4.2 Treatment options

4.2 Treatment options

Broadly for oesophageal cancer:

  • Some mucosal disease might be considered for surgery alone (e.g. T1b). Radiation therapy may be appropriate when surgery is not suitable.
  • Mucosal cancer (T1a) should be considered for endoscopic therapy. Submucosal disease (T1b No) should be considered for surgery alone.
  • Locally advanced disease (stage II or III) should be considered for multimodal treatment with neoadjuvant therapy (chemotherapy or chemoradiation) followed by surgery. Definitive chemoradiotherapy may be appropriate when surgery is not suitable.
  • Metastatic disease (stage IV) should be treated with palliative intent with systemic anticancer therapy, palliative intent radiotherapy and/or oesophageal stent placement (palliative oesophageal resection is not recommended).

Broadly for gastric cancer:

  • Some mucosal disease would typically be considered for surgery alone.
  • Mucosal cancer (T1a) should be considered for endoscopic therapy. Submucosal disease (T1b N0) should be considered for surgery alone.
  • Locally advanced disease (stage II or III) should be considered for perioperative chemotherapy and surgery.
  • Metastatic disease (stage IV) should be treated with palliative intent with systemic anticancer therapy and/or palliative intent radiotherapy

In the oesophagus, endoscopic therapies can be used for high-grade dysplasia and selected cases of early cancer (T1a) as a less morbid and potentially equally effective treatment option in comparison with oesophagectomy (Cancer Council Australia Barrett’s Oesophagus and Early Oesophageal Adenocarcinoma Working Party 2014; Uedo et al. 2012).

Endoscopic en-bloc resection is recommended for superficial oesophageal SCCs, excluding those with obvious deep submucosal involvement. Endoscopic mucosal resection may be considered in lesions smaller than 10 mm if en-bloc resection can be assured (Pimentel-Nunes et al. 2015). However, endoscopic submucosal dissection is recommended as the first option for mucosal SCCs larger than 10 mm in size, mainly to provide an en-bloc resection for accurate pathology staging and to avoid missing important histological features (Pimentel-Nunes et al. 2015).

Submucosal invasion caries an increased risk of lymph node metastasis and the need for further management should be discussed in an MDM (Draganov et al. 2019; Pimentel-Nunes et al. 2015; Rizvi et al. 2017).

In Barrett’s oesophagus, complete resection (R0) of a superficial lesion with mucosal adenocarcinoma is considered curative (Pimentel-Nunes et al. 2015). Complete resection (R0) of a sm1 lesion (≤ 500 μm) with a low risk profile (well or moderately differentiated, no lymphovascular invasion) is potentially curative but can also be associated with a risk of lymph node metastasis. This should be discussed in an MDM where the risk of surgery should be balanced against the risk of lymph node metastasis (Pimentel-Nunes et al. 2015).

Surgery for Barrett’s oesophagus is recommended in the following instances:

  • lymphovascular invasion
  • poorly differentiated tumour
  • deeper infiltration into sm1 and beyond (> 500 μm), or
  • where positive deep resection margins are diagnosed. If only the lateral margin is positive or there is piecemeal resection with no other high-risk criteria, endoscopic surveillance/re-treatment is recommended rather than surgery (Pimentel-Nunes et al. 2015).

For oesophageal cancers, following endoscopic resection the remaining Barrett’s mucosa should be eradicated (Cancer Council Australia Barrett’s Oesophagus and Early Oesophageal Adenocarcinoma Working Party 2014). Further treatment to the remaining non-dysplastic epithelium is necessary using either the endoscopic mucosal resection technique or radiofrequency ablation.

Endoscopic treatment is also feasible for selected high-grade dysplasia of the stomach and early gastric cancers confined to the mucosa (T1a). Not dissimilar to the oesophagus, there are two sets of indications for endoscopic management in the stomach: an absolute set of criteria and an expanded criteria. In relation to the absolute indications, the tumour must meet all the following criteria:

  • well-differentiated adenocarcinoma
  • no ulceration
  • stage T1a
  • have a diameter of less than 2 cm (Rizvi et al. 2017).

The expanded criteria has been modified to account for tumours that have a very low probability of lymph node metastasis. This includes tumours clinically diagnosed as T1a and are:

  • well-differentiated type without ulceration, however, greater than 2 cm in diameter
  • differentiated type with ulceration and less than 3 cm in diameter, or
  • undifferentiated type without ulceration and less than 2 cm in diameter (Rizvi et al. 2017).

Tumours extending up to 500 μm into the submucosa can also be considered. The risk of lymph node metastasis when endoscopic submucosal dissection is performed for the expanded indication is higher than when it is performed for absolute indications but remains low and should be balanced against the risks versus benefits of surgical resection (Draganov et al. 2019; Ono et al. 2016; Pimentel-Nunes et al. 2015; Rizvi et al. 2017).

Surgical resection offers the best long-term survival chance in patients with locally advanced oesophageal or gastric cancer.

Palliative oesophageal resection for metastatic cancer is not recommended.

Timeframe for starting treatment

Treatment should begin within two weeks of the MDM. Surgery should be scheduled when appropriate to the overall treatment plan.

Training and experience required of the appropriate specialists

Surgeon (Fellow of the Royal Australasian College of Surgeons [FRACS] or equivalent) with additional training and experience in oesophagogastric surgery, and with institutional credentialing and agreed scope of practice within this area.

Documented evidence of the surgeon’s training and experience, including their specific (sub-specialty) experience with oesophagogastric cancer surgery and procedures to be undertaken, should be available.

There is strong evidence, including published studies from Australia, that higher volume hospitals (defined as performing at least six oesophagectomies per year) have better clinical outcomes following oesophageal cancer surgery (Davis et al. 2018; Meng et al. 2019; Narendra et al. 2019; Ross et al. 2014).There is also strong evidence internationally that high-volume hospitals have better outcomes for gastric cancer.

International evidence suggests that surgeons who undertake a higher volume of resections have better clinical outcomes for complex cancer surgery such as oesophagogastric resections, although institutional volume is likely to be a more important factor than the individual surgeon (Gruen et al. 2009; Killeen et al. 2005). Patients undergoing oesophagogastric cancer surgery should be treated at specialist centres that have teams that deliver integrated expertise in endoscopy, imaging, interventional radiology, surgery and histopathology, and treat a high volume of these cases. Centres that do not meet this criteria should routinely refer cases to a centre with experience in that type of case.

Health service unit characteristics

To provide safe and quality care for patients having surgery, health services should have these features:

  • appropriate ward staff including nursing, dietetics, physiotherapy, occupational therapy and theatre resources to manage complex surgery
  • 24-hour medical staff availability
  • 24-hour operating room access
  • an intensive care unit with nursing and medical staff who are familiar with oesophagogastric surgery
  • 24-hour access to interventional radiology fully supported by other surgical specialties
  • specialist anaesthetists (Narendra et al. 2019)
  • diagnostic imaging and interventional radiology
  • pathology
  • nuclear medicine imaging
  • advanced endoscopy services.

Each unit performing complex oesophagogastric cancer surgery must demonstrate robust audit processes, and benchmarking of outcomes, to ensure quality outcomes are delivered consistently.

For oesophageal or oesophagogastric junction cancer, radiation therapy may be indicated as part of:

  • neoadjuvant therapy before surgery
  • definitive chemoradiotherapy for locally advanced disease in patients who are not able to undergo surgery (e.g. medical comorbidity or patient choice)
  • palliation in symptomatic individuals with advanced or metastatic disease such as dysphagia, pain and bleeding in advanced oesophagogastric cancer.

For gastric cancer, radiation therapy may be indicated:

  • postoperatively in combination with chemotherapy in selected patients who have undergone a gastrectomy for locally advanced gastric cancer
  • in the palliative setting, before or after chemotherapy for palliation of symptoms.

Timeframes for starting treatment

Treatment should begin within two weeks of the MDM.

Training and experience required of the appropriate specialists

Radiation oncologist (Fellow of the Royal Australian and New Zealand College of Radiologists [FRANZCR] or equivalent) with adequate training and experience with an agreed scope of practice within this area.

The training and experience of the radiation oncologist should be documented.

Health service unit characteristics

To provide safe and quality care for patients having radiation therapy, health services should have these features:

  • linear accelerator (LINAC) capable of image-guided radiation therapy (IGRT)
  • dedicated CT planning
  • access to MRI and PET imaging
  • automatic record-verify of all radiation treatments delivered
  • a treatment planning system
  • trained medical physicists, radiation therapists and nurses with radiation therapy experience
  • coordination for combined therapy with systemic therapy, especially where facilities are not co-located
  • participation in Australian Clinical Dosimetry Service audits
  • an incident management system linked with a quality management system.

For locally advanced oesophageal or gastric cancer, neoadjuvant chemotherapy with or without radiation therapy followed by surgery is recommended.

For locally advanced oesophageal or gastric cancer, perioperative chemotherapy or neoadjuvant chemoradiation followed by surgery are reasonable approaches.

For locally advanced gastric cancer, perioperative chemotherapy in patients undergoing surgery is the current standard of care. In select cases where patients have had upfront curative surgical resection, adjuvant chemotherapy or adjuvant chemoradiation can be considered.

For inoperable locally advanced oesophageal or gastro-oesophageal cancer, concurrent definitive chemoradiation is the current standard of care.

For patients with metastatic or inoperable locally advanced disease for palliative intent, systemic therapy alone is recommended:

  • chemotherapy plus trastuzumab for patients with HER2-positive advanced/metastatic adenocarcinoma of the stomach
  • chemotherapy alone in HER2-ve oesophageal/gastro-oesophageal or gastric cancer.

Current evidence supports using palliative radiation and chemotherapy sequentially rather than concurrently and is dictated by the predominant symptom requiring palliation as a priority.

Timeframes for starting treatment

Treatment should begin within two weeks of the MDM.

Training and experience required of the appropriate specialists

Medical oncologists must have training and experience of this standard:

  • Fellow of the Royal Australian College of Physicians (or equivalent)
  • adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).

Cancer nurses should have accredited training in these areas:

  • anti-cancer treatment administration
  • specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
  • the handling and disposal of cytotoxic waste (ACSQHC 2020).

Systemic therapy should be prepared by a pharmacist whose background includes this experience:

  • adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.

In a setting where no medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.

The training and experience of the appropriate specialist should be documented.

Health service characteristics

To provide safe and quality care for patients having systemic therapy, health services should have these features:

  • a clearly defined path to emergency care and advice after hours
  • access to diagnostic pathology including basic haematology and biochemistry, and imaging
  • cytotoxic drugs prepared in a pharmacy with appropriate facilities
  • occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019)
  • guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
  • coordination for combined therapy with radiation therapy, especially where facilities are not co-located
  • appropriate molecular pathology access

Patients with symptomatic locally advanced or recurrent oesophagogastric cancer should be assessed for chemoradiation, radiotherapy alone or systemic chemotherapy. Radiotherapy is an effective and well-tolerated modality for treating dysphagia. Where radiotherapy is not appropriate, endoscopic placement of a stent should be considered.

Patients with inoperable, locally advanced or metastatic oesophagogastric/gastric cancer should be assessed for palliative chemotherapy. In some patients with gastric cancer, there may be a role for surgical palliation or endoscopic stent placement for distal gastric cancer.

Timeframes for starting treatment

Treatment should begin within two weeks of the MDM.

The role of targeted therapies and immunotherapies is evolving. Trastuzumab in combination with chemotherapy is currently the only targeted drug shown to improve survival over chemotherapy alone in a subset of patients with HER2-positive metastatic adenocarcinoma involving the stomach or gastro-oesophageal junction. A few randomised studies also suggest modest benefit from immunotherapy in later disease stages (Janjigian et al. 2018; Kang et al. 2017). Recent trials have demonstrated improvement in survival and fewer adverse effects with anti-PDL1 immunotherapy either as monotherapy or in combination with chemotherapy in patients with tumours that have high expression of programmed cell death ligand 1 (PD-L1), with a combined positive score (CPS) ≥ 10, or deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI) (Bristol Myers Squibb 2020; Tabernero et al. 2019). However, apart from trastuzumab, immunotherapy is currently not reimbursed by the Pharmaceutical Benefits Scheme, and where possible patients should be encouraged to enrol in clinical trials.