Prognostic Indicators for Treatment Outcome in Cervical Cancer: A Mini Review

Abstract

Abbreviations: RT, radiotherapy; CCRT, concomitant chemoradiotherapy; BT, brachytherapy; PET, positron emission tomography; SUV, standard uptake value; MTV, metabolic tumor volume; TGV, tumor glycolytic volume IntroductionOver 50years ago, the Papanicolaou (Pap) smear was introduced in the US which has resulted in significant declines in cervical cancer incidences and deaths. However, cervical cancer remains the third most prevalent cancer in females worldwide.1,2 At advanced stages of the disease, treatment with radiotherapy (RT) alone decreases 5year survival rates leading to the implementation of multiple randomized clinical studies.3 Advancements found that combining chemotherapy and RT resulted in increased progression-free and overall survival with improved local control.3-5 As a result, in 1999 the US National Cancer Institute announced concomitant chemotherapy and RT (CCRT) as the standard of care for cervical cancer. 4,6 Since the acceptance of CCRT, the most significant advancement in treatment of cervical cancer over the last 20years has been brachytherapy (BT), which further improved survival rates.5 Dose and fractionation determination have been improved due to greater understanding of tumor biology and radiation effects, but remain limited by tolerance of normal tissue for late effects and therefore also limiting the cure rate.3,5 While CCRT involving BT advanced treatment outcomes, the improved survival rates have come at the cost of increased acute and late toxicity rates. 4,6 The current standard of care for locally advanced cervical cancer is a combination of external beam radiotherapy and intracavitary BT with concurrent chemotherapy. High dose rate BT is an important component in the curative management of cervix carcinoma and is most commonly delivered in five fractions using tandem&ring or tandem&ovoids applicators.7 Despite advanced treatment plans, treatment-related toxicity and recurrence still occur in a significant number of patients after treatment due to chemotherapy agents increasing radiosensitivity and ultimately the radiation hazard. 8,9 Although local control and toxicity rates have been slightly improving, recurrence rates remain as high as one-third, and toxicity rates remain as high as one-half among cervical cancer patients.10,11 Therefore, it has been of great clinical importance to investigate early indicators for optimal therapeutic response based on which treatments can be adjusted to minimize recurrence or toxicity outcomes. Once prognostic factors are identified, the aggressiveness of treatment can be properly determined. The current mini-review provides a summary of toxicity and recurrence outcomes, in addition to both clinical and biological indicators for improved treatment outcomes of cervical cancer patients. DiscussionRandomized studies of locally advanced cervical cancer patients showed CCRT improves long-term survival when compared to RT alone, though concurrent treatments result in more frequent acute toxicity and a 5% chance of late stage pelvic complications...