Cancer Research and Treatment

Original Articles

Genitourinary cancer

Efficacy and Safety of Ifosfamide and Mesna in Metastatic Castration-Resistant Prostate Cancer after Taxane-Based Chemotherapy and Novel Hormonal Therapy Failure: Chang Gon Kim, Yeo Gyeong Ko, Jongjin Yoon, Chung Lee, Seung Hoon Beom, Young-Deuk Choi, Woong Kyu Han, Won Sik Ham, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daeseong Kim, Eun Sil Baek, Sangwoo Kim, Minsun Jung, Sang Joon Shin; Cancer Res Treat. 2026;58(2):603-612. Published online June 9, 2025; DOI: https://doi.org/10.4143/crt.2025.155

Abstract PDF Supplementary Material PubReader ePub: Purpose
Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).
Materials and Methods
Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m² and mesna 1,500 mg/m² on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA₅₀) or >90% (PSA₉₀), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed.
Results
A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS.
Conclusion
Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

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Real-World Efficacy of Intravesical Gemcitabine for BCG-Unresponsive Non–muscle-Invasive Bladder Cancer: Hye Won Lee, Eui Hyun Jung, Kyung Hwan Kim, Hong Koo Ha, Jong Jin Oh, Seok Ho Kang, Seung-hwan Jeong, Hyeong Dong Yuk, Ji Eun Heo, Won Sik Ham, Eu Chang Hwang, Seung Il Jung, Wan Song, Bumjin Lim, Bumsik Hong, Byung Chang Jeong, Ho Kyung Seo; Cancer Res Treat. 2026;58(2):591-602. Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.100

Abstract PDF PubReader ePub: Purpose
This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC).
Materials and Methods
This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models.
Results
Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course.
Conclusion
Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

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Genitourinary Cancer

Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma: Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho; Cancer Res Treat. 2021;53(4):1174-1183. Published online March 17, 2021; DOI: https://doi.org/10.4143/crt.2021.031

Abstract PDF Supplementary Material PubReader ePub

Purpose
Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs.
Materials and Methods
All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation.
Results
FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival.
Conclusion
FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

Citations

Citations to this article as recorded by

Protein iron transporters as potential therapeutic targets in cancer: A review
Ruchira Banerjee, Bintee Bintee, Mangala Hegde, Bandari BharathwajChetty, Mohammed S. Alqahtani, Mohamed Abbas, Athba Alqahtani, Gautam Sethi, Latha Rangan, Zhaowu Ma, Ajaikumar B. Kunnumakkara
International Journal of Biological Macromolecules.2025; 327: 146695. CrossRef
Differences in genomic profile of high-grade urothelial carcinoma according to tumor location
Cheol Keun Park, Nam Hoon Cho
Urologic Oncology: Seminars and Original Investigations.2022; 40(3): 109.e1. CrossRef
The Role of Iron in Cancer Progression
Qianqian Guo, Liwen Li, Shanshan Hou, Ziqiao Yuan, Chenhui Li, Wenzhou Zhang, Lufeng Zheng, Xiaoman Li
Frontiers in Oncology.2021;[Epub] CrossRef

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