(Cochrane) Editorial - Finding time to make the right decision: using frozen section to inform intra-operative management of suspicious ovarian masses Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Tuesday, July 12, 2016

(Cochrane) Editorial - Finding time to make the right decision: using frozen section to inform intra-operative management of suspicious ovarian masses

Editorial - Cochrane Library


Finding time to make the right decision: using frozen section to inform intra-operative management of suspicious ovarian masses

Jo Morrison, Toby Lasserson
Ovarian cancer is the seventh most common cancer in women worldwide.[1] As with many cancers, poor survival rates are largely attributable to the late stage of presentation.[2] Women who present with a suspicious ovarian mass without obvious disease outside of the ovary usually require surgery for diagnosis and staging. Pre-operative biopsy is possible, but it would risk dissemination of disease otherwise confined to the ovary. Surgical removal of the mass is the only way to obtain a definitive result by histological examination. A new Cochrane Review provides crucial evidence on the accuracy of frozen section analysis, a rapid diagnostic test that can inform management decisions of suspicious ovarian mass during surgery.[3]

Normal histological diagnosis is a relatively slow process, requiring multiple samples and steps for analysis. Known as a paraffin section, tissue samples are fixed with formalin and embedded in paraffin before being finely sliced, applied to slides, de-waxed and stained with dyes and antibodies before being examined under a microscope.

Many women undergoing surgical staging may in fact be being exposed to unnecessary risk. In a recent randomized controlled trial of screening for ovarian cancer, only one in three women having surgery for suspicious findings actually had ovarian cancer.[4] Identifying cancerous tumours and staging them accurately helps to guide decisions over further management, but should be balanced against avoiding unnecessary surgical procedures.

Frozen section analysis allows for a 'quick and dirty' assessment of the tumour. Samples are taken during the operation and snap frozen. They are cut into slightly thicker slices in a refrigerated tissue slicer. A result can be available within 20 to 30 minutes, meaning that decisions over the requirement for further surgery can be made there and then. However, speed comes at a price. Although results are available during the operation, they may not be as accurate for borderline tumours. The lack of fine structure preservation, the thicker slices, and limited sampling of the tumour means that paraffin section is still a more conclusive test.

While frozen section is not completely accurate, it is accurate enough to help intraoperative decision-making and could reduce the extent of surgery for a number of women ultimately found to have a benign ovarian mass. Ratnavelu and co-workers estimated that if frozen section was used to separate benign from borderline/malignant tumours, 280 women out of 1000 would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without, and would not need, additional procedures.[3] However, 85 women would have the diagnosis changed once final paraffin section histology was available postoperatively; 75 women would be incorrectly diagnosed with a cancer (false positive) and 10 women with a cancer would be missed on frozen section (false negative). If frozen section was used to separate benign/borderline tumours from cancer 261 women out of 1000 would have received a correct diagnosis of a cancer and 706 women would be correctly diagnosed without a cancer. Four women would be incorrectly diagnosed as having a cancer intraoperatively and subsequently found not to have a cancer (false positive), and 29 women with cancer would be missed (false negative).

Borderline tumours behave somewhere between a benign tumour and a cancer: they can seed themselves within the abdominal cavity and grow on the surface of other tissues, but they have not ‘learnt’ how to invade other tissues. Borderline tumours recur in approximately 1 in 20 women, often after a long time (sometimes over 20 years), but they do not require chemotherapy. Surgical staging for borderline tumours does not require removal of pelvic and para-aortic lymph nodes but ideally will involve sampling of peritoneum and omentum.

Frozen section is unlikely to replace paraffin section for final diagnosis, but this recent Cochrane Review demonstrates that it can usefully differentiate benign tumours from those that need further staging samples at the time of surgery.[3]
Frozen section can be helpful to tailor intra-operative management and can prevent many women undergoing unnecessary procedures to remove lymph nodes. This reduces the risk of perioperative complications and the long-term risk of removing lymph nodes, including swelling of lower limbs and collections of lymph fluid in the abdomen.

One driver for intraoperative staging is based on previous data that suggested that women with early ovarian cancer who were inadequately staged should be offered chemotherapy to reduce the risk of recurrence.[5,6] These data were based on a five-year follow-up, but data from 10-year follow-up has been incorporated into a recently updated Cochrane Review.[7] Combined data from all women with early-stage ovarian cancer shows a higher rate of survival with postoperative chemotherapy. The number of women needed to treat for an additional beneficial outcome (NNTB) to prevent one death within 10 years was approximately 13 (95% confidence interval 8 to 51). The review authors also analysed 'deaths from ovarian cancer' at 10 years using data from the ACTION and ICON1 trials.[5,8] This suggested that the difference in deaths from ovarian cancer between optimally and non-optimally staged patients was not statistically significant. It should be noted that few of the women in the study had low-risk stage Ia disease, so these data may not be applicable to this group, but the analysis provides a controversial and intriguing challenge to a long-held surgical 'certainty' that optimal staging with full lymphadenectomy is vital and that women not optimally staged should be offered additional surgery. It certainly adds weight to any technique, such as frozen section, that can reduce the risk of complications and unnecessary surgery for the majority of women who do not have even a potential benefit.
Jo Morrison1, Toby Lasserson2
1Consultant in Gynaecological Oncology, Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust, Taunton, UK; Co-ordinating Editor, Cochrane Gynaecological, Neuro-Oncology and Orphan Cancers Group; jo.morrison1@nhs.net
2Senior Editor, Cochrane Editorial Unit, Cochrane, London, UK; tlasserson@cochrane.org


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