Elsevier

The Lancet Oncology

Volume 13, Issue 5, May 2012, Pages e212-e220
The Lancet Oncology

Review
Nodal-staging surgery for locally advanced cervical cancer in the era of PET

https://doi.org/10.1016/S1470-2045(12)70011-6Get rights and content

Summary

Chemoradiation therapy is deemed the standard treatment by many North American and European teams for treatment of locally advanced cervical cancer. The prevalence of para-aortic nodal metastasis in these tumours is 10–25%. PET (with or without CT) is the most accurate imaging modality to assess extrapelvic disease in such tumours. The true-positive rate of PET is high, suggesting that surgical staging is not necessary if uptake takes place in the para-aortic region. Nevertheless, false-negative results (in the para-aortic region) have been recorded in 12% of patients, rising to 22% in those with uptake during PET of the pelvic nodes. In such situations, laparoscopic surgical para-aortic staging still has an important role for detection of patients with occult para-aortic spread misdiagnosed on PET or PET-CT, allowing optimisation of treatment (extension of radiation therapy fields to include the para-aortic area). Complications of the laparoscopic procedure were noted in 0–7% of patients. Survival of individuals (missed by PET) with para-aortic nodal metastasis of 5 mm or less (and managed by extended field chemoradiation therapy) seems to be similar to survival of those without para-aortic spread, suggesting a positive therapeutic effect of the addition of staging surgery. Nevertheless, the effect on survival of potential delay of chemoradiation owing to use of PET and staging surgery, and acute and late complications of surgery followed by chemoradiation therapy (particularly in case of extended field chemoradiation to para-aortic area), need to be studied.

Introduction

Chemoradiation therapy combines external beam radiation therapy and cisplatin-based chemotherapy with intracavitary brachytherapy. It is judged by many North American and European teams the standard treatment for patients with a locally advanced cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IB2 or higher).1

Nodal metastasis in women with locally advanced cervical cancer, together with tumour volume and clinical stage, is the strongest prognostic factor for survival.2, 3, 4, 5 Thus, accurate pretherapeutic detection of nodal spread is key for improvement of disease control and patients' survival. Pelvic nodal involvement is noted in 30–50% of affected women but, whatever the stage of disease, pelvic nodes are included routinely in chemoradiation fields and receive a local boost when necessary.1 Para-aortic nodes are involved in 10–25% of patients; systematic extension of radiation fields to this area is associated with increased morbidity, so this strategy should be considered only if para-aortic nodal spread is either highly likely at imaging or proven by pathological examination. Therefore, accurate information about para-aortic nodal status is crucial.

Pretherapeutic staging has an important role in management of women with locally advanced cervical cancer. PET, on its own or combined with CT, raises rates of detection of extrapelvic disease compared with conventional imaging (CT or MRI).6, 7 PET might increase patients' survival by modification of treatment modalities detecting extrapelvic disease.6 Although PET is valuable for detection of extrapelvic organ metastasis, it is disappointing for recognition of small-volume metastases. Staging surgery could enable the clinician to offer individualised management. Although surgical staging is feasible, its real benefit (in terms of boosting survival) versus clinical assessment by conventional imaging continues to be discussed.8 Indeed, surgery might increase treatment morbidity and affect and delay treatment. We reviewed published studies to investigate whether para-aortic staging surgery and PET (alone or with CT) affect outcomes and survival of women with locally advanced cervical cancer.

Section snippets

Imaging of para-aortic lymph nodes

Criteria for lymph-node involvement on CT and MRI are based on size and morphology. A node is judged suspicious when shape is spherical and the smallest diameter is greater than 10 mm. MRI is the preferred method to assess local spread of a cervical tumour. However, PET seems to be more sensitive than MRI for detection of pelvic metastatic node disease.9 Findings of a meta-analysis indicate that both MRI and CT have low sensitivity (respectively, 55·5% and 57·5%) for recognition of para-aortic

Staging surgery for para-aortic nodes

30–40 years ago, para-aortic lymphadenectomy for gynaecological cancers was undertaken by laparotomy.27, 28, 29 The substantial morbidity associated with this approach led to its replacement during the 1990s by laparoscopy. Laparoscopic surgery can be undertaken by either the transperitoneal or the extraperitoneal approach.30, 31

The pattern of para-aortic dissection is important because it could affect the therapeutic strategy and morbidity of lymphadenectomy. Common iliac involvement might

Management

Many protocols for treatment of locally advanced cervical cancer have been analysed, including extended fields of radiation therapy alone (before the era of chemoradiation), nodal surgery followed by radiation therapy, nodal surgery followed by pelvic radiation therapy alone and adjuvant chemotherapy, and chemotherapy alone. As far as we know, these modalities have not been compared in a randomised trial.

Surgical techniques based on anatomical and embryologically defined compartments have been

Conclusion

PET or PET-CT is the most accurate imaging method to assess extrapelvic disease in locally advanced cervical tumours. Its high true-positive rate suggests that surgical staging is unnecessary when uptake is noted in the para-aortic area. However, the overall false-negative rate of para-aortic node involvement is around 12%, mainly attributable to non-detectable nodal disease (≤5 mm). If we only consider patients with definite nodal uptake in the pelvis, the rate of false-negative para-aortic

Search strategy and selection criteria

We identified data for this Review from searches of Medline, Current Contents, PubMed, and from references in relevant articles, from 1985 to June, 2011, with the following search terms: “locally advanced cervical cancer”, “staging surgery”, “laparoscopic paraaortic lymphadenectomy”, “paraaortic lymphadenectomy”, “PET”, “PET-CT”. Articles published in English (or with at least an abstract in English) were included. In case of repeat publications by the same team on a similar topic, the series

References (83)

  • JL Belinson et al.

    Paraaortic lymphadenectomy in gynecologic cancer

    Gynecol Oncol

    (1979)
  • A Rafii et al.

    A comparative study of laparoscopic extraperitoneal laparoscopy with the use of ultrasonically activated shears

    Am J Obstet Gynecol

    (2009)
  • PL Benedetti-Panici et al.

    Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy

    Gynecol Oncol

    (1996)
  • M Possover et al.

    Left-sided suprarenal retrocrural paraaortic lymphadenectomy in advanced cervical cancer by laparoscopy

    Gynecol Oncol

    (1998)
  • HJ Buchsbaum

    Extrapelvic lymph node metastases in cervical carcinoma

    Am J Obstet Gynecol

    (1979)
  • LaPolla et al.

    The influence of surgical staging on the evaluation and treatment of patients with cervical carcinoma

    Gynecol Oncol

    (1986)
  • EB Weiser et al.

    Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study)

    Gynecol Oncol

    (1989)
  • A Hasenburg et al.

    Evaluation of patients after extraperitoneal lymph node dissection and subsequent radiotherapy for cervical cancer

    Gynecol Oncol

    (2002)
  • D Denschlag et al.

    Evaluation of patients after extraperitoneal lymph node dissection for cervical cancer

    Gynecol Oncol

    (2005)
  • KN Moore et al.

    Extraperitoneal paraaortic lymph node evaluation for cervical cancer via pfannenstiel incision: technique and peri-operative outcomes

    Gynecol Oncol

    (2008)
  • FO Recio et al.

    Pretreatment transperitoneal laparoscopic staging pelvic and paraaortic lymphadenectomy in large (≥5 cm) stage IB2 cervical carcinoma: report of a pilot study

    Gynecol Oncol

    (1996)
  • J Vidaurreta et al.

    Laparoscopic staging in locally advanced cervical carcinoma: a new possible philosophy?

    Gynecol Oncol

    (1999)
  • D Dargent et al.

    Technical development and results of left extraperitoneal laparoscopic paraaortic lymphadenectomy for cervical cancer

    Gynecol Oncol

    (2000)
  • H Hertel et al.

    Laparoscopic staging compared with imaging techniques in the staging of advanced cervical cancer

    Gynecol Oncol

    (2002)
  • T Tillmanns et al.

    Safety, feasibility, and costs of outpatient laparoscopic extraperitoneal aortic nodal dissection for locally advanced cervical carcinoma

    Gynecol Oncol

    (2007)
  • A Fichez et al.

    Left extraperitoneal laparoscopic paraaortic lymphadenectomy: morbidity and learning curve of the technique

    Gynecol Obstet Fertil

    (2007)
  • B Occelli et al.

    De novo adhesions with extraperitoneal endosurgical para-aortic lymphadenectomy versus transperitoneal laparoscopic para-aortic lymphadenectomy: a randomized experimental study

    Am J Obstet Gynecol

    (2000)
  • MC Yenen et al.

    Port-site metastasis after laparoscopic extraperitoneal paraaortic lymphadenectomy for stage IIb squamous cell carcinoma of the cervix

    J Minim Invasive Gynecol

    (2009)
  • BA Fine et al.

    Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery

    Int J Radiat Oncol Biol Phys

    (1995)
  • W Mackillop et al.

    Waiting for radiotherapy in Ontario

    Int J Radiat Oncol Biol Phys

    (1994)
  • S Marnitz et al.

    Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer?

    Gynecol Oncol

    (2005)
  • M Höckel et al.

    Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis

    Lancet Oncol

    (2009)
  • MS Piver et al.

    Five-year survival (with no evidence of disease) in patients with biopsy-confirmed aortic node metastasis from cervical carcinoma

    Am J Obstet Gynecol

    (1981)
  • JH Malfetano et al.

    Aggressive multimodality treatment for cervical cancer with paraaortic lymph node metastases

    Gynecol Oncol

    (1991)
  • N Husseinzadeh et al.

    Chemotherapy and extended-field radiation therapy to para-aortic area in patients with histologically proven metastatic cervical cancer to para-aortic nodes: a phase II pilot study

    Gynecol Oncol

    (1994)
  • PW Grigsby et al.

    Twice-daily fractionation of external irradiation with brachytherapy and chemotherapy in carcinoma of the cervix with positive para-aortic lymph nodes: phase II study of the Radiation Therapy Oncology Group 92-10

    Int J Radiat Oncol Biol Phys

    (1998)
  • PW Grigsby et al.

    Long-term follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes

    Int J Radiat Oncol Biol Phys

    (2001)
  • MA Varia et al.

    Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy—a Gynecologic Oncology Group study

    Int J Radiat Oncol Biol Phys

    (1998)
  • W Small et al.

    Extended-field irradiation and intracavitary brachytherapy combined with cisplatin chemotherapy for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of ARM 1 of RTOG 0116

    Int J Radiat Oncol Biol Phys

    (2007)
  • YS Kim et al.

    High-dose extended-field irradiation and high-dose-rate brachytherapy with concurrent chemotherapy for cervical cancer with positive para-aortic lymph nodes

    Int J Radiat Oncol Biol Phys

    (2009)
  • JL Walker et al.

    A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: a Gynecologic Oncology Group study

    Gynecol Oncol

    (2009)
  • Cited by (170)

    • Interest of para-aortic lymphadenectomy for locally advanced cervical cancer in the era of PET scanning

      2022, European Journal of Obstetrics and Gynecology and Reproductive Biology
    View all citing articles on Scopus
    View full text