What Para-Aortic Nodal Involvement Predicts About Survival in PET-CT–Negative Locally Advanced Cervical Cancer 

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In a study reported in the Journal of Clinical Oncology, Sebastien Gouy, MD, of Institut Gustave Roussy and colleagues evaluated survival outcomes in patients with locally advanced cervical cancer and negative positron-emission tomography/computed tomography (PET-CT) imaging results who underwent laparoscopic para-aortic staging surgery before chemoradiotherapy.1 They found that event-free survival was similar in patients with no nodal involvement and in those with nodal metastasis ≤ 5 mm but significantly poorer in those with nodal involvement > 5 mm. Results for overall survival were similar.

Study Details

The prospective study was performed in three French comprehensive cancer centers. Overall, it included 237 patients treated from 2004 to 2011 for locally advanced cervical cancer who had PET-CT-negative imaging of the para-aortic area and underwent laparoscopic para-aortic lymphadenectomy. Radiation fields were extended to the para-aortic area when para-aortic nodes were found to be involved. Chemoradiotherapy modalities were homogeneous across the three institutions. Patients with a poor-prognosis histologic subtype or peritoneal carcinosis were excluded from the study.

Clinical International Federation of Gynecology and Obstetrics stages were IB2 in 79 patients (33%), IIA in 10 (5%), IIB in 121 (50%), III in 22 (10%), and IVA in 5 (2%). Histologic subtype was squamous carcinoma in 129 (84%), and the remainder had adenocarcinoma/adenosquamous lesions. The vast majority of patients had conformational radiation therapy (95%), cisplatin-based concurrent chemotherapy (99.6%), and uterovaginal brachytherapy (97%).

In total, 29 patients (12.2%) had nodal involvement—ie, false-negative PET-CT results—including 16 (6.8%) with a para-aortic nodal metastasis measuring > 5 mm and 13 (5.5%) with a nodal metastasis measuring ≤ 5 mm. Among patients with para-aortic metastasis ≤ 5 mm, 10 had a single metastatic node and 3 had two positive nodes. Among patients with metastasis > 5 mm, 3 had a single metastatic node.

Survival Outcomes

In the entire population, overall survival was 88% at 3 years, 86% at 4 years, and 78% at 5 years, and event-free survival was 71%, 66%, and 62%, respectively. Event-free survival rates at 3 years in patients without para-aortic nodal involvement, with metastasis measuring ≤ 5 mm, and with metastasis measuring > 5 mm were 74%, 69%, and 17%, respectively (P < .001). Respective 3-year overall survival rates were 89%, 100%, and 40% (P = .04).

Analysis by number of involved nodes showed 3-year event-free survival rates of 74%, 81%, and 16% for those with 0 involved nodes, 1 involved node, and ≥ 2 involved nodes, respectively (P < .001).

Prognostic Factors

Overall, factors that were prognostic for event-free survival were involved para-aortic nodes vs nodes free of disease (HR = 2.6, P = .003), pN1 > 5 mm vs pN0 (HR = 5.8, P < .001), pN1 > 5 mm vs pN0/pN1 ≤ 5 mm (HR = 5.8, P < .001), pN1 ≥ 2 nodes vs pN0 (HR = 4.4, P < .001). There was a borderline significant effect for delay between PET-CT and chemotherapy ≥ 45 days vs < 45 days (HR = 1.9, P = .06).

Factors that were not prognostic for event-free survival were histologic subtype, stage, pelvic uptake on PET, duration of chemotherapy, delay between surgery and chemotherapy, and delay between PET-CT and chemotherapy ≥ 30 vs < 30 days.

The investigators concluded: “To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with para-aortic nodal metastasis ≤ 5 mm and patients without para-aortic lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with para-aortic nodal involvement > 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.” ■

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1. Gouy S, Morice P, Narducci F, et al: Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging. J Clin Oncol. July 15, 2013 (early release online).

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