The Long-Term Effects on Recurrence and Progression of Bladder Tumors of Chemotherapeutic Agents Used After Transurethral Resection
Öz
Objective: Early single dose chemotherapy may have a reducing effect on recurrence and progression. In this study, we aimed to compare non-muscle invasive patients diagnosed with bladder cancer who did not receive early single dose chemotherapy and those who received intravesical Epirubicin or Gemcitabine in terms of recurrence and progression.
Material and Methods: 116 patients were followed up for 48 months (May 2020-June 2022) with diagnosis of primary non-invasive bladder cancer. After transurethral resection of the bladder, patients were followed up with 3 groups: who received intravesical epirubicin, who received gemcitabine, who did not receive any chemotherapeutic agent.
Results: The mean age was 63. There were no statistically significant difference in age and, body mass index. Recurrence was determined 57.1% (n=20), 40% (n=18), and 41.7% (n=15) (p=0.263) of the patients, respectively who were not administered any intravesical agent, were administered Epirubicin and, Gemcitabine. While recurrence rates were observed 50%, 25%, 0% (p=0.177) respectively, in low-risk, no progression was detected. In intermediate risk group, 66.7%, 33.3%, 42.8% (p=0.378) recurrence, and 33.3%, 22.7%, 6.7% (p=0.282) progression were detected, respectively. High-risk group, recurrence was found in 56%, 64.2%, 56.2% (p=0.866) of the patients and progression 8%, 14.3%, 6.3% (p=0.723) respectively. In low-grade group, 35.7%, 42.9%, 21.4% (p=0.045) recurrence, and 16.6%, 12.1%, and 4.3% (p=0.164) progression were determined , respectively. In the high-grade group, 58.8%, 50%, 69.2% (p=0.982) recurrence, 5.9%, 16.6% and 7.7% (p=0.581) progression were detected, respectively.
Conclusion: These findings demonstrated that intravesical chemotherapeutics can delay or prevent recurrence and progression, should therefore be administered in early postoperative period. Gemcitabine is not in widespread use and has been found to be a good alternative.
Anahtar Kelimeler
Bladder cancer Recurrence Progression Epirubicin Gemcitabine
Etik Beyan
The study was authorized by the Ethics Committee at the Faculty of Medicine, Cumhuriyet University, on the date of 05/20/2020 With ethical number: 2020-05/02.
Destekleyen Kurum
No financial support was received.
Kaynakça
- 1. IARC, Cancer Today. Estimated number of new cases in 2020, worldwide, both sexes, all ages. 2021
- 2. Burger M, Catto JW, Dalbagni G. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234- 241. https://doi.org/10.1016/j.eururo.2012.07.033
- 3. Grossman, H. Barton et al. ‘Intravesical Therapy – BCG and Beyond’. 2019; Jan:73 – 80. https://doi.org/10.3233/ BLC-180198
- 4. Sylvester RJ, van der Meijden AP, Oosterlinck W. Predicting recurrence and progression in indİVidual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466-477.https://doi.org/10.1016/j.eururo.2005.12.031
- 5. Brocks CP, Büttner H, Böhle A. Inhibition of tumor implantation by intravesical gemcitabine in a murine model of superficial bladder cancer. The Journal of Urology. 2005;Sep;174(3):1115-1118. https://doi.org/10.1097/01. ju.0000168657.51551.49
- 6. Sylvester RJ, Rodríguez O, Hernández V, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. 2021;79(4):480-488. https:// doi.org/10.1016/j.eururo.2020.12.033
- 7. R. J. Cersosimo and W. K. Hong, “Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue,” Journal of Clinical Oncology. 1986. vol. 4, no. 3, pp. 425–439. https://doi.org/10.1200/ JCO.1986.4.3.425
- 8. S. V. Onrust, L. R. Wiseman, and K. L. Goa, “Epirubicin,” Drugs & Aging, 1999. vol. 15, no. 4, pp. 307–333 https://doi. org/10.2165/00002512-199915040-00006
- 9. Oosterlinck W, Kurth KH, Schröder F. A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol. 1993;149:749- 52. https://doi.org/10.1016/s0022-5347(17)36198-0
- 10. Masters JR, Popert RJ, Thompson PM. Intravesical chemotherapy with epurubicin: a dose response study. J Urol. 1999;161:1490-3.
- 11. Sylvester, R.J. Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. 2016;69: 231. https://doi.org/10.1016/j.eururo.2015.05.050
- 12. P. Huang, S. Chubb, L. W. Hertel, G. B. Grindey, and W. Plunkett, “Action of 2’,2’-difluorodeoxycytidine on DNA synthesis,” Cancer Research, 1991. vol. 51, no. 22, pp. 6110–6117.
- 13. Ye HB, Chen S, Wang J. A comparatİVe study of gemcitabine and epirubicin in adjuvant chemotherapy of non muscle invasive bladder cancer. Research Square; 2020. https://doi.org/10.21203/rs.3.rs-20323/v1
- 14. Messing, E.M. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-İnvasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. Jama. 2018; 319:1880. https://doi.org/10.1001/jama.2018.4657
- 15. Jianglei Zhang, Miao Li, Ze Chen, Jun OuYang, Zhixin Ling, “Efficacy of Bladder Intravezical Chemotherapy with Three Drugs for Preventing Non-Muscle-İnvasive Bladder Cancer Recurrence”, Journal of Healthcare Engineering; 2021 https://doi.org/10.1155/2021/2360717
Mesane Tümörlerinde Transüretral Rezeksiyondan Sonra Kullanılan Kemoterapötik Ajanların Nüks Ve Progresyon Üzerindeki Uzun Vadeli Etkileri
Öz
Amaç: Erken tek doz kemoterapinin nüks ve progresyonu azaltıcı etkisi olabilmektedir. Çalışmamızda mesane kanseri tanısı almış, erken tek doz kemoterapi almayan ve intravezikal Epirubisin veya Gemcitabin alan kasa invaziv olmayan hastaların nüks ve progresyon açısından karşılaştırılmasını amaçladık.
Gereç ve Yöntemler: Primer non-invaziv mesane kanseri tanısı almış 116 hasta 48 ay (mayıs 2020-haziran 2022) boyunca takip edildi. Mesanenin transüretral rezeksiyonundan sonra hastalar 3 grupta takip edildi: intravezikal epirubisin alanlar, gemcitabin alanlar ve herhangi bir kemoterapi ajanı almayanlar.
Bulgular: Olguların ortalama yaşı 63 idi. Hastalarda yaş ve vücut kitle indeksi arasında istatistiksel olarak fark yoktu. Herhangi bir intravezikal ajan uygulanmayan, Epirubisin, Gemcitabine uygulanan hastalarda sırasıyla %57,1 (n=20), %40 (n=18) ve %41,7 (n=15) (p=0,263) oranında nüks saptandı. Düşük riskli grupta nüks oranları sırasıyla %50, %25, %0 (p=0,177) olarak gözlenirken, progresyon saptanmadı. Orta riskli grupta ise sırasıyla %66,7, %33,3, %42,8 (p=0,378) nüks, %33,3, %22,7, %6,7 (p=0,282) oranında progresyon saptandı. Yüksek riskli grupta ise hastaların sırasıyla %56, %64,2, %56,2’sinde nüks (p=0,866), %8, %14,3, %6,3’ünde (p=0,723) progresyon saptandı. Düşük dereceli grupta sırasıyla %35,7, %42,9, %21,4 nüks (p=0,045) ve %16,6, %12,1 ve %4,3 (p=0,164) progresyon saptandı. Yüksek dereceli grupta sırasıyla %58,8, %50, %69,2 nüks (p=0,982), %5,9, %16,6 ve %7,7 (p=0,581) progresyon belirlendi.
Sonuç: Bu bulgular, intravezikal kemoterapötiklerin nüks ve progresyonu geciktirebileceğini ve/veya önleyebileceğini, bu nedenle erken postoperatif dönemde uygulanması gerektiğini göstermiştir. Gemsitabin yaygın kullanımda olmayıp alternatif olarak iyi bir tercih olduğu görülmüştür.
Anahtar Kelimeler
Kaynakça
- 1. IARC, Cancer Today. Estimated number of new cases in 2020, worldwide, both sexes, all ages. 2021
- 2. Burger M, Catto JW, Dalbagni G. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234- 241. https://doi.org/10.1016/j.eururo.2012.07.033
- 3. Grossman, H. Barton et al. ‘Intravesical Therapy – BCG and Beyond’. 2019; Jan:73 – 80. https://doi.org/10.3233/ BLC-180198
- 4. Sylvester RJ, van der Meijden AP, Oosterlinck W. Predicting recurrence and progression in indİVidual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466-477.https://doi.org/10.1016/j.eururo.2005.12.031
- 5. Brocks CP, Büttner H, Böhle A. Inhibition of tumor implantation by intravesical gemcitabine in a murine model of superficial bladder cancer. The Journal of Urology. 2005;Sep;174(3):1115-1118. https://doi.org/10.1097/01. ju.0000168657.51551.49
- 6. Sylvester RJ, Rodríguez O, Hernández V, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. 2021;79(4):480-488. https:// doi.org/10.1016/j.eururo.2020.12.033
- 7. R. J. Cersosimo and W. K. Hong, “Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue,” Journal of Clinical Oncology. 1986. vol. 4, no. 3, pp. 425–439. https://doi.org/10.1200/ JCO.1986.4.3.425
- 8. S. V. Onrust, L. R. Wiseman, and K. L. Goa, “Epirubicin,” Drugs & Aging, 1999. vol. 15, no. 4, pp. 307–333 https://doi. org/10.2165/00002512-199915040-00006
- 9. Oosterlinck W, Kurth KH, Schröder F. A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol. 1993;149:749- 52. https://doi.org/10.1016/s0022-5347(17)36198-0
- 10. Masters JR, Popert RJ, Thompson PM. Intravesical chemotherapy with epurubicin: a dose response study. J Urol. 1999;161:1490-3.
- 11. Sylvester, R.J. Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. 2016;69: 231. https://doi.org/10.1016/j.eururo.2015.05.050
- 12. P. Huang, S. Chubb, L. W. Hertel, G. B. Grindey, and W. Plunkett, “Action of 2’,2’-difluorodeoxycytidine on DNA synthesis,” Cancer Research, 1991. vol. 51, no. 22, pp. 6110–6117.
- 13. Ye HB, Chen S, Wang J. A comparatİVe study of gemcitabine and epirubicin in adjuvant chemotherapy of non muscle invasive bladder cancer. Research Square; 2020. https://doi.org/10.21203/rs.3.rs-20323/v1
- 14. Messing, E.M. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-İnvasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. Jama. 2018; 319:1880. https://doi.org/10.1001/jama.2018.4657
- 15. Jianglei Zhang, Miao Li, Ze Chen, Jun OuYang, Zhixin Ling, “Efficacy of Bladder Intravezical Chemotherapy with Three Drugs for Preventing Non-Muscle-İnvasive Bladder Cancer Recurrence”, Journal of Healthcare Engineering; 2021 https://doi.org/10.1155/2021/2360717
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Üroloji |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Mayıs 2025 |
| Gönderilme Tarihi | 12 Ocak 2025 |
| Kabul Tarihi | 24 Mayıs 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 17 Sayı: 2 |
