The unmet need of lung cancer therapy in Nepal

Lung cancer is the most frequently diagnosed cancer worldwide (12.4% of all cancers) and the leading cause of cancer-related deaths. Cases are often diagnosed when the cancer has already spread to an advanced and non-curable stage, translating into the lowest five-year survival rates.[1] According to a recent analysis from the population-based cancer registry (PBCR), one in 14 men and one in 13 women in Nepal are at risk of developing cancer before the age of 75, with the highest risk being found for lung cancer (one in 80).[2] Similar to global trends, lung cancer is the most common cancer in Nepal (12.3% of all cancers) and accounts for the highest mortality in both men and women (20.8%). Notably, more women from rural regions (22.2%) suffer from lung cancer compared to women from urban regions (11.3%).[2] The age-standardized incidence rates in Nepal increased by 12.7% from 1990-2019, contributing to the loss of 45,200 disability-adjusted life-years (DALYs) in 2019 alone.[3] Hence, there is a significant burden of lung cancer in Nepal, and there is an unmet need for optimizing screening, research, and access to diagnostics and treatment facilities in the country. Most of the data on patients with cancer in Nepal come from hospital-based cancer registries (HBCRs), which were established in 2003. Population-based cancer registries began in 2018, meaning the true magnitude of the lung cancer burden in Nepal may be underestimated.[4] Parikh et al.[5] estimated that new cases across India might be more than two times of Global Cancer Observatory (GLOBOCAN) estimates, extrapolating data from the Indian Cancer Society’s PBCR in a single state. Similarly, Nepal may be facing a much larger lung cancer burden than currently recognized, with more comprehensive data needed to confirm this suspicion. In the study by Yadav et al.,[6] published in the current issue of the Cancer Research, Statistics and Treatment journal, the authors elucidated the clinicopathological characteristics of 192 patients with lung cancer who presented to a single institution in Nepal between January 2020 and December 2023. The study noted that 75.5% (145) of patients had non-small-cell lung cancer (NSCLC), while 5.7% (11) had small-cell lung cancer (SCLC). Nearly 20% (36) of patients were placed in the “others/not defined” category. Most patients (186) had advanced disease at diagnosis: 56.8% at Stage IV and 40.1% at Stage III, with only 3% (6) presented at Stage I/II. Among the patients, 2% (4) underwent surgery, 66% (126) received chemotherapy, and 54% (104) received radiation therapy. Only 8% (15) of patients received targeted therapy, and a dismal 1% (2) of patients received immunotherapy.[6] Piya[7] published data on 250 patients with lung cancer from a single institution in Nepal in 2019. Five years later, there seem to be notable differences between the two data sets. In 2019, the majority of patients were male (85.6%), and 80% of them were smokers.[7] In the present study, however, the proportion of male patients (45%) is nearly equal to female patients (55%), and the percentage of smokers has significantly decreased (68% were non-smokers).[6] In 2019, squamous cell carcinoma was more common (51.2%) than adenocarcinoma (26.8%).[7] In contrast, the current study reports adenocarcinoma as the most frequently diagnosed subtype (45%), followed by squamous cell carcinoma (32%).[6] A similar declining trend in small-cell-carcinomas was also observed, dropping from 22% in the study by Piya to 5.7% in the present study. This reflects the global trend, where adenocarcinoma is the most common subtype of lung cancer as of 2020.[6-8] We commend the authors for shedding light on the current epidemiology and treatment trends of patients with lung cancer in this snapshot.[6] This data also highlights various unmet needs that must be addressed on multiple levels. Access to healthcare facilities within 30 minutes of distance is available to only 61.8% of Nepalese households, with significantly better access in urban areas (85.9%) compared to rural areas (59%).[9] Even for patients with access and resources, diagnostic facilities such as positron emission tomography-computed tomography (PET-CT), endobronchial ultrasound (EBUS), mediastinoscopy, transthoracic CT-guided biopsies, immunohistochemistry (IHC), and molecular profiling (with polymerase chain reaction [PCR] or next-generation sequencing [NGS]) are limited.[4] The lack of routine availability of biopsy and IHC is reflected in the current study by Yadav et al.,[6] as 20% of patients were placed in the “others/not defined” category. A significant number of samples for IHC are processed by private laboratories and outsourced to India, leading to diagnostic delays due to longer turnaround times.[4] Physician-related factors also contribute to late diagnoses, as many patients with respiratory symptoms are treated empirically for chronic obstructive pulmonary disease (COPD) or with prolonged courses of antibiotics or anti-tubercular drugs (ATT) before a CT scan is performed or malignancy is considered. This is particularly true for middle-aged, never-smoking female patients.[10] Once diagnosed, there are further challenges in treatment. Nepal faces an unmet need for more medical oncologists, radiation oncologists, and onco-surgeons.[11] There is also a huge deficit in molecular testing in the country. The authors acknowledge this knowledge gap in their study.[6] The limited availability of NGS testing at a few centers and the high cost of molecular testing further compound the issue.[12] In Nepal, the incidence of mutations in the epidermal growth factor receptor (EGFR) gene varies from 29-36% and is comparable to that of India.[13-15] However, without proper molecular testing, a significant number of patients with lung cancer, particularly the 2/3rd who are non-smokers, may be undertreated with EGFR inhibitors and other molecularly targeted agents, leading to poorer outcomes. Batra et al.[16] analyzed the uptake of targeted therapy for various mutations in lung cancer cases detected by NGS and found that 65% of patients received targeted therapy for MET alterations, 83% for ROS1 rearrangements, 52% for RET rearrangements, 63% for BRAF V600E mutations, and 17.6% for ERBB2 mutations. Additionally, 75% of patients received EGFR-directed therapy, and 79% received ALK inhibitors. In comparison, only 8% of patients in the study by Yadav et al.[6] received targeted therapy, highlighting the urgent need to make these tests and treatments more accessible. Even with improved molecular target detection, treatment hurdles remain due to limited drug availability, lack of universal health coverage by the government, and the absence of robust patient support programs from pharmaceutical companies.[4] Similarly, cost becomes a major deterrent, particularly for immunotherapy, and sadly, only 1% of the patients could receive life-prolonging immunotherapy as noted by Yadav et al.[6] There is no formal lung cancer screening program in Nepal. As noted in the accompanying article, more than 95% of patients presented to the hospitals with advanced-stage disease.[6] In light of successful lung cancer screening programs in other countries and evidence showing improvement in lung cancer survival rates with low-dose CT screening (National Lung Cancer Screening Trial and the Dutch-Belgian NELSON trial), establishing a nationwide screening program is a need of the hour.[17-19] Pending the venture, it is important to initiate educational programs at both public and hospital levels to raise awareness about the benefits of early detection and screening. Globally, mortality from lung cancer has been declining due to advancements in screening, early detection, and treatment with targeted therapies and immunotherapy.[20] Howlader et al.[21] reported a 6.3% annual decrease in incidence-based mortality from NSCLC between 2013 and 2016. Furthermore, the “State of Lung Cancer” report for 2024 highlighted a 26% increase in the five-year survival rate, now at 28.4%, among patients with lung cancer in the United States.[22] However, most of the available data may not reflect the reality in low- and middle-income countries (LMIC) like Nepal, where lung cancer mortality trends may not show similar improvements. The urgent need of the hour is to implement comprehensive policies focused on tobacco control, indoor and outdoor pollution control, lung cancer screening and early detection, and improving access to treatment. Implementation of a national cancer control program is paramount. Critical steps include developing more robust cancer registries, training additional oncologists and onco-surgeons, expanding tertiary care facilities, and increasing clinical trial participation. More solution-oriented approaches such as trials addressing LMIC solutions (incorporating lower-cost options with improved efficacy outcomes) for LMIC problems are the way forward.[23,24] The government of Nepal is working toward providing better cancer care. Strict tobacco control policies have been implemented, and financial assistance of approximately 135,000 Nepalese Rupees is provided to families affected by a cancer diagnosis. Additionally, pilot public health insurance schemes have been initiated in select districts to improve healthcare accessibility in the country.[11] As the saying goes, “a journey of a thousand miles begins with a single step,” and Nepal is stepping forward slowly but surely toward a better future. With sustained efforts and a focus on accelerated progress, the country can move closer to achieving its goals.