Improving outcomes in ovarian and oesophageal cancer

Two New national clinical guidelines have been published to aid in the diagnosis, staging and treatment of patients with oesophageal or oesophagogastric junction (OGJ) cancer, and the diagnosis and staging of patients with ovarian cancer.

The guidelines, launched by Minister for Health Simon Harris in August, were developed by multidisciplinary groups supported by the HSE’s National Cancer Control Programme (NCCP) and quality assured by the Department of Health’s National Clinical Effectiveness Committee (NCEC). The ovarian guideline was co-chaired by Dr Josephine Barry, consultant radiologist at Cork University Hospital, and Dr Ciarán Ó Riain, consultant histopathologist, St James’s Hospital, Dublin. The oesophageal and oesophagogastric junction cancer guideline was chaired by Prof John Reynolds, upper gastrointestinal consultant surgeon, St James’s Hospital, Dublin.

The National Clinical Guidelines relating to cancer care are underpinned by recommendation 37 of the National Cancer Strategy 2017-2026, which places an emphasis on prevention, early diagnosis, treatment and quality of life.

Background

Ireland has one of the highest incidence rates of both ovarian and oesophageal cancer in Europe, with rates of 16.1 and 7.9 per 100,000 respectively, with the incidence of both ovarian and oesophageal cancers projected to rise.

Ovarian cancer was the fourth most common cause of cancer-related deaths among women in Ireland between 2013 and 2015, with an average of 269 deaths annually.¹ Ireland has one of the highest rates of ovarian cancer in Europe. Figures from the European Cancer Information System for 2018 estimate that in Ireland the incidence rate (European old age-standardised rate) of ovarian cancer is 16.1 per 100,000, compared with an average of 11.8 across the EU28.²

In the same period between 2013 and 2015, oesophageal cancer was the sixth most common cause of cancer-related deaths in Ireland, with an average of 387 deaths annually from 2013-2015.¹

The National Cancer Registry Ireland (NCRI) expects the impact of both diseases to grow exponentially over the coming decades, with cases of ovarian cancer projected to increase by 67-80% by 2045. A 103% increase in oesophageal cancer cases involving males is also projected, while cases involving females are projected to increase by 60%.

Ovarian cancer

The development of a new guideline for ovarian cancer was considered a priority as symptoms are often vague and early diagnosis is essential. As such, Diagnosis and staging of patients with ovarian cancer³ focuses solely on uncertain areas of clinical practice, where there is practice variation or where there is new or emerging evidence that may impact patient outcomes.

Dr Barry commented: “This document offers health professionals up to date guidelines for best practice in the diagnosis and staging of patients with suspected ovarian cancer and also focuses on genetic aspects of ovarian cancer”.

Dr Ciarán Ó Riain added: “Ovarian cancer may be the first indication of two of the most common inherited syndromes that predispose to development of a number of different cancer types. This guideline recommends offering appropriate subgroups of women testing for presence of a mutation in the BRCA gene. This provides an opportunity to engage in true shared decision making and offer patients an informed choice to manage their own health risks according to their wishes and values. It provides us with an opportunity to take a visionary approach to the health of women with ovarian cancer and their families.”

The new ovarian cancer guideline makes a number of recommendations in the context of the following specialties:

• Radiology
• Pathology
• Genetics.

Radiology

Where ovarian carcinoma is suspected, a combination of transabdominal and transvaginal ultrasound should be performed and the results interpreted using the International Ovarian Tumour Analysis in conjunction with clinical assessment (quality of evidence: high; strength of recommendation: strong).

MRI is the recommended imaging modality where a patient has an indeterminate ovarian mass (quality of evidence: moderate; strength of recommendation: strong).

A CT of the thorax, abdomen and pelvis with oral and intravenous contrast should be carried out for the staging of ovarian cancer (quality of evidence: low; strength of recommendation: strong) but if the CT is indeterminate, the patient’s condition should be discussed further at a multidisciplinary team meeting (quality of evidence: low; strength of recommendation: weak).

If a patient has a high suspicion of relapse, a CT of the thorax, abdomen and pelvis is recommended as the first choice imaging test. If the CT does not indicate recurrence, a PET-CT is recommended (quality of evidence: high; strength of recommendation: strong).

Pathology

Tubo-ovarian cancer should be diagnosed by histological examination of tissue sample, allowing for sub-typing by morphology and immunohistochemistry. Failing this, a cytological specimen should suffice. Clinical, radiological, pathological and cytological findings should be factored into any decision relating to treatment (quality of evidence: low; strength of recommendation: strong).

Complex immunohistochemistry marker testing, if required, should be performed at the appropriate specialist laboratory (quality of evidence: high; strength of recommendation: strong).

Genetics

Germline mutation testing appropriate to sub-type should be offered to patients with tubo-ovarian carcinoma (quality of evidence: moderate; strength of recommendation: strong).

It is recommended that patients with tubo-ovarian carcinoma with a test result that shows a pathogenic variant or variant of uncertain significance be offered post-test counselling. If a family history is present, referral to genetic services may be necessary (quality of evidence: low; strength of recommendation: weak).

All women with an endometrioid or clear cell carcinoma diagnosis should undergo mismatch repair protein testing by immunohistochemistry, regardless of age (quality of evidence: low; strength of recommendation: weak).

Oesophageal cancer

The incidence of oesophageal cancer has markedly increased in Ireland and the Western World, with obesity, tobacco, and severe acid reflux the main predisposing factors, according to Prof Reynolds. 

“A diagnosis of oesophageal cancer is greatly feared, as it commonly presents at a late stage, and treatment, in particular surgery, is a major complex undertaking,” he said, pointing out that the new guideline – Diagnosis, staging and treatment of patients with oesophageal or oesophagogastric junction cancer⁴ – represents a major multidisciplinary undertaking by the NCCP between oesophageal specialists and patient representatives. 

It details advances in staging, diagnosis, and treatment that define and underpin a modern standard of care across all designated Centres in Ireland. 

“Encouragingly, the guidelines highlight recent significant advances in prevention, early diagnosis and treatment that provide real optimism for improved cure rates,” Prof Reynolds said.

The new oesophageal/OGJ guideline makes a number of recommendations in the context of the following specialties:

• Radiology
• Pathology
• Surgery and gastroenterology
• Palliative care.

Radiology

In patients with early-stage oesophageal/OGJ cancer, an oesophagogastro duodenoscopy (OGD) is recommended, plus a diagnostic CT followed by an endoscopic ultrasound (EUS) (grade of recommendation based on quality of evidence: B).

In early-stage patients who have had an OGD, diagnostic CT and EUS, a PET-CT should be considered following discussion at a multidisciplinary team meeting (grade of recommendation: C).

Patients in the advanced stage of oesophageal/OGJ cancer should undergo an OGD and a diagnostic CT (grade of recommendation: B).

If no metastatic disease is identified in the CT, a PET-CT is recommended. Further evaluation with an EUS is necessary if no metastatic disease is identified in the PET-CT. If metastatic disease is identified in the CT, there is generally no need for further imaging (grade of recommendation: B).

Pathology

Practitioners should refer to the American Joint Committee on Cancer (AJCC) 8th edition for pathological staging. Standardised reporting using the current dataset guidelines published by the Royal College of Pathologists in the UK is also recommended (grade of recommendation: A).

Every lymph node identified should be examined (grade of recommendation: D).

In resected specimens, the distance from the tumour to the circumferential resection margin (CRM) should be stated in millimetres to one decimal point for optimal precision (grade of recommendation: B).

Surgery and gastroenterology

To determine whether a patient who has oesophageal/OGJ cancer is fit for surgery, a full clinical assessment should be performed. A multidisciplinary meeting should also be held and patients with symptoms of cardiac or respiratory disease should be assessed by the appropriate specialist (grade of recommendation: D).

A staging laparoscopy is recommended where a patient has locally advanced oesophageal adenocarcinoma involving the abdominal oesophagus or junction (grade of recommendation: B).

Where classification is concerned, OGJ tumours should be classified as type I (distal oesophagus), type II (cardia) and type III (proximal stomach) (grade of recommendation: C).

The surgeon’s operative strategy should focus on achieving adequate in vivo longitudinal and radial resection margins, with lymphadenectomy appropriate to tumour type and location. Type III OGJ tumours should be treated by transhiatal extended total gastrectomy and type II OGJ tumours by transiatal/transthoracic oesophagectomy or extended gastrectomy. In the case of a type I OGJ tumour, a transthoracic oesophagectomy is recommended, or a transhiatal oesophagectomy in selected cases (grade of recommendation: B).

Endoscopic resection should be considered the therapy of choice for neoplasia associated with visible lesions and T1a carcinoma in patients with early oesophageal/OGJ cancer (grade of recommendation: B).

Where flat high-grade dysplasia or intramucosal cancer are present after endoscopic resection, radiofrequency ablation is the recommended therapy (grade of recommendation: A).

Squamous cell neoplasia (superficial lesions) should be treated with endoscopic resection in patients with early oesophageal/OGJ cancer (grade of recommendation: C).

Radiofrequency ablation is not advised in western populations for the treatment of squamous cell neoplasia in early-stage patients (grade of recommendation: D).

In patients with locally advanced oesophageal cancer, transthoracic oesophagectomy is recommended. However transhiatal oesophagectomy can be considered in patients with high operative risk as this procedure has reduced morbidity compared to transthoracic oesophagectomy (grade of recommendation: A).

A transhiatal approach can also be considered in patients with OGJ tumours that can be resected with radial resection margins and a lower mediastinal and nodal dissection (grade of recommendation: B).

Where positive lymph nodes are present in patients with locally advanced oesophageal cancer, transthoracic oesophagectomy may be of benefit (grade of recommendation: B).

The guideline states that all surgical approaches can be considered but that there are advantages to opting for minimally invasive surgery, particularly with respect to pulmonary morbidity. However there is no evidence, according to the guideline, of superiority of minimally invasive procedures on oncological outcomes.

The guideline also recommends the use of enhanced recovery after surgery programmes in order to improve the patient’s chance of survival and reduce the length of hospital stay.

The guideline also states that all oesophageal/OGJ surgery should be subject to input by a multidisciplinary team and performed by a surgeon in a designated, regularly audited cancer centre.

Palliative care

Early provision of palliative care can improve patient outcomes (grade of recommendation: C).

Palliative care should be provided throughout the course of the illness and the patient’s palliative care needs should be assessed on an ongoing basis (grade of recommendation: D).

Resources

Both National Clinical Guidelines, as well as a summary of the oesophageal/OGJ cancer guideline, are available in full at
www.health.gov.ie

References

1. National Cancer Registry Ireland (NCRI) 2018b. Cancer in Ireland 1994-2016 with estimates for 2016-2018: Annual report of the National Cancer Registry. NCR, Cork, Ireland
2. European Cancer Information System (ECIS). 2018. Available: https://ecis.jrc.ec.europa.eu [Accessed July 2018]
3. Department of Health. Diagnosis and staging of patients with ovarian cancer: National Clinical Guideline No. 20, August 2019. Available on the Department of Health website www.health.gov.ie
4. Department of Health. Diagnosis, staging and treatment of patients with oesophageal or oesophagogastric junction cancer, National Clinical Guideline No. 19, August 2019. Available on the Department of Health website www.health.gov.ie