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D Najjari-Jamal et al. (May 2024). Disease and treatment-related effects on sexual dysfunction and quality of life in cervical cancer survivors. www.HPVWorld.com, 267

Introduction
The standard of care for locally advanced cervical cancer (LACC) comprises concomitant radio(chemo)therapy (RTCHT) followed by image-guided adaptive brachytherapy (IGABT), which have significantly improved local control and reduced treatment-related morbidity compared to historical controls.

With current treatment, the incidence of severe toxicity is limited, so it is important to detect milder symptoms that can impact quality-of-life (QoL). Therefore, common side effects such as asthenia, gastrointestinal, genitourinary and sexual symptoms should be considered. Among these, sexual dysfunction is one of the most common side effects after treatment, affecting up to a third of treated cervical cancer patients.¹

Objectively, there are many treatment-related side effects that can affect sexual health, including gynaecological, genitourinary and gastrointestinal symptoms. These encompasses the genitourinary syndrome of menopause (GSM), a collection of symptoms and signs associated with a decrease in sex steroids and; involving changes in the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra, and urinary bladder.²

The effects of RTCHT and IGABT on the reproductive organs, and therefore sexual dysfunction, depend on several factors, such as age, treatment volume, dose and fractionation, technique and duration of treatment.

In the last years there have been many efforts to minimize the treatment-related sexual dysfunction. As one of the most influential factors in vaginal toxicity, recent attention has focused on vaginal dosing. Furthermore, The EMBRACE Collaborative group analyzed the risk of vaginal stenosis in 1045 patients in the observational, prospective, multicentre EMBRACE-I study and found that higher doses at the Posterior-Inferior Border of Symphysis (PIBS), PIBS+2 and recto-vaginal points were significantly associated with an increased risk of G≥2 vaginal stenosis.

In addition to radiotherapy (RT) and IGABT, other complementary treatments, such as chemotherapy and hormone therapy produce different grading toxicities that enhance sexual dysfunction and worsens quality of life.

How should we report morbidity?
Morbidity research focuses on treatment-related symptoms. The main organs at risk are the bladder, rectum, sigmoid, bowel and vagina. Genitourinary, gastrointestinal and sexual symptoms should be assessed before, during and after cancer treatment, using validated scales.

It is imperative to report severity grades, including mild morbidity, using CTCAE scales.³ However, mild and/or persistent symptoms are mainly underestimated by these scales, and there is a lack of morbidity assessment and patient-focused information on the impact of QoL. Therefore, it is essential in our clinical practice to address women's sexual health needs and concerns, taking into account the psychological, biological and interpersonal factors that influence sexual dysfunction.⁵

Hence, it is strongly recommended that the individual perception of patients with gynaecological tumours, as assessed by Patient-Reported Outcome (PRO), be included in their routine follow-up.⁶

How can we prevent and treat sexual dysfunction after treatment?
The most common signs/symptoms found during follow-up were vaginal dryness, shortening, tightening and pain during intercourse (crude incidences of 38.4%, 36.4%, 34.2% and 33.5%, respectively).¹ These all play an important role in sexual function and are reflected in PRO questionnaires, affecting sexual enjoyment in almost half of the sexually active patients.

This highlights the importance of prevention of vaginal morbidity and sexual rehabilitation after treatment.¹

With advances in technology and the introduction of Intensity-modulated radiotherapy (IMRT) and IGABT, vaginal doses have been reduced and severe toxicites have been limited. The EMBRACE-I study showed that vaginal stenosis was associated with high vaginal doses. Furthermore, the interventional, prospective and multicentre EMBRACE-II study protocol introduced some initiatives to reduce doses to the mid and lower vagina and to limit doses to the aforementioned points in order to reduce vaginal toxicity and improve sexual function and QoL (Figure 1).



Regular vaginal hydration is strongly recommended to prevent vaginal dryness. Also is recommended water-based lubricants during intercourse, since they prevent trauma and therefore dyspareunia. In addition, vaginal rehabilitation with vaginal penetration (dilators and/or intercourse) is essential. Their regular use shortly after the end of treatment prevents vaginal stenosis and vaginal adhesions and reduces G≥2 vaginal toxicities.⁶ Local oestrogens have shown benefit for GSM management with a safe profile. However, there is lack of evidence with long-term follow-up. Finally, some efforts are being made to treat vaginal shortnening and tightening with no-invasive procedures, such as CO₂ laser therapy. Some prospective studies have shown an improvement in sexual health. Despite these encouraging results, the evidence is weak and the results of a randomized trial are awaited (Table 1).



Currently, the Gyneacologial Radiation Oncology working group (GINECOR), on behalf of the Spanish Society of Radiation Oncology (SEOR), is working on guidelines for the management of sexual dysfunction in gynaecological cancer survivors.

Other articles included in the HPW monograph Treatment for cervical cancer

P Petric, U Mahantshetty. Treatment for cervical cancer-Part I: introduction to chemoradiation and external beam radiotherapy treatment.

P Petric, U Mahantshetty. Treatment for cervical cancer-Part II: brachytherapy and imaging techniques.

P Petric, U Mahantshetty. Treatment for cervical cancer-Part III: clinical results and conclusions.