Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease that contributes substantially to cancer-related morbidity and mortality worldwide. In Turkey, it ranks as the fourth most common cancer in men, underscoring its national burden. Over the past decade, the treatment landscape has been reshaped by immune checkpoint inhibitors, antibody-drug conjugates, and targeted therapies, which have improved survival in both perioperative and metastatic settings.
Yet, despite these advances, patients in Turkey continue to face significant barriers-including limited reimbursement, high treatment costs, and infrastructure gaps-that hinder equitable access to life-prolonging therapies. This review explores the evolving therapeutic evidence and highlights the real-world challenges of implementing modern care in Turkey.
Title: Muscle-Invasive Bladder Cancer: Evolving Therapies and Real-World Access Gaps in Turkey
Authors: Muharrem Coşkunpınar, Evren Süer, Yüksel Ürün
Published in OncoDaily Medical Journal, September 2025.
Background
Bladder cancer remains a significant global health challenge, with an estimated 614,000 new cases and 220,000 deaths reported in 2022. Urothelial carcinoma is the predominant histological subtype, and muscle-invasive bladder cancer (MIBC) represents a particularly aggressive form associated with poor prognosis. In Turkey, bladder cancer is the fourth most common cancer in men, reflecting a notable disease burden.
Over the past decade, treatment has shifted dramatically with the introduction of immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and targeted therapies such as FGFR inhibitors. These advances have redefined the therapeutic paradigm for both perioperative and metastatic disease. However, real-world access to novel therapies remains uneven, with substantial financial and regulatory barriers in low- and middle-income countries (LMICs), including Turkey.
Bladder cancer
Bladder cancer is one of the most common cancers worldwide, developing in the urothelial cells that line the bladder. It is more frequent in men, with a threefold higher risk compared to women, and its incidence rises with age. In the United States, about 83,000 new cases and 17,000 deaths occur each year. The disease is strongly linked to smoking, chemical exposure, and chronic bladder irritation. Early symptoms, such as blood in the urine, are often subtle and overlooked, leading to delayed diagnosis. Survival outcomes vary widely by stage, ranging from a 77% five-year survival rate for localized disease to only 6% in metastatic cases.
Diagnosis and Management of Bladder Cancer
Bladder cancer diagnosis begins with cystoscopy, the gold standard, often followed by transurethral resection of bladder tumor (TURBT) under anesthesia for histological confirmation. Imaging – such as abdominopelvic CT or MRI – is critical for staging, with multiparametric MRI offering superior accuracy in assessing bladder wall invasion and treatment response. Chest CT is recommended to evaluate pulmonary spread, while bone scans, brain MRI, and PET-CT are reserved for high-risk or symptomatic patients. Management requires a multidisciplinary approach.
TURBT plays a central role in diagnosis, staging, and resection, though repeat TURBT may be needed in select non-muscle-invasive cases. For muscle-invasive bladder cancer (MIBC), radical cystectomy with pelvic lymph node dissection remains the gold standard, while partial cystectomy is reserved for carefully selected patients. Trimodality therapy – TURBT followed by chemoradiotherapy – offers a bladder-preserving alternative, particularly for those unfit for surgery, though 10–15% will ultimately require salvage cystectomy. Selected patients may also benefit from adjuvant radiotherapy to reduce local relapse risk. Across all strategies, close surveillance and multidisciplinary coordination are essential to optimize outcomes.
Methods and Study Design
This review was designed as a narrative landscape assessment. A non-systematic search of PubMed and Google Scholar identified English-language publications between 2015 and 2025. Clinical trials, guidelines, and policy documents on perioperative and metastatic MIBC management were analyzed. To contextualize real-world practice in Turkey, national drug approval and reimbursement data from the Turkish Medicines and Medical Devices Agency (TMMDA) were integrated, along with cost estimates and early access initiatives.
Current Evidence and Access Challenges
Over the past two decades, perioperative cisplatin-based chemotherapy, immune checkpoint inhibitors, antibody–drug conjugates, and FGFR-targeted therapies have transformed the care of muscle-invasive and metastatic bladder cancer. BA06 30894 and SWOG 8710 confirmed the survival benefit of neoadjuvant cisplatin-based regimens (HR 0.84 and 0.75). In the adjuvant setting, CheckMate 274 doubled DFS with nivolumab (20.8 vs 10.8 months; HR 0.70), while AMBASSADOR showed prolonged DFS with pembrolizumab (29.6 vs 14.2 months; HR 0.73).
NIAGARA demonstrated improved 24-month OS (82.2% vs 75.2%) with perioperative durvalumab plus chemotherapy. In metastatic disease, EV-302 established enfortumab vedotin plus pembrolizumab as a new standard (OS 31.5 vs 16.1 months). JAVELIN Bladder 100 validated maintenance avelumab (one-year OS 71.3% vs 58.4%), while THOR (erdafitinib) and DESTINY-PanTumor02 (trastuzumab deruxtecan) highlighted progress in biomarker-driven therapy.
Bladder Cancer in Turkey
Although therapeutic advances have reshaped the global standard of care for muscle-invasive and metastatic bladder cancer, their benefits are not equally realized across all regions. In many low- and middle-income countries (LMICs), including Turkey, patients face persistent obstacles that limit access to life-prolonging treatments. The main challenges in Turkey are:
- Regulatory and reimbursement delays: Of the major novel therapies approved by FDA and EMA, only avelumab maintenance is reimbursed in Turkey.
- High treatment costs: Annual costs of innovative regimens exceed the GDP per capita several-fold. For example, durvalumab perioperatively (~$66,000 annually) or erdafitinib (~$171,800 annually) are unaffordable in a country where the monthly minimum wage is ~$550.
- Infrastructure gaps: Molecular testing for FGFR alterations, HER2 expression, or ctDNA is not uniformly available, limiting precision oncology adoption.
- Socioeconomic inequities: Survival differences are evident by income level, with patients in the lowest quartile experiencing shorter median overall survival (55.9 vs 68.2 months) due to reduced receipt of neoadjuvant chemotherapy and inadequate lymph node dissection.
- Restricted second-line options: Most patients receive conventional cytotoxic regimens, as later-line immunotherapies or targeted agents remain unavailable.
The review also acknowledges limitations: lack of systematic methodology, absence of national registry data, and incomplete quantification of real-world therapy uptake. Thus, while evidence supports the efficacy of novel agents, the translation into routine care remains inconsistent in Turkey.
Insights and Implications
- Therapeutic efficacy is clear: Novel immunotherapies, ADCs, and targeted drugs achieve significant survival benefits in controlled trials.
- Access disparities drive outcomes: In Turkey, the combination of regulatory delays, high drug prices, and restricted reimbursement excludes most patients from benefiting.
- Economic context matters: When annual treatment costs are up to 11 times higher than GDP per capita, even middle-income patients are left with limited options.
- Precision oncology remains underdeveloped: Without broad access to biomarker testing, targeted agents such as erdafitinib and trastuzumab deruxtecan cannot be fully implemented.
- Need for systemic reform: Alignment with EMA guidance, expanded state reimbursement, and clinical trial participation are key strategies to reduce inequities.
Conclusion
Improving access to innovative therapies remains a critical priority for Turkey and other countries facing similar healthcare challenges. Expanding reimbursement coverage and adopting cost-effective strategies can help reduce disparities, ensure equitable care, and bring national practice closer to global oncology standards. While this review highlights key therapeutic advances and access barriers, it is limited by its narrative design and the absence of comprehensive national data, particularly regarding real-world treatment uptake in Turkey. These constraints should be acknowledged when interpreting the findings, but the overall message is clear: systemic reforms are urgently needed to translate clinical progress into meaningful survival gains for patients.
Read the full article here.