Global challenges of radiotherapy for the treatment of locally advanced cervical cancer

Abstract

Cervical cancer represents a significant portion of the global cancer burden for women, with low- and middle-income countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a triple-intervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiotherapy that must be addressed. We discuss and review evidence of the lack of adherence to guideline-recommended treatment, brachytherapy underutilization, limited access to radiotherapy in low- and middle-income countries, as well as regional limitations within high-income countries, as the major barriers to radiotherapy treatment for locally advanced cervical cancer. We further review ways these barriers are currently being addressed and, in some cases, make additional recommendations to address these issues. Finally, despite receiving recommended treatments, many patients with locally advanced cervical cancer have a poor prognosis. With effective administration of current standards of care, the global community will be able to shift focus to advancing treatment efficacy for these patients. We review several types of therapies under clinical investigation that are additions to concurrent chemoradiotherapy, including immune checkpoint inhibitors, antiangiogenic agents, DNA repair inhibitors, human papillomavirus vaccines, and radiosensitizing nanoparticles.

Keywords: cervical cancer; radiation oncology.

Figure 1

Relation of human development index to cervical cancer incidence and mortality. Reproduced with permission from Arbyn et al, Figures 1 and 2 and Supplemental Figure 1. Countries with a lower human development index also tend toward higher cervical cancer incidence and mortality rates. Incidence and mortality were estimated for 2018. The original sources for the human development index were United Nations Development Programme, New York, 2016 and International Agency for Research on Cancer, Lyon, 2018.

Figure 2

Challenges and solutions to achieving effective radiotherapy for locally advanced cervical cancer. The inner circle represents the goal, the outer ring shows barriers to the goal, and the outside text are actions/ideas needed to overcome barriers.

Figure 3

Distribution of megavoltage (A) and brachytherapy (B) equipment per the International Atomic Energy Agency Directory of Radiotherapy Centres (DIRAC) as of February 2021. Data are voluntarily submitted to DIRAC by several sources including individuals working in a radiotherapy center, national DIRAC coordinators, the International Atomic Energy Agency/World Health Organization mailed dosimetry audit program, third-party organizations, and other sources. The International Atomic Energy Agency DIRAC website (https://dirac.iaea.org/) was accessed on March 28, 2021. Distribution of megavoltage and brachytherapy units across the globe were generated by the website and were current as of February 28, 2021.