Nasopharyngeal carcinoma management: Advances and hope
Nasopharyngeal carcinoma (NPC) is a difficult-to-treat malignancy due to its proximity to critical structures. It was once the fourth most common cancer in Hong Kong.1 Now, it is one of the most successful stories in oncology as the cancer has become much less prevalent and less lethal over the years.2 The number of new NPC cases has been reduced by approximately 70% since 1980, and the cancer-specific survival rate has been increasing due to treatment improvement.2 In a recent interview with Omnihealth Practice, Professor Lee, Wing-Mui Anne shared her insights on the current practice and the future of managing NPC.
Facts about NPC
NPC has a very skewed distribution with the highest incidence in southern China. It was the fourth most common cancer in Hong Kong in the past.1 Since 1980, the incidence of NPC has shown a steady decrease with the number of new cases decreased by 70% over the past 30 years (Figure 1).2 With advances in treatment, the survival rate of NPC patients has been increasing. Even for patients with extensive loco-regional involvement, 8-year overall survival above 50% can now be achieved.3 Currently, NPC is no longer the top 10 most leading cause of cancer deaths in Hong Kong.4
The exact cause of NPC is not fully understood, yet available knowledge points to the combination of genetic predisposition, environmental carcinogens, and the Epstein-Barr virus (EBV) as the cause of malignant changes, with resultant high prevalence especially among Southern Chinese population.5 As the pioneer in the field of NPC, Professor John HC Ho proposed that the volatile nitrosamines in salted preserved fish, a staple dish in the Cantonese cuisine, could be the culprit for NPC.5 This prompted the Hong Kong Anti-Cancer Society to initiate public education on reducing salted fish consumption, increasing the intake of vegetables, and promoting smoking cessation. As a result, Hong Kong is the first to report gratifying decrease in both NPC incidence and mortality.6
Risk communication is key to the radiation therapy planning
Radiotherapy is the key modality for treating NPC, with addition of chemotherapy recommended for loco-regionally advanced cases.7 Yet, radiotherapy is challenging especially for patients with extensive tumor infiltration into neurological structures surrounding the nasopharynx. Clinicians face the dilemma of using a high cancer-killing dose which could help control the cancer and lower the risk of recurrence but simultaneously incurs a higher risk of damage to normal tissues, some of which can be debilitating. A recent guideline contributed by more than 20 top international experts has provided clinicians with practical references for radiotherapy planning.8 It is recommended that final decisions of radiation therapy planning in NPC patients should consider the individual clinical situation and patients’ acceptance of the optimal balance of risk.8 It is essential for clinicians to explain the disastrous risk of not having radiotherapy due to the fear of toxicities, because uncontrolled cancer can cause far more organ destruction and is invariably lethal. Hence, optimal decision for radiotherapy in NPC requires a careful consideration of the risks and patients’ acceptance.
Induction and adjuvant chemotherapy
NPC is not only a locally destructive cancer but also has a high risk of disseminating to the rest of the body, such as the lymph nodes and distant organs. However, radiotherapy only targets the localized cancer and the addition of systemic treatment to kill disseminated cancer cells is needed.9 There is increasing evidence that concurrent-only chemotherapy may be inadequate, and significant survival benefit could be achieved with additional chemotherapy.9
One standard recommendation is to use concurrent chemoradiotherapy followed by adjuvant chemotherapy.9 However, as patients may experience discomfort and need time to recover after the completion of radiotherapy, it is definitely not easy to tolerate adjuvant chemotherapy. Clinicians should educate and encourage their patients to receive chemotherapy to maximize treatment effectiveness. The Hong Kong Nasopharyngeal Carcinoma Study Group had previously studied the usefulness of stratifying patients based on the EBV DNA test at the end of the radiotherapy to decide whether patients should receive chemotherapy.10 However, the result showed that patients with elevated EBV DNA had no significant difference in 5-year progression-free survival after receiving adjuvant chemotherapy or were placed on observation. Further research is needed to develop better risk stratification and more potent strategies for the worst prognostic group.10
Induction chemotherapy is another promising therapy option.11 Before the commencement of radiotherapy, most patients show good tolerance to chemotherapy. In addition, upfront administration of chemotherapy may achieve better distant control. Therefore, the current recommendation is to use induction chemotherapy followed by concurrent chemotherapy plus radiotherapy as the first option. For those who did not receive induction chemotherapy, concurrent chemoradiotherapy followed by adjuvant chemotherapy remains a suitable standard.
Factors to consider in managing recurrent NPC
In addition to gross tumor volume, other factors also play a significant role in the management of recurrent NPC. Firstly, a thorough whole-body check is required to ensure the absence of distant metastasis which is harbored by many recurrent NPC patients. If the tumor is still localized in the nasopharynx region, clinicians should first consider whether the tumor can be completely resected by surgery if expertise is available, as patients would have a higher risk of late toxicities if a second course of radiotherapy is used.
However, the majority of recurrence present with extensive involvement and radiotherapy is the only effective salvaging option. Clinicians should consider all factors, including patients’ toxicity due to the previous course of radiotherapy, in making the best possible treatment decision.
Good quality services during the COVID-19 pandemic
During the COVID-19 pandemic, many guidelines for surgery and radiotherapy have been published to guide clinicians to compromise the treatments. Ensuring the safety of healthcare workers and patients is most essential.12 With concerted efforts to provide a safe environment, treatment during COVID-19 does not have to be compromised.12 To achieve such environments, strategies of different levels are crucial.12 The government and regional authorities should develop policies to help screen patients with polymerase chain reaction (PCR) tests and ensure that infected and asymptomatic patients can be isolated to prevent cross-infection.12 On the hospital level, the administration needs to make the decision to prioritize clinical services.12
In the University of Hong Kong-Shenzhen Hospital, priority of treatment is given to services for which delayed management would be detrimental to the patients’ survival or quality of life such as obstetrics, oncology and emergency care.12 Patients with chance of cure are encouraged to proceed with radical treatment, and the therapies will be arranged with high vigilance and sufficient protective measures. Fortunately, our good service of radiotherapy was maintained and neither staff nor patients were infected in this testing period at the University of Hong Kong-Shenzhen Hospital.12
The future of NPC management
Immunotherapy is now mostly used in patients who have distant metastasis or extensive recurrent cancer which could not be treated with further irradiation.13 Immunotherapy is considered as second-line treatment for patients whose cancers progress after chemotherapy. However, with the current indication, the response rates are lower than 25% and few patients achieve complete remission.14 One key difficulty is the lack of available biomarkers to predict treatment response. More researches are ongoing to incorporate immunotherapy into NPC management as first-line treatment.
At the University of Hong Kong-Shenzhen Hospital, the service quality aligns with the standard set by the University of Hong Kong Health System to provide NPC patients with the state-of-the-art treatment. Currently, one of the treatment challenges for NPC in China stems from different drug approval systems. Some medications approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) still require additional approval from the Chinese National Medical Products Administration (NMPA) before the drug can be introduced for clinical usage. Although most of the common drugs needed for NPC are available in China, it is hoped that the Greater Bay Area policies would allow more and faster approvals of other novel drugs for treating the most challenging NPC cases in China.
Message to physicians and conclusion
NPC is one of the most difficult cancers to treat, and the key treatment by radiotherapy is one of the greatest challenges for oncologists. However, this is the most gratifying cancer to treat as the survival rate of NPC is increasing, even for patients who present with stage IV disease, with more than half of the patients being curable. In order to provide all optimal treatment options with the best survival benefits to NPC patients, to carefully consider all factors affecting the therapeutic ratio, to closely communicate with patients to understand their preferences, and to encourage them to persevere despite fear of toxicities are all very important. With more personalized treatment strategies based on the panel of refined prognostic factors and the development of novel therapeutic agents, the dream of controlling NPC can be realized in the future.
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