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New cervical cancer op trialled

Tuesday 2 June 2009

Small changes to how cervical cancer surgery is performed could improve survival by up to one-fifth, BBC News has reported. According to the website, the most common technique currently used for treating early-stage cervical cancer is radical hysterectomy, where the whole womb and nearby tissue is removed. The new technique, called total mesometrial resection (TMMR), removes a “more defined” section of tissue, based on the areas where the tumour is likely to spread.

The study behind this news report evaluated the outcomes of using TMMR to treat 212 women with cervical cancer that had not spread to the vagina or pelvic wall. After an average of about 3½ years’ follow-up, 10 women experienced cancer recurrence either in the pelvis or at distant sites and went on to receive further treatment. The rate of survival after five years was calculated to be high, at around 96%.

In contrast to conventional treatment using radical hysterectomy and radiotherapy, TMMR does not involve removal of surrounding pelvic tissues. Therefore, it has the potential advantage of reduced risk of damage to the nerve supply of the bladder, bowel and vagina, in addition to avoiding the side effects of radiotherapy. For women with early-stage cervical cancer, this is an important development. However, randomised controlled trials will now be needed to directly compare the outcomes of this technique with conventional methods.

Where did the story come from?

Professor Michael Höckel and colleagues from the University of Leipzig in Germany carried out this research. The study was funded by the University of Leipzig and published in the peer-reviewed medical journal the Lancet Oncology.

What was the new technique tested?

The authors of this study say that around two-fifths of women diagnosed with early-stage cervical cancer are candidates for a radical hysterectomy, where surgeons remove the whole uterus, cervix, a small portion of the upper part of the vagina and some soft tissue from within the pelvis. In women with high risk factors this is usually combined with radiotherapy after the surgery. The authors say that one of the principles of this surgery is the assumption that the tumour will spread in a random linear manner (straight line) across and out from the cervix.

The authors of this study made small alterations to the standard radical hysterectomy surgical technique for the treatment of early-stage cervical cancer to create a new surgical technique called total mesometrial resection (TMMR). This technique is based on the removal of only those genital tissues that have developed from a common structure in the embryo (called the Müllerian compartment). This includes the Fallopian tubes, uterus and the top and middle of the vagina, which are enclosed in complex layers of blood vessels, lymphatic tissue and connective and fatty tissue called the mesometrium.

The researchers developed the new technique to remove these structures as they had noticed that cervical cancer normally takes a relatively long period to spread outside of these tissues. TMMR removes the whole Müllerian compartment except for the bottom part of the vagina, which allows the woman to retain a vaginal cavity. The TMMR technique is used to treat women where the cancer is confined to the cervix (stage I) or may have spread to the tissues around the cervix (stage II), but not into the pelvis or other areas of the body. Within these stages, tumours can also be divided into further sub-stages, indicated with a number and letter (e.g. stage IB2) that give more information about the size and positioning of the tumour.

The technique also leaves tissues that are not part of the Müllerian compartment or the lymph node system (where the tumour may spread), such as bladder or nervous system tissue, even if they are close to the malignant tumour.

How was the new TMMR technique tested?

To test whether this technique effectively removed the tumour and stopped the cancer from spreading, the researchers set up a prospective case series study in 1999. The results of this study were reported in 2005 and this publication reports a continuation of this study with minor changes.

The researchers asked women with tumours at stages IB1, IB2 and IIA to take part, as well as selected women with stage IIB tumours. The study excluded women with certain high-risk conditions and severe morbid obesity.

All the women had MRI scans before surgery to look at how far the tumour had spread. Women whose tumour was larger than 5cm were given up to six courses of chemotherapy before surgery. The effect of chemotherapy was assessed, either clinically up to 2005 or using imaging scans after that time.

Women who had stage IB and IIA tumours were treated with TMMR regardless of how they responded to chemotherapy. Women with stage IIB tumours were eligible to receive TMMR if their tumours were not larger than 5cm or they had larger tumours that responded (shrank) to chemotherapy and no morbid obesity or evidence that the tumour had spread to the bladder wall or rectum.

Eligible women received TMMR surgery, which included taking slices of pelvic lymph node tissue to check for spread of the tumour. If spread was identified in these lymph nodes then more distant lymph nodes (those surrounding the aorta) were also checked for tumour spread. The areas surrounding the edge of the removed tissue were also checked to see if the entire tumour had been removed.

Women started urination training five days after surgery, with their catheter removed if the bladder was emptying satisfactorily (50ml or less residual urine volume). From 2006, patients whose tumour had spread to two or more lymph nodes were given up to six three-week cycles of chemotherapy after surgery.

Patients were followed up every three months for two years and then every six months. The researchers assessed whether the women experienced complications of surgery, a relapse or death (either due to the cancer or another cause). The researchers then calculated how long the women lived without a relapse and how long they lived overall.

What were the results of the study?

Between 1999 and 2008, the researchers performed the TMMR operation on 212 women. Of these women:

  • 112 had stage IB1 tumours,
  • 29 had stage IB2 tumours,
  • 18 had stage IIA tumours, and
  • 53 had stage IIB tumours.

The operation successfully removed the Müllerian compartment in all women. In five women, the tumour was assumed to have spread outside this compartment, based on what the surgeons saw during surgery, and therefore extra tissue was removed in these cases (bladder tissue in three women, ureter tissue in one woman and rectal tissue in two women). Fifty women whose tumour had spread to the pelvic lymph nodes had extra lymph nodes removed.

On average (median), the women were followed for 41 months after surgery (range 5 months to 110 months). One hundred and thirty two women (62%) experienced no complications of the surgery, 74 women (35%) had grade 1 complications (the least severe complications), 20 women (9%) had grade 2 complications (moderately severe complications) and none had the most severe grades of complications (grades 3 or 4).

Three women (1.4%) had tumour recurrence in the pelvis only, and in two of these women, recurrences were found in more than one area. All had further “salvage” treatment and were alive at the final follow-up five to seven years later.

Two women (1.1%) developed recurrences inside and outside the pelvis, and five women (2.4%) had recurrences outside the pelvis only. Five women (2.4%) died of cervical cancer and one (0.5%) died of metastatic secondary cancer. 

Five years after surgery, 94% of the women were alive without recurrence of the disease and 96% of them were alive (with or without recurrence).

What interpretations did the researchers draw from these results?

The researchers concluded that TMMR without post-surgical radiation “has great potential to improve the effectiveness of surgical treatment of early-stage cervical cancer”. They suggest that TMMR without radiotherapy “has the potential to improve survival by 15–20%”. They say that “further evaluation with multi-institutional controlled trials is now needed”.

What does the NHS Knowledge Service make of this study?

This study reports the development of an adapted surgical technique for early-stage cervical cancer at one surgical centre. The results have demonstrated low rates of cancer recurrence and a high five-year survival rate following treatment with TMMR.

Other potential benefits of this technique are that it does not standardly involve the removal of surrounding pelvic tissues, and that it avoids the use of radiotherapy. This means that patients could avoid the unpleasant side effects of radiation-based therapies and that the procedure carries only a low risk of damage to the nerve supply of the bladder, bowel and vagina. 

While this new technique appears to have potential, the main limitation of this study is that it did not have a control group. Therefore, it is not possible to say for certain how this surgery compares to radical hysterectomy or any other treatment option in terms of its benefits and risks. As the authors correctly conclude, (preferably randomised) controlled studies are needed to compare the TMMR procedure with other treatments.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Cervical cancer 'surgery boost'.

BBC News, 2 June 2009

Links to the science

Hockel M, Horn LC, Manthey N et al.

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

Lancet Oncology (early online publication), June 1 2009