Calendar time trends in synchronous metastatic urinary bladder cancer before and after the introduction of immune checkpoint inhibitors: A nation-wide population-based cohort study

Karin Söderkvist^1*Christel Häggström^1,2Oskar Hagberg³Firas Aljabery⁴Truls Gårdmark⁵Lars Holmberg²Abolfazl Hosseini⁵Tomas Jerlström⁶Henrik Kjölhede⁷Per-Uno Malmström²Amir Sherif¹Fredrik Liedberg³Anders Ullén⁵

• ¹Umeå University, Umeå, Sweden
• ²Uppsala Universitet, Uppsala, Sweden
• ³Lunds Universitet, Lund, Sweden
• ⁴Linkopings universitet, Linköping, Sweden
• ⁵Karolinska Institutet, Stockholm, Sweden
• ⁶Orebro universitet, Örebro, Sweden
• ⁷Sahlgrenska universitetssjukhuset, Gothenburg, Sweden

Introduction For the 3-5 % of patients diagnosed with urinary bladder cancer presenting with distant metastases, the five-year survival probability remains below 10% (1-3). Since the late 1980s, platinum-based combination chemotherapy has been the cornerstone of treatment for metastatic urinary bladder cancer (mUBC) (4, 5). For cisplatin-ineligible patients, carboplatin-gemcitabine was established as an alternative in 2011 (6, 7), and is currently used as first-line chemotherapy in approximately half of the patients treated systemically for mUBC (8). However, platinum-based regimens are associated with a high incidence of serious adverse events (5, 7). Consequently, a substantial proportion of patients with mUBC do not receive any systemic chemotherapy (9). Vinflunine was approved in Europe in 2009 as second-line chemotherapy, though with limited clinical benefit (10, 11). A new era in the systemic treatment of mUBC was marked by the approval of immune checkpoint inhibitors (ICI) 2017 (12, 13). ICIs demonstrated not only an improved overall survival but also a more favorable toxicity profile. Recent population-based studies have reported improved survival among systemically treated patients with mUBC following the introduction of ICI (14). Given the historically low uptake of systemic therapy in the real-world setting of mUBC, it remains unclear whether the introduction of immune checkpoint inhibitors (ICI) has translated into improved survival at the population level. As the treatment landscape for mUBC continues to evolve rapidly, benchmarking treatment patterns and survival outcomes in real-world populations is essential to guide clinical practice and policy. We used the Bladder Cancer Data Base Sweden (BladderBase) 2.0 (15) to investigate survival trends among patients diagnosed with synchronous mUBC between 1997 and 2019 across calendar periods defined by the introduction of novel systemic therapies. We hypothesized that survival in the overall mUBC population improved after the introduction of ICI (2017-2019), due to both the availably of a novel treatment option and an increased proportion of patients eligible for systemic treatment due to ICIs favorable toxicity profile.