertheless, the clinical and prognostic roles of CPLNs in advanced ovarian cancer has been investigated only during primary debulking surgery; otherwise, the feasibility of this approach on patients who received NACT followed by IDS remains to be elucidated.
It should be noted that, given the innovative nature of these studies, the criteria employed to identify suspicious CPLN are not standardized. The malignant involvement of CPLN has been supposed on the pre-operative computer tomography (CT) scan by using qualitative or quantitative parameters; these include a qualitative examination based on size, heterogeneity, and architecture (i.e. irregular border, round in shape, heterogeneous internal attenuation) or a quantitative assessment based on the length of the short axis of the node (ranging from 5 to 10 mm).
Despite of this unclear context, in these studies, the presence of enlarged CPLNs has been reported to be a variable percentage of 15-28% on pre-operative CT scan of the thorax of patients with advanced ovarian cancer, especially for those with disease extended to the upper abdomen [Citation4, Citation5]. The subsequent post-operative histological examination of these suspicious lymph nodes has revealed the presence of metastatic disease in a variable percentage, ranging from 45% to 95% [Citation6, Citation7].
Interestingly, in Journal of Investigative Surgery the first case series aiming to explore the feasibility of CPLNs assessment also in patient who receive NACT followed by IDS for advanced ovarian cancer has been recently published [Citation8]. Notably, in this retrospective study authors defined suspicious CPLNs by recurring to both clinical (objective palpation) and radiological criteria (> 7 mm on the short axis for the lymph node size on the CT-scan after NACT). A total of 21 ovarian cancer stage IV patients treated with NACT followed by IDS were enrolled; 66.6% of patients had enlarged lymph nodes on CT-scan after NACT; the final histological examination of the CPLNs reported metastatic disease in 57% of the cases [Citation8].
In conclusion, the available literature preliminary demonstrates the safety and feasibility of the cardiophrenic lymphadenectomy for treating advanced ovarian cancer when it consents to achieve an optimal radicality; in particular, this complex surgical procedure should be done by experienced surgical gynecologist after an accurate preoperative diagnostic management [Citation7]. At the same time, in order to avoid overtreatment and to reduce morbidity, more attention should be given to use of non-invasive imaging, such as positron emission tomography-CT (PET-CT) or ultrasound, in order to achieve a greater precision in identifying the lymph nodes suspected for metastatic disease.
The prognostic significance of this approach remains still uncertain, although CPLNs metastases seem to be associated with impaired progression free survival and overall survival in patients with macroscopically completely resected tumor [Citation9]. At this proposal, further researches on this topic are needed in order to better evaluate the role of CPLN lymphadenectomy and its long-term survival benefit both in case of primary debulking surgery or NACT followed by IDS.
Disclosure statement
The authors have no conflict of interest.
References
- Armstrong DK, Alvarez RD, Bakkum-Gamez JN, et al. NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019. J Natl Compr Canc Netw. 2019;117(8):896–909. doi:10.6004/jnccn.2019.0039.
- Wallace S, Kumar A, Mc Gree M, et al. Efforts at maximal cytoreduction improve survival in ovarian cancer patients, even when complete gross resection is not feasible. Gynecol Oncol. 2017;145(1):21–26. doi:10.1016/j.ygyno.2017.01.029.
- Raban O, Peled Y, Krissi H, et al. The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer. Gynecol Oncol. 2015;138(2):259–262. doi:10.1016/j.ygyno.2015.05.007.
- Prader S, Harter P, Grimm C, et al. Surgical management of cardiophrenic lymph nodes in patients with advanced ovarian cancer. Gynecol Oncol. 2016;141(2):271–275. doi:10.1016/j.ygyno.2016.03.012.
- Holloway BJ, Gore ME, A'Hern RP, et al. The significance of paracardiac lymph node enlargement in ovarian cancer. Clin Radiol. 1997;52(9):692–697. doi:10.1016/S0009-9260(97)80034-7.
- Yoo HJ, Lim MC, Song YJ, et al. Transabdominal cardiophrenic lymph node dissection (CPLND) via incised diaphragm replace conventional video-assisted thoracic surgery for cytoreductive surgery in advanced ovarian cancer. Gynecol Oncol. 2013;129(2):341–345. doi:10.1016/j.ygyno.2012.12.023.
- Garbi A, Zanagnolo V, Colombo N, et al. Feasibility of transabdominal cardiophrenic lymphnode dissection in advanced ovarian cancer: initial experience at a tertiary center. Int J Gynecol Cancer. 2017;27(6):1268–1273. doi:10.1097/IGC.0000000000000983.
- The feasibility of cardiophrenic lymphnode assessment and removal in patients requiring diaphragmatic resection during interval debulking surgery for ovarian cancer. J Invest Surg. 2021;34(7):756–762. doi:10.1080/08941939.2019.1690077.
- Prader S, Vollmar N, Du Bois A, et al. Pattern and impact of metastatic cardiophrenic lymph nodes in advanced epithelial ovarian cancer. Gynecol Oncol. 2019;152(1):76–81. doi:10.1016/j.ygyno.2018.11.001.