​Not only are primary care physicians crucial to screening and early detection of nasopharyngeal cancer, they can also play a key role throughout the patient journey – by helping their patients manage the side effects and comorbidities during treatment, as well as survivorship care to optimise outcomes.

NASOPHARYNGEAL CANCER

Nasopharyngeal cancer (NPC), commonly known as nose cancer, is a disease of particular interest to Singapore due to its high incidence and tendency to afflict people who are still in the economically active age.

NPC arises from the epithelium of the nasopharynx (also known as posterior nasal space). This small cuboidal space is located behind the nasal cavity and above the oropharynx. It has connections to the middle ear via the Eustachian tubes on both sides of the lateral walls.

EPIDEMIOLOGY

According to data from GLOBOCAN 2020, more than 130,000 new cases of NPC are diagnosed worldwide annually with the majority of cases occurring in South-East Asia, China and Northern Africa. Men are three times more commonly affected than women.

Although data from the Singapore Cancer Registry shows that the incidence of NPC has been gradually declining since the 1970s, the incidence of NPC in Singapore remains one of the highest in the world with 8.9 per 100,000 males affected per year.

While the reasons for this decline are unclear, it is believed that lifestyle changes due to rapid economic development are contributory. Most of the cases occur in the Chinese race, with peak incidence at the age of 50-59 years.

RISK FACTORS

Interaction of several factors increases the risk of NPC. These are:

• Epstein-Barr virus (EBV) infection
• Environmental factors (frequent consumption of salted and preserved foods, such as salted fish and vegetables, which are high in nitrosamines – carcinogenic compounds linked to NPC)
• Genetic predisposition – Patients with a family history of NPC, especially in first degree relatives, have an increased risk of developing NPC

SYMPTOMS AND SIGNS

In the early stage, patients with NPC may have little or no symptoms. Some patients may present with unilateral blocked ears that come and go, self-resolving blood-stained sputum and small neck nodes which are often attributed to upper respiratory tract infection.

This makes diagnosis of NPC in the early stage challenging. As a result, about three-quarters of patients with NPC have stage III or IV disease by the time they are finally diagnosed.

In general, it may be prudent to refer the patient to the otolaryngologist for an opinion if patients have persistent symptoms that last more than a month or are recurrent. Common symptoms and signs of NPC are listed in Table 1 below.

Table 1

Figure 1 Tumour in the post-nasal space extending into the fossa of Rosenmüller and abutting the posterior cushion of the Eustachian tube

Figure 2 Otitis media with effusion secondary to obstruction of the Eustachian tube opening in the post-nasal space

Photographs courtesy of Dr Constance Teo

SCREENING

The use of EBV serology (EBV VCA-IgA and EBV EAIgA) and plasma EBV DNA has been proposed as a screening test for NPC. However, there is no good evidence to date that routine mass screening (even in highly endemic populations) could improve the outcome of NPC in the general population.

In Singapore, the Report of the Screening Test Review Committee (2019) recommends the use of EBV serology in combination with nasopharyngoscopy for screening only in high-risk individuals (i.e., individuals with a first degree relative [e.g., parent or sibling] with NPC).

INVESTIGATIONS AND STAGING FOR NPC

Routine investigations

Several investigations are routinely performed to determine the stage of disease and fitness for treatment. These include:

• Biopsy of the nasopharyngeal mass seen on nasoendoscope is essential for the diagnosis of NPC. Undifferentiated carcinoma is the most common subtype seen in Singapore, and other less common histologies include keratinising squamous cell carcinoma and non-keratinising differentiated carcinoma.

• Full blood count and tests for renal function and liver function

• Hepatitis B screening is done for all patients due to endemicity, so that patients can be started on anti-viral treatment to prevent hepatitis B flare during chemotherapy.

• Plasma EBV DNA is a blood test that measures the viral load of EBV. This has been shown to be a predictive marker (i.e., patients with persistent EBV DNA detectable in the blood at the end of treatment have a poorer prognosis compared to patients with undetectable EBV DNA).

• MRI of nasopharynx and neck to determine local and nodal extent of disease

• FDG PET-CT has the highest sensitivity and specificity in excluding distal metastasis. Alternatively, CT chest abdomen and bone scan may be used if cost is a consideration.

• Baseline audiometry is performed as patients may develop hearing loss due to effects of treatment.

Staging

Once the scans are performed, the oncologist will ‘stage’ the disease. The staging system currently used is from the 8th edition of the American Joint Committee on Cancer (AJCC) staging system which uses a predefined combination of size and extent of the tumour, lymph nodes and presence of metastasis to determine the stage.

Stage distribution in 2017 from our cancer registry are as follows:

• Stage I: 7.3%
• Stage II: 17.5%
• Stage III: 25.2%
• Stage IV: 50%

It is important to note that stage IV is divided into two groups:

• Patients with stage IVA are those with locally advanced disease, but no spread to other parts of the body (i.e., still considered curable)
• Patients with stage IVB are those in which there is evidence of metastasis beyond the head and neck region (i.e., generally considered incurable)

TREATMENTS

1. Radiotherapy

The main treatment for NPC is radiotherapy, also known as radiation therapy. Radiotherapy uses powerful and targeted X-ray beams to cure cancer by causing double-strand DNA breaks in cancer cells. Typically, the treatment covers the nasopharynx (where the primary tumour sits) and the neck node regions (even if none are seen on scans due to high incidence of microscopic disease).

Patients undergoing radiation usually go for once-a-day treatment (approximately 20 minutes every weekday, with weekend breaks to recover from side effects) over seven weeks (typically 33 to 35 sessions).

2. Chemotherapy

Current evidence suggests that the addition of chemotherapy to radiation has a significant survival benefit for patients with stage III and IVA NPC, and some patients with stage II NPC.

Patients derive the most benefit when chemotherapy is given concurrently with radiation, but further chemotherapy either before or after radiation may be needed for some patients. The two commonly used chemotherapy agents in NPC are cisplatin and gemcitabine.

In patients with metastatic NPC, chemotherapy plays an important role to help palliate symptoms by controlling the growth of the cancer.

3. Surgery

Surgery is not a common treatment for NPC and is usually reserved for cases where the cancer recurs after initial treatment. In cases where there is a small cancer recurrence at the nasopharynx or in the lymph nodes of the neck, surgery may be considered to treat the recurrence. This may be performed either through open surgery or endoscopic (keyhole) surgery through the nose.

The GP’s Role in NPC Patient Care

MANAGING SIDE EFFECTS OF TREATMENT

Most patients undergoing treatment will experience some side effects. Radiation side effects are divided into acute effects (i.e., side effects that occur during radiation treatment) and late effects (i.e., side effects that manifest many months to years after completion of radiation).

The oncologist will monitor patients closely during treatment to manage side effects, but patients may still present to primary care if their symptoms are not better, especially if after-hours. Common side effects of radiotherapy and chemotherapy are listed in Table 2 below.

Table 2

WHAT GPs CAN LOOK OUT FOR IN NPC PATIENTS

There are a few considerations that a primary care physician should look out for, when a patient on active NPC treatment presents to the clinic (Table 3).

Table 3

PROGNOSIS OF NPC

The prognosis of NPC is generally very good. The reported five-year survival rates are:

• Stage I disease – 93%
• Stage II disease – 87%
• Stage III disease – 81%
• Stage IVA disease – 65%
• Stage IVB disease – 63%

FOLLOW-UP AND SURVIVORSHIP CARE

The oncologist will follow up with patients at regular intervals for a minimum of five years. During the consultations, patients are assessed for evidence of recurrence using clinical examinations and investigations. Long-term side effects, if any, are monitored and managed.

Primary care physicians play an important role in survivorship care. Some common issues that primary care physicians should pay attention to are listed in Table 4.

Table 4

CONCLUSION

NPC is not uncommon in Singapore. Primary care physicians play an important role in early detection of the cancer, managing comorbidities during treatment as well as looking after patients after the end of their treatment.

REFERENCES

1. Singapore Cancer Registry 50th Anniversary Monograph (1968 – 2017). Accessed from: https://nrdo.gov.sg/publications/cancer

2. GLOBOCAN 2020 Nasopharyngeal Cancer Fact Sheet. Accessed from: https://gco.iarc.fr/today/data/factsheets/cancers/4-Nasopharynx-factsheet.pdf

3. Report of the Screening Test Review Committee (2019). Accessed from: https://www.ams.edu.sg/view-pdf.aspx?file=media%5c4817_fi_59.pdf&ofile=STRC+Report+March+2019.pdf

Dr Soong Yoke Lim is a Senior Consultant Radiation Oncologist and Deputy Chair at the National Cancer Centre Singapore (NCCS). He sub-specialises in the radiotherapy management of patients with gynaecological and head and neck cancers. Dr Soong has an interest in cancer survivorship and is the medical advisor for the Nasopharyngeal Cancer Support Group at NCCS.

GPs can call the SingHealth Duke-NUS Head & Neck Centre for appointments at the following hotlines:

Singapore General Hospital: 6326 6060
Changi General Hospital: 6788 3003
Sengkang General Hospital: 6930 6000
KK Women’s and Children’s Hospital: 6692 2984
National Cancer Centre Singapore: 6436 8288
National Dental Centre Singapore: 6324 8798