Patient Experience and Quality of Life During the Surveillance Phase of Uveal Melanoma: A Prospective Multi-method Study

Context and scientific background Uveal melanoma (UM) is the most common malignant ocular tumour in adults. It is a rare disease with an incidence of four to seven new cases per million per year in western countries (Mathis, 2018). The diagnosis of uveal melanoma is usually made when vision problems appear and the disease is still at a localized stage (in 95% of cases). Historically, the standard treatment for uveal melanoma was enucleation. Today, around 75% of patients can benefit from conservative treatment approaches such as brachytherapy or proton beam therapy without increasing the risk of metastasis or affecting survival. The visual prognosis of uveal melanoma depends on the localization of the tumour and efficacy of the treatment. Vital prognosis depends on the metastatic risk, which is related to the tumours' size and genomic characteristics (AJCC 7th Edition, 2015).

Up to 50% of patients develop metastases within a median time range of 2 to 3 years (Tuomaala & Kivelä, 2004). Metastatic progression develops most frequently in the liver (in >80% of cases). Once the disease spreads to the liver, median survival ranges from 3 to 12 months (Mariani, 2012) and response to treatment is rare. Estimating metastatic risk allows to provide personalized surveillance. For high risk patients, current international recommendations (NICE 2015) advise surveillance with liver CT or MRI (magnetic resonance imaging) every 6 months for over 10 years. If uveal melanoma metastases are diagnosed early, surgical liver resection can be considered in 25% of patients (Mariani, 2016). For the remaining 75%, systemic palliative care is recommended.

Various studies have addressed the effects of localized uveal melanoma and its treatment on quality of life (QoL). The QoL of patients with uveal melanoma appears to be significantly lower compared to matched general population (Erim, 2016; Miniati, 2018). Within the two years after treatment, overall QoL appears to be similar in patients treated by either enucleation or radiotherapy (Hope-Stone, 2016). Furthermore, no difference has been found between these treatments regarding specific aspects of QoL such as the ability to drive, ocular irritation, headaches, concerns regarding body image, and fear of recurrence (Hope-Stone, 2019). However, 6 months after treatment, functional difficulties are more important in enucleated patients, whereas difficulties in central and peripheral vision as well as in reading are higher in patients treated by radiotherapy (Hope-Stone, 2019). A large prospective study, conducted over a 20 year-period, concluded that overall quality of life was worse in enucleated patients than in patients treated with radiotherapy. However, this difference is not attributed to the treatment but to factors predisposing to treatment choices such as a more severe disease (e.g., larger tumour) (Damato, 2018).

During post-treatment surveillance, important aspects of QoL appear to be altered in patients treated for uveal melanoma. Depression and QoL levels seem to be worse around three months post-treatment (Amaro, 2010). Specific problems affecting QoL persist such such as body image troubles, especially in enucleated patients, as well as psychological adjustment, and social functioning difficulties, especially when vision problems persist.

As reported by items of the EORTC QLQ-C30 questionnaire, 39% of patients may have significant vision problems and 33% may report being 'worried about their future health' (Frenkel, 2018). The latter issue refers to fear of cancer recurrence (FCR) which is defined as the "fear, worry, or concern relating to the possibility that cancer will come back or progress" (Lebel, 2016). It is characterized by intense worry, intrusive thoughts and difficulty planning the future. Fear of recurrence (Suchocka-Capuano, 2011; Damato, 2018) has shown to be high and persists over time. These fears are related to uncertainty regarding future health. They result in anxiety and depressive symptoms, which significantly affect overall quality (Hope-Stone, 2015). Risk factors predisposing to distress include tumour stage and time since the beginning of surveillance. (Klingenstein, 2020) and persistent or emerging post-treatment symptoms and functional limitations (Brown, 2021). To our knowledge, only one study has examined unmet needs in patients with non-metastatic uveal melanoma, highlighting significant unmet medical information and psychological needs within 1 week after diagnosis and 3 months later (Williamson, 2018).