The 2019 coronavirus disease (COVID-19) pandemic has had a profound influence on different sectors of society, including health. This study hypothesized a significant impact of the pandemic on the quality of life and psychosocial well-being of urothelial cancer patients, specifically anticipating a decrease in anxiety and depression scores as the pandemic progressed. The primary objectives were to assess longitudinal changes in quality of life indexes, evaluate Healthcare Anxiety and Depression Scale (HADS) score trends over three years (2020-2022), and identify any correlational patterns between the progression of the pandemic and anxiety, depression, and stress levels among this cohort. A cross-sectional analysis was conducted on Eastern Cooperative Oncology Group (ECOG) 1 and Tumor Node Metastasis (TNM) stage 1 bladder cancer patients from the Timis County Emergency Clinical Hospital in Romania. Sixty patients were evaluated each year from 2020 to 2022, utilizing a detailed selection process involving the review of both the hospital database and paper records. Key data included demographic information, medical history, and responses to the Patient Health Questionnaire (PHQ-9), Short Form (SF-36), HADS, and Generalized Anxiety Disorder (GAD-7) questionnaires. A total of 163 completed questionnaires were analyzed, providing insight into various aspects of patients' experiences during the pandemic. Notably, the mean hospitalization days ranged from 3.6 ± 2.1 days in 2020 to 4.0 ± 2.4 days in 2022 ( = 0.663). Concerns that current symptoms might be pandemic-related spiked to 63.5% in 2021, but reduced to 50.9% in 2022, with this fluctuation being significant ( = 0.026). The perception of decreased quality of or accessibility to medical care was significant over the years, with a decline to 52.7% in 2022 ( = 0.033). Quality of life assessments demonstrated an upward trend, from an average score of 55.9 ± 8.9 in 2020 to 59.3 ± 8.8 in 2022 ( = 0.049). Interestingly, anxiety levels, as indicated by the HADS survey, revealed a significant decline from a score of 7.8 in 2020 to 6.5 in 2022 ( = 0.008). On the other hand, GAD-7 scores displayed a downward trend over the years, potentially indicative of developed coping strategies ( = 0.034). This study provides a comprehensive insight into the fluctuating dynamics of psychosocial factors and quality of life among urothelial cancer patients during the pandemic years. It underscores a potential adaptive response, as evidenced by the decrease in anxiety levels and an upward trend in the quality of life scores over the period. These findings highlight the resilience and adaptability of this patient cohort amidst the challenges posed by the pandemic, potentially guiding future interventions and supports in similar health crises.