Comment on 'Pre-operative nomogram for the identification of lymph node metastasis in early cervical cancer'.

Sir,

We read with interest the article by Kim ), highlighting important challenges in pre-operative lymph node staging in early-stage cervical cancer.

From our point of view the article warrants further debate:

First question: Is there really a commitment to offer lymphadenectomy to all women with early-stage cervical cancer?

Second question: Is there an algorithm or nomogram to assess the nodal risk involvement to better select women who can really benefit from retroperitoneal surgical staging?

Third question: What is the impact of those tools in the decision-making process in women desiring to preserve fertility?

Presence of nodal metastasis is one of the most important risk factors for recurrence in surgically treated patients with early-stage cervical cancer (Sevin ). The incidence of pelvic lymph node metastasis in stage IB cervical cancer ranges from 11.5 to 21.7% (Morice ; Gien and Covens, 2009).

In the series of Kim , 81.6% of patients were diagnosed with cervical cancer with a low risk for nodal involvement. In such patients, PET/CT seems to have limited impact as it is not sensitive enough to assess lymph node status.

PET/CT has a spatial resolution limit equal to or lower than 5 mm, and considering its low sensitivity for detection of lymph node metastasis, in our opinion, it seems to have a limited impact on the management of early-stage cervical cancer patients with tumour size smaller than 4 cm.

In a previous series of selected early-stage cervical cancer patients (n=159), we found a rate of nodal metastases of 8% in women with clinical tumour size less than 2 cm, and 34% in women with tumour diameter 2–4 cm. In this low-risk population 56% of lymph node-positive patients (34 of 61) demonstrated nodal metastatic deposits <5 mm. PET/CT sensitivity and negative predictive values (NPVs) were 32.1 and 69.2%, respectively (Signorelli ).

In our recent study (Crivellaro ), we found the mean MTV (Metabolic Tumour Volume) of patients with tumours clinically larger than 2 cm to be significantly higher (17.0 ml) than that of patients with smaller tumours (6.4 ml), and the rate of nodal metastases in the first and second groups was 33 and 9%, respectively.

Sentinel node (SN) biopsy has gained attention, because emerging data from retrospective studies have highlighted its prognostic impact on survival from micrometastases (Gortzak-Uzan ). A recent study (Cibula ) confirmed preliminary data in a large cohort of 645 patients with early-stage cervical cancer undergoing surgical treatment, including SN biopsy. The presence of micrometastasis in SN was associated with significantly reduced overall survival, which corresponded to the survival in patients with macrometastasis.

This scenario underlines the importance of micrometastasis in early-stage disease, raising important considerations for the subgroup of young women candidates for conservative treatment, in whom identification of algorithms and pre-operative nomograms incorporating SN should be useful.

In our Department, women with tumours greater than 2 cm (stage 1B1–IIA1) with negative nodal involvement after pelvic lymphadenectomy and SN mapping are offered neoadjuvant chemotherapy with three cycles of TIP (Cisplatin, Ifosfamide and Paclitaxel). In cases of optimal pathologic response (CR+PR1) we perform a simple trachelectomy.

Because micrometastasis seems to be an independent prognostic factor for survival in early-stage disease, and considering that negative pre-operative workup for nodal metastasis still has a high false-negative rate, SN mapping must be incorporated in fertility-sparing surgery.

In case of bulky disease, achievement of an optimal pathologic response after neoadjuvant chemotherapy seems to be a strong independent predictor of survival even in conservative approach (Marchiole ); therefore, considering the higher risk for relapse, in case of suboptimal response (PR2 o more) we omit a conservative approach in favour of radical surgery.

The debate on whether or not to perform radical lymphadenectomy in early cervical cancer appears strange, considering the outcome in breast cancer, as the publication of the results of Z0011 showed no outcome differences between axillary dissection and no further axillary surgery in patients with positive SN, raising doubts on the role of SN biopsy. The SOUND randomised trial comparing SN biopsy with mere observation in patients with a negative axillary ultrasound who are small breast cancer candidates for breast-conserving surgery is ongoing at the European Institute of Oncology of Milan (Gentilini and Veronesi, 2012).

Prospectively, application of integrated imaging and SN algorithms could be ‘traded-off' between no nodal dissection and systematic lymphadenectomy in patients with early-stage cervical cancer, minimising morbidity and the false-negative rate of SN mapping and tailoring the treatment of patients with early-stage cervical cancer.