Abstract
Introduction
Urothelial carcinomas (UC) are the fourth most common tumours. Approximately, 50% of patients with invasive bladder cancer relapse after radical cistectomy (RC). In this report, we present the case of peritoneal carcinomatosis from bladder UC treated with cytoreductive surgery plus the administration of hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).
Case Presentation
A 34-year-old woman diagnosed with high-grade bladder cancer with peritoneal recurrence in 2017. She underwent cytoreductive surgery followed by HIPEC with mitomycin C. Histopathological results showed metastases from UC in the left ovary and right diaphragmatic peritoneum. In 2021, the patient underwent surgery after treatment with atezolizumab for abdominal wall recurrence. Today, the patient is alive and free of tumor recurrence 12 months after the last surgery.
Discussion
Despite advances in surgical technique and patient selection, the risk of relapse remains high among patients with muscle-invasive bladder cancer. We face the case of a young female patient with local, peritoneal, and lymphatic recurrence of bladder cancer after RC who had a partial response to chemotherapy. The possibility of CRS + HIPEC is offered by the surgical oncology unit, referent in the management of peritoneal carcinomatosis. Surgery is capable of resecting residual tumor in patients with a partial response or who have been erroneously underdiagnosed.
Conclusion
CRS + HIPEC might be a valid option to be considered in well-selected patients and to be performed in reference units. There is a need for more collaborative clinical trials and prospective studies addressing the role of surgery in patients with metastatic bladder cancer.
Keywords: Peritoneal carcinomatosis, Urothelial carcinoma, Bladder cancer, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy
Introduction
Urothelial carcinomas (UC) are the fourth most common tumors. They are located in the lower (bladder and urethra) or the upper urinary tract. Bladder tumors account for 90–95% of urothelial carcinomas and are the most common urinary tract malignancy. Approximately, 25% of patients will present with muscle-invasive bladder cancer (MIBC) or metastatic disease [1, 2].
Approximately, 50% of patients with MIBC relapse after radical cistectomy (RC) [2]. Pelvic recurrences carry a poor prognosis despite treatment with a median survival of 4 to 8 months. The multidisciplinary treatment of these recurrences includes chemotherapy, radiotherapy, and surgery [3]. Standard first-line treatment for suitable patients with a good renal function is cisplatin-based combination chemotherapy [4].
In this report, we present the case of peritoneal carcinomatosis from bladder UC treated with cytoreductive surgery plus administration of hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).
Case Presentation
The patient was a 34-year-old woman with clinical history of nodular sclerosis Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, dacarbazine, and supradiaphragmatic radiotherapy in 2006 with complete remission. In July 2013, she underwent limited surgery for high-grade bladder cancer, developing a complicated vesico-vaginal fistula. In September 2014, she was diagnosed with urethral recurrence of UC and consequently underwent RC with hysterectomy, urethrectomy, and construction of Bricker bladder. Histopathological findings showed pT2 stage [5], with infiltration of the left parametrium. In April 2016, there was evidence of recurrence with peritoneal implants and right obturator lymphadenopathies. The patient therefore received 6 cycles of cisplatin and gemcitabine. After a partial response (Fig. 1), the case was discussed in the multidisciplinary committee, proposing CRS + HIPEC.
Fig. 1.
Partial response of peritoneal implants and right obturator lymphadenopaties after 6 cycles of cisplatin and gemcitabine
In February 2017, she underwent total pelvic peritonectomy, bilateral salpingo-oophorectomy, vaginal vault resection, right diaphragmatic peritonectomy, and omentectomy. HIPEC with mitomycin C at 42ºC was administered for 60 min in an open technique. There was no postoperative morbidity. Histopathological results showed metastases from UC in the left ovary and right diaphragmatic peritoneum. No lymphatic metastases were found.
In August 2018, the local recurrence was found at the abdominal wall in the right iliac fossa and possible right iliac lymph node involvement. The patient then received 26 cycles of atezolizumab until January 2021, with stable disease in follow-up. The biopsy of the abdominal lesion was positive for malignancy, so in March 2021, the patient underwent surgery with resection of the abdominal lesion and right iliac lymphadenectomy. Today, the patient is alive and free of tumor recurrence 12 months after the last surgery.
Discussion
We have reported a case of MIBC recurring with peritoneal carcinomatosis that was treated with CRS + HIPEC. The patient did not present significant risk factors for the development of urothelial carcinoma of the bladder [6]. Despite advances in surgical technique and patient selection, the risk of relapse remains high with reported 5-year disease-free survival of approximately 50% among patients with MIBC. It has been described that in patients with local or distance recurrence after RC, post-recurrence chemotherapy and metastasectomy was found to be independent predictor of better post-recurrence overall survival [7].
We face the case of a young female patient with local, peritoneal, and lymphatic recurrence of bladder cancer after RC who had a partial response to chemotherapy. The possibility of CRS + HIPEC is offered by the surgical oncology unit, referent in the management of peritoneal carcinomatosis [8, 9]. Although cytoreduction in these cases has been described [10, 11], the use of HIPEC in this context has not been proved previously. The efficacy of mitomycin C in the treatment of bladder cancer has been demonstrated in multiple studies and meta-analyses [12].
The main reason to justify CRS is that even though urothelial carcinoma is a chemosensitive tumor, cure is rarely achieved with the chemotherapy protocols currently available [13]. Besides, surgery is capable of resecting residual tumor in patients with a partial response or who have been erroneously underdiagnosed [14–16]. Although the aforementioned justifications give a strong argument in favor of agressive local treatment as cytoreductive surgery and HIPEC, more evidence would be needed to recommend it.
Conclusion
Locally advanced or metastatic bladder cancer remains a lethal disease with little improvement in outcomes since the introduction of systemic cisplatin-based chemotherapy. Evidence suggests a role for surgery and/or other consolidation therapies in the management of this subgroup of patients. CRS + HIPEC might be a valid option to be considered in well-selected patients and to be performed in reference units. There is a need for more collaborative clinical trials and prospective studies addressing the role of surgery in patients with metastatic bladder cancer.
Author Contributions
Study design: Blanca Rufián Andújar and Francisca Valenzuela-Molina. Manuscript writing: Blanca Rufián Andújar and Álvaro Arjona-Sánchez. Data acquisition (surgeons): Lidia Rodríguez-Ortiz and Álvaro Arjona-Sánchez. Critical revision: Álvaro Arjona Sánchez and Sebastián Rufián Peña; Francisco Javier Briceño Delgado. The authors read and approved the final manuscript.
Declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Patient Consent
The patient provided signed consent for the surgery alongside with accepting that her case may be used for educational and scientific purposes.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Rouprêt M, Babjuk M, Compérat E, Zigeuner R, Sylvester RJ, Burger M, Cowan NC, Gontero P, Van Rhijn BWG, Mostafid AH, Palou J, Shariat SF. European Association of Urology Guidelines on upper urinary tract urothelial carcinoma: 2017 update. Eur Urol. 2018;73(1):111–122. doi: 10.1016/j.eururo.2017.07.036. [DOI] [PubMed] [Google Scholar]
- 2.Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, Hernández V, Linares Espinós E, Lorch A, Neuzillet Y, Rouanne M, Thalmann GN, Veskimäe E, Ribal MJ, van der Heijden AG. European Association of Urology Guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol. 2021;79(1):82–104. doi: 10.1016/j.eururo.2020.03.055. [DOI] [PubMed] [Google Scholar]
- 3.Soukup V, Babjuk M, Bellmunt J, Dalbagni G, Giannarini G, Hakenberg OW, Herr H, Lechevallier E, Ribal MJ. Follow-up after surgical treatment of bladder cancer: a critical analysis of the literature. Eur Urol. 2012;62(2):290–302. doi: 10.1016/j.eururo.2012.05.008. [DOI] [PubMed] [Google Scholar]
- 4.Bellmunt J, Petrylak DP. New therapeutic challenges in advanced bladder cancer. Semin Oncol. 2012;39(5):598–607. doi: 10.1053/j.seminoncol.2012.08.007. [DOI] [PubMed] [Google Scholar]
- 5.Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474 [DOI] [PubMed]
- 6.Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, Kiemeney L, Lotan Y, Pang K, Silverman DT, Znaor A, Catto JWF. Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018. Eur Urol. 2018;74(6):784–795. doi: 10.1016/j.eururo.2018.09.001. [DOI] [PubMed] [Google Scholar]
- 7.Nakagawa T, Hara T, Kawahara T, Ogata Y, Nakanishi H, Komiyama M, Arai E, Kanai Y, Fujimoto H. Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy. J Urol. 2013;189(4):1275–1281. doi: 10.1016/j.juro.2012.10.065. [DOI] [PubMed] [Google Scholar]
- 8.Arjona-Sánchez A, Medina-Fernández FJ, Muñoz-Casares FC, Casado-Adam A, Sánchez-Hidalgo JM, Rufián-Peña S. Peritoneal metastases of colorectal origin treated by cytoreduction and HIPEC: an overview. World J Gastrointest Oncol. 2014;6(10):407–412. doi: 10.4251/wjgo.v6.i10.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Muñoz-Casares FC, Medina-Fernández FJ, Arjona-Sánchez Á, Casado-Adam Á, Sánchez-Hidalgo JM, Rubio MJ, Ortega-Salas R, Muñoz-Villanueva MC, Rufián-Peña S, Briceño FJ. Peritonectomy procedures and HIPEC in the treatment of peritoneal carcinomatosis from ovarian cancer: long-term outcomes and perspectives from a high-volume center. Eur J Surg Oncol. 2016;42(2):224–233. doi: 10.1016/j.ejso.2015.11.006. [DOI] [PubMed] [Google Scholar]
- 10.Galsky MD, Domingo-Domenech J, Sfakianos JP, Ferket BS. Definitive management of primary bladder tumors in the context of metastatic disease: who, how, when, and why? J Clin Oncol. 2016;34(29):3495–3498. doi: 10.1200/JCO.2016.68.3714. [DOI] [PubMed] [Google Scholar]
- 11.Seisen T, Sun M, Leow JJ, Preston MA, Cole AP, Gelpi-Hammerschmidt F, Hanna N, Meyer CP, Kibel AS, Lipsitz SR, Nguyen PL, Bellmunt J, Choueiri TK, Trinh QD. Efficacy of high-intensity local treatment for metastatic urothelial carcinoma of the bladder: a propensity score-weighted analysis from the national cancer data base. J Clin Oncol. 2016;34(29):3529–3536. doi: 10.1200/JCO.2016.66.7352. [DOI] [PubMed] [Google Scholar]
- 12.Shelley MD, Mason MD, Kynaston H. Intravesical therapy for superficial bladder cancer: a systematic review of randomised trials and meta-analyses. Cancer Treat Rev. 2010;36(3):195–205. doi: 10.1016/j.ctrv.2009.12.005. [DOI] [PubMed] [Google Scholar]
- 13.von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–4608. doi: 10.1200/JCO.2005.07.757. [DOI] [PubMed] [Google Scholar]
- 14.Meijer RP, Mertens LS, van Rhijn BW, Bex A, van der Poel HG, Meinhardt W, Kerst JM, Bergman AM, Fioole-Bruining A, van Werkhoven E, Horenblas S. Induction chemotherapy followed by surgery in node positive bladder cancer. Urology. 2014;83(1):134–139. doi: 10.1016/j.urology.2013.08.082. [DOI] [PubMed] [Google Scholar]
- 15.Ho PL, Willis DL, Patil J, Xiao L, Williams SB, Melquist JJ, Tart K, Parikh S, Shah JB, Delacroix SE, Navai N, Siefker-Radtke A, Dinney CP, Pisters LL, Kamat AM. Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: the M.D. Anderson Cancer Center Experience. Urol Oncol. 2016;34(2):59.e1–8. doi: 10.1016/j.urolonc.2015.08.012. [DOI] [PubMed] [Google Scholar]
- 16.Abufaraj M, Dalbagni G, Daneshmand S, Horenblas S, Kamat AM, Kanzaki R, Zlotta AR, Shariat SF. The role of surgery in metastatic bladder cancer: a systematic review. Eur Urol. 2018;73(4):543–557. doi: 10.1016/j.eururo.2017.09.030. [DOI] [PMC free article] [PubMed] [Google Scholar]