Tumor compartments: A ‘revolution’ in cancer surgery

Medical Tribune July 2009 SFIV
David Brill

A novel approach to treating cervical cancer may signal the end of the radical hysterectomy and could one day revolutionize the field of surgical oncology, says a pioneering team of German surgeons.

By removing only the embryologically defined ‘compartments’ in which tumors are most likely to spread, the surgeons can spare surrounding tissues and minimize collateral damage.

The technique reduces complications and recurrence rates, removes the need for radiotherapy, and could improve survival rates by as much as 20 percent compared to conventional hysterectomy, the group reported recently in The Lancet Oncology.

Research is already underway to extend the concept to vulvar and endometrial cancers, said lead researcher Professor Michael Höckel, chairman of the department of obstetrics and gynecology at the University of Leipzig, Germany.

“We have found that the tumor is confined for a long time in its natural course to a defined tissue compartment – it’s not like an explosion infiltrating all tissues around the tumor,” said Höckel.

“This new perspective in surgical anatomy enables you to see and operate on the tissue in which the tumor is spreading, irrespective of the tumor entity. This is a general principle which could really revolutionize surgical treatment for malignant disease,” he said.

The cervical cancer procedure – total mesometrial resection (TMMR) – targets only the non-distal part of the Müllerian compartment. Surgeons remove the proximal vagina, uterus and extra-cervical mesenchyme but spare nearby non-Müllerian tissues, including the nerves which supply the vagina, bladder and rectum.

Results from 212 women who underwent TMMR without radiotherapy at the University of Leipzig show an overall 5-year survival rate of 96 percent, and recurrence-free survival of 94 percent. The study was conducted prospectively from October 1999 to July 2008 on women with early-stage cancers: International Federation of Gynecology and Obstetrics (FIGO) stages IB, IIA and selected IIB. [Lancet Oncol 2009 May 29; Epub ahead of print]

Sixty two percent of procedures were complication-free at a median of 41 months’ follow-up; 35 percent of patients had grade one complications and 9 percent had grade two. Three patients had developed pelvic cancer recurrence, five developed distant recurrences, and two developed both pelvic and distant recurrence.

Höckel and colleagues developed the principle of TMMR by studying uterovaginal development in embryos and fetuses – enabling discrimination of tissue compartments on the basis of their embryological origin. Previous work showed that early cervical tumors grow largely along these lines. [Lancet Oncol 2005 Oct;6(10):751-6]

Singapore surgeon Adjunct Associate Professor Yam Kwai Lam said that he would be “open to any new technique” as long as it provided “substantial overall benefit to the patient.”

“The published results look impressive, but lacking in long-term survival data. In order for the technique to replace conventional hysterectomies, validation would require a large randomized controlled trial to provide the answer,” said Yam, head and senior consultant in the department of gynecological oncology at KK Women’s and Children’s Hospital.

Höckel has previously presented TMMR to surgeons in Southeast Asia – performing live demonstrations in Hong Kong in December 2006, and Bangkok in August 2008.

A multicenter trial is due to launch soon in Germany, with a view to comparing results of 200 TMMRs against 200 conventional hysterectomies. Publication is expected in around 4 years, said Höckel, who has not performed a standard hysterectomy since first developing TMMR some 10 years ago.

“The conventional techniques have no right to exist any longer because they are wrong. Now that we know how a tumor is spreading … it’s no longer acceptable to use these sub-prime concepts and techniques,” he said.