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.

Improvement in radiation techniques for locally advanced cervical cancer during the last two decades

“…In the real world, penetration of techniques and an indication of possibilities of new modalities for radiation techniques will be necessary to monitor and survey the technical advantages 15. To successfully perform global clinical trials of cervical cancer, including concurrent chemoradiotherapy plus brachytherapy and immuno-oncology, novel standardization of radiotherapy will be resolutely required in the future 16…”

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

“…Cervical cancer is the fourth most common cancer and the most common gynecological malignancy ( 139 ), of which squamous cell carcinoma (SCC) is the most common type, accounting for approximately 80% of all cervical cancers ( 140 ). Treatment of advanced cervical cancer includes surgery, chemotherapy, and radiation therapy, but cervical cancer mortality remains high ( 141 ), mainly related to CSCs ( 142 ). Studies have suggested that ALDH1 can be used as a cervical CSC marker ( 143 , 144 ), which can lead to resistance to chemotherapy and is closely related to a poor prognosis ( 145 ).…”

Cost analysis of three-dimensional radiation therapy versus intensitymodulated chemoradiotherapy for locally advanced cervical cancer in Peruvian citizens

“…It has an incidence-mortality rate of 14.9–7.6 and 22.5–11.5 per 100,000 people on a Latin American and national level, respectively [ 1 ], thus making it one of the most costly oncologic pathologies for the health system. Compared with countries with a high level of resources, like the United States or Western European countries, developing countries like Peru and Indonesia, which have limited monetary and educational resources in healthcare, have the highest CC incidence and mortality rates [ 2 ]. CC is the fourth most common type of cancer in women under 45 [ 3 ], yet the average at diagnosis with CC is 51 [ 2 ].…”

“…Compared with countries with a high level of resources, like the United States or Western European countries, developing countries like Peru and Indonesia, which have limited monetary and educational resources in healthcare, have the highest CC incidence and mortality rates [ 2 ]. CC is the fourth most common type of cancer in women under 45 [ 3 ], yet the average at diagnosis with CC is 51 [ 2 ].…”