Predictors of pathologic response to neoadjuvant chemotherapy in muscle-invasive bladder cancer
DOI:
https://doi.org/10.52786/isu.a.50Keywords:
Muscle-invasive bladder cancer, neoadjuvant chemotherapy, pathologic response, predictors, carboplatinAbstract
Objective: To identify factors that could predict pathologic response to neoadjuvant (NAC) therapy in muscle invasive bladder cancer (MIBC) patients and report the impact of NAC on the risk of perioperative complications after radical cystectomy at our institution.
Materials and Methods: We reviewed the hospital database from January 2014 to March 2021 for MIBC patients who received NAC prior to radical cystectomy (RC). All patients were divided into a responder (pT ≤ T1) or non-responder group (> pT2). Data was analyzed to determine the factors associated with pathologic response to NAC. A subgroup analysis of the gemcitabine and carboplatin (GCb) regimens was also carried out.
Results: Out of the 50 patients who met the inclusion criteria, 13 (26%) were categorized as responders and 37 (74%) as non-responders. With regard to NAC variables, 12 patients (24%) received cisplatin-based NAC, and 38 patients (74%) received GCb. From the multivariate analysis, pretreatment hemoglobin (Hb) > 12 g/dl (OR 16.42, 95% CI 1.78-151.86, p = 0.01) and neutrophil-to-lymphocyte ratio (NLR) < 3 (OR 12.81, 95% CI 1.36-120.9, p = 0.03) were associated with significantly increased odds of pathologic response, while tumor size < 4 cm (OR 12, 95% CI 1.92-75.05, p = 0.008) was associated with significantly increased odds of pathologic response in the subgroup analysis.
Conclusions: Pretreatment Hb and NLR were independently associated with pathologic response to NAC. For MIBC patients who are cisplatin ineligible, GCb followed by RC may be the recommended treatment, particularly in those with tumors less than 4 cm in size. In addition, administering NAC prior to RC does not increase the risk of perioperative complications.
References
Prout GR, Marshall VF. The prognosis with untreated bladder tumors. Cancer 1956;9:551-8.
Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349:859-66.
Winquist E, Kirchner TS, Segal R, Chin J, Lukka H. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004;171:561-9.
Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48:202-5;discussion 5-6.
Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011;29:2171-7.
Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. J Urol 2017;198:552-9.
Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, et al. European Association of Urology Guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol 2021;79:82-104.
Network NCC. NCCN clinical practice guidelines in oncology: bladder cancer, version 4.2021. 2021.
Splinter TA, Scher HI, Denis L, Bukowski R, Simon S, Klimberg I, et al. The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer--Genitourinary Group. J Urol 1992;147:606-8.
Sonpavde G, Goldman BH, Speights VO, Lerner SP, Wood DP, Vogelzang NJ, et al. Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy. Cancer 2009;115:4104-9.
Rosenblatt R, Sherif A, Rintala E, Wahlqvist R, Ullén A, Nilsson S, et al. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy andradical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol 2012;61:1229-38.
Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Vavas- sori I, Barni S. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol 2014;65:350-7.
Waingankar N, Jia R, Marqueen KE, Audenet F, Sfakianos JP, Mehrazin R, et al. The impact of pathologic response to neoadjuvant chemotherapy on conditional survival among patients with muscle-invasive bladder cancer. Urol Oncol 2019;37:572.e21-8.
Pearce SM, Ashrafi A, Winter M, Ghodoussipour S, Zainfeld D, Gill I, et al. Predictors of pathologic response after radical cystectomy for muscle invasive bladder cancer: A population-based analysis. J Clin Oncol 2018;36:503.
Martini A, Jia R, Ferket BS, Waingankar N, Plimack ER, Crabb SJ, et al. Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer. Cancer 2019;125:3155-63.
Motterle G, Andrews JR, Morlacco A, Karnes RJ. Predicting response to neoadjuvant chemotherapy in bladder cancer. Eur Urol Focus 2020;6:642-9.
Shannon C, Crombie C, Brooks A, Lau H, Drummond M, Gurney H. Carboplatin and gemcitabine in metastatic transitional cell carcinoma of the urothelium: effective treatment of patients with poor prognostic features. Ann Oncol 2001;12:947-52.
Nogué-Aliguer M, Carles J, Arrivi A, Juan O, Alonso L, Font A, et al. Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. Cancer 2003;97:2180-6.
Park JH, Lee SW, Kim HS, Kang SG, Ko YH, Kim ST, et al. Combination of gemcitabine and carbo- platin as first line treatment in elderly patients or those unfit for cisplatin-based chemotherapy with advanced transitional cell carcinoma of the urinary tract. Cancer Chemother Pharmacol 2013;71:1033-9.
Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol 2007;52:134-41.
Bellmunt J, de Wit R, Albanell J, Baselga J. A feasi- bility study of carboplatin with fixed dose of gemcitabine in “unfit” patients with advanced bladder cancer. Eur J Cancer 2001;37:2212-5.
Linardou H, Aravantinos G, Efstathiou E, Kalofonos C, Anagnostopoulos A, Deliveliotis C, et al. Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: phase II study of the Hellenic Co-operative Oncology Group. Urology 2004;64:479-84.
Ryan Pritchard E, Waddell JA, Solimando DA, Jr. Gemcitabine and carboplatin (renally dosed) regi- men for bladder cancer. Hosp Pharm 2015;50:103-7.
Iwasaki K, Obara W, Kato Y, Takata R, Tanji S, Fujioka T. Neoadjuvant gemcitabine plus carboplatin for locally advanced bladder cancer. Jpn J Clin Oncol 2013;43:193-9.
Koie T, Ohyama C, Hashimoto Y, Hatakeyama S, Yamamoto H, Yoneyama T, et al. Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study. Int J Clin Oncol 2013;18:724-30.
Murasawa H, Koie T, Ohyama C, Yamamoto H, Imai A, Hatakeyama S, et al. The utility of neoadjuvant gemcitabine plus carboplatin followed by immediate radical cystectomy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy. Int J Clin Oncol 2017;22:159-65.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-13.
Liu W, Tian J, Zhang S, Yang E, Shen H, Li F, et al. The utilization status of neoadjuvant chemotherapy in muscle-invasive bladder cancer: a systematic review and meta-analysis. Minerva Urol Nephrol 2021;7:144-53.
Pignot G, Houédé N, Roumiguié M, Audenet F, Brunelle S,Colin P,et al. [ypT0N0afterneoadjuvant chemotherapy and cystectomy for muscle-invasive bladder cancer: Incidence and prognosis. A review from the Bladder group of the French Committee of Oncology]. Prog Urol 2018;28:567-74.
Yin M, Joshi M, Meijer RP, Glantz M, Holder S, Harvey HA, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist 2016; 21:708-15.
Pokuri VK, Syed JR, Yang Z, Field EP, Cyriac S, Pili R, et al. Predictors of complete pathologic response (pt0) to neoadjuvant chemotherapy in muscle-invasive bladder carcinoma. Clin Genitourin Cancer 2016;14:e59-65.
Boeri L, Soligo M, Frank I, Boorjian SA, Thompson RH, Tollefson M, et al. Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle-invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy and radical cystectomy: a single-centre experience. BJU Int 2019;123:1011-9.
Buisan O, Orsola A, Areal J, Font A, Oliveira M, Martinez R, et al. Low pretreatment neutrophil-to-lymphocyte ratio predicts for good outcomes in patients receiving neoadjuvant chemotherapy before radical cystectomy for muscle invasive bladder cancer. Clin Genitourin Cancer 2017;15:145-51.e2.
Black AJ, Zargar H, Zargar-Shoshtari K, Fairey AS, Mertens LS, Dinney CP, et al. The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy. Urol Oncol 2020;38:3.e17-3.e27.
Knight K, Wade S, Balducci L. Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med 2004;116:11-26s.
Xia L, Guzzo TJ. Preoperative anemia and low hemoglobin level are associated with worse clinical outcomes in patients with bladder cancer undergoing radical cystectomy: a meta-analysis. Clin Genitourin Cancer 2017;15:263-72.e4.
Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline. J Urol 2016;196:1021-9.
Boonnam S, Panumatrassamee K, Opanuraks J, Santingamkun A, Tantiwongse K, Ratchanon S, et al. Perioperative outcomes of open radical cystectomy in bladder carcinoma: King Chulalongkorn Memorial Hospital experiences. Chula Med J 2016;60:1-12.
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