Document Type : Original Article

Authors

1 Medical Oncology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

2 Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Suez Canal University, Egypt

3 Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt

4 Department of Radiation Therapy Princess Nourah Bint Abdulrhman University, Zagazig, Egypt

Abstract

Background: Neoadjuvant chemotherapy (NAC) grants a modest survival benefit in localized muscle-invasive bladder cancer (MIBC). We evaluated the pathological response and survival outcome after NAC in stage II and IIIA MIBC and their correlation with body mass index (BMI).
Method: Our retrospective study included stage II (T2 N0) and IIIA (T3 N0, T4 N0, T1-4 N1) MIBC. They received NAC followed by radical cystectomy. The patients were categorized into level I: a BMI of 18.5 – 24.9 kg/m2, level II: a BMI of 25-29.9 kg/m2, and level III: a BMI of ≥ 30 kg/m2.
Results: 103 patients with localized MIBC were included. The median age was 63 years; 35 patients (34.0%) belonged to level I, 40 patients (38.8%) belonged to level II, and 28 patients (27.2%) belonged to level III. Smoking status was more common in level II (51.0%) and level III (36.7%) (P < 0.001). Only 18 patients had ECOG PS 2, all belonging to level III (P < 0.001). After NAC, the pCR was 34.3%, 25%, and 10.7% of level I, level II, and level III (P = 0.03), respectively. Of 19 patients who passed away, 10 patients belonged to level III and 6 patients belonged to level II (P = 0.007). For level I, level II, and level III, the disease-free survival was 23.2 months, 12.7 months, and 10.7 months and the overall survival was 61.9, 52.3, and 28.7 months, respectively.
Conclusion: Obesity and overweight could be predictive and prognostic markers in localized MIBC. These factors are associated with low pCR after NAC, poor disease-free survival, and overall survival.

Keywords

How to cite this article:

Mohammed A, Elsayed F, Salem R. The impact of body mass index on pathological response and survival outcome after neoadjuvant chemotherapy in localized bladder cancer. Middle East J Cancer. 2023;14(1):136-45. doi: 10. 30476/mejc.2022.90799.1591.

  1. Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211-7. doi: 10.1016/j.ccr.2005.02.013.
  2. Hopkins BD, Goncalves MD, Cantley LC. Obesity and cancer mechanisms: Cancer metabolism. J Clin Oncol. 2016;34(35):4277-83. doi: 10.1200/JCO.2016. 67.9712.
  3. Nuttall FQ. Body mass index: Obesity, BMI, and health: A critical review. Nutr Today. 2015;50(3):117- 28. doi: 10.1097/NT.0000000000000092.
  4. Song M, Giovannucci E. Estimating the influence of obesity on cancer risk: Stratification by smoking is critical. J Clin Oncol. 2016;34(27):3237-9. doi: 10.1200/JCO.2016.67.6916.
  5. Hursting SD, Digiovanni J, Dannenberg AJ, Azrad M, Leroith D, Demark-Wahnefried W, et al. Obesity, energy balance, and cancer: new opportunities for prevention. Cancer Prev Res (Phila). 2012;5(11):1260- 72. doi: 10.1158/1940-6207.CAPR-12-0140.
  6. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet. 2014;384(9945): 755-65. doi: 10.1016/S0140-6736(14)60892-8.
  7. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-38. doi: 10.1056/ NEJMoa021423.
  8. Fang X, Wei J, He X, Lian J, Han D, An P, et al. Quantitative association between body mass index and the risk of cancer: A global meta-analysis of prospective cohort studies. Int J Cancer. 2018;143(7): 1595-603. doi: 10.1002/ijc.31553.
  9. Lavery HJ, Stensland KD, Niegisch G, Albers P, Droller MJ. Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: a useful surrogate. J Urol. 2014;191(4):898-906. doi: 10.1016/j.juro.2013.10.142.
  10. Bhindi B, Frank I, Mason RJ, Tarrell RF, Thapa P, Cheville JC, et al. Oncologic outcomes for patients with residual cancer at cystectomy following neoadjuvant chemotherapy: A pathologic stagematched analysis. Eur Urol. 2017;72(5):660-4. doi: 10.1016/j.eururo.2017.05.016.
  11. Peyton CC, Tang D, Reich RR, Azizi M, Chipollini J, Pow-Sang JM, et al. Downstaging and survival outcomes associated with neoadjuvant chemotherapy regimens among patients treated with cystectomy for muscle-invasive bladder cancer. JAMA Oncol. 2018;4(11):1535-42. doi: 10.1001/jamaoncol. 2018.3542.
  12. Lee RK, Abol-Enein H, Artibani W, Bochner B, Dalbagni G, Daneshmand S, et al. Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes. BJU Int. 2014;113(1): 11-23. doi: 10.1111/bju.12121.
  13. Leow JJ, Martin-Doyle W, Fay AP, Choueiri TK, Chang SL, Bellmunt J. A systematic review and metaanalysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol. 2014;66(3):529-41. doi: 10.1016/j.eururo.2014.03.003.
  14. Dare S, Mackay DF, Pell JP. Relationship between smoking and obesity: a cross-sectional study of 499,504 middle-aged adults in the UK general population. PLoS One. 2015;10(4):e0123579. doi: 10.1371/journal. pone.0123579. Erratum in: PLoS One. 2017;12 (2):e0172076.
  15. Choi JB, Lee EJ, Han KD, Hong SH, Ha US. Estimating the impact of body mass index on bladder cancer risk: Stratification by smoking status. Sci Rep. 2018;8(1):947. doi: 10.1038/s41598-018-19531-7.
  16. Watanabe T, Tsujino I, Konno S, Ito YM, Takashina C, Sato T, et al. Association between smoking status and obesity in a Nationwide Survey of Japanese Adults. PLoS One. 2016;11(3):e0148926. doi: 10.1371/journal.pone.0148926.
  17. Courtemanche C, Tchernis R, Ukert B. The effect of smoking on obesity: Evidence from a randomized trial. J Health Econ. 2018;57:31-44. doi: 10.1016/j.jhealeco.2017.10.006.
  18. Santana CCA, Hill JO, Azevedo LB, Gunnarsdottir T, Prado WL. The association between obesity and academic performance in youth: a systematic review. Obes Rev. 2017;18(10):1191-9. doi: 10.1111/obr.12582.
  19. Wu N, Chen Y, Yang J, Li F. Childhood obesity and academic performance: The role of working memory. Front Psychol. 2017;8:611. doi: 10.3389/fpsyg. 2017.00611.
  20. Farooq A, Gibson AM, J Reilly J, Gaoua N. The association between obesity and cognitive function in otherwise healthy premenopausal Arab women. J Obes. 2018;2018:1741962. doi: 10.1155/2018/ 1741962.
  21. Schinzari G, Monterisi S, Pierconti F, Nazzicone G, Marandino L, Orlandi A, et al. Neoadjuvant Chemotherapy for patients with muscle-invasive urothelial bladder cancer candidates for curative surgery: A prospective clinical trial based on cisplatin feasibility. Anticancer Res. 2017;37(11):6453-8. doi: 10.21873/anticanres.12100.
  22. Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, et al. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015;121(15):2586-93. doi: 10.1002/cncr.29387.
  23. Yuh BE, Ruel N, Wilson TG, Vogelzang N, Pal SK. Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer. J Urol. 2013;189(5):1682-6. doi: 10.1016/j.juro.2012.10.120.
  24. Chromecki TF, Cha EK, Fajkovic H, Rink M, Ehdaie B, Svatek RS, et al. Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy. BJU Int. 2013;111(2):249-55. doi: 10.1111/j.1464-410X.2012.11322.x.
  25. Ferro M, Vartolomei MD, Russo GI, Cantiello F, Farhan ARA, Terracciano D, et al. An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer. World J Urol. 2019;37(3):507-14. doi: 10.1007/s00345-018-2397-1.
  26. Batty GD, Shipley MJ, Jarrett RJ, Breeze E, Marmot MG, Smith GD. Obesity and overweight in relation to organ-specific cancer mortality in London (UK): findings from the original Whitehall study. Int J Obes (Lond). 2005;29(10):1267-74. doi: 10.1038/sj.ijo. 0803020.
  27. Lin Y, Wang Y, Wu Q, Jin H, Ma G, Liu H, et al. Association between obesity and bladder cancer recurrence: A meta-analysis. Clin Chim Acta. 2018; 480:41-6. doi: 10.1016/j.cca.2018.01.039.
  28. Kwon T, Jeong IG, You D, Han KS, Hong S, Hong B, et al. Obesity and prognosis in muscle-invasive bladder cancer: the continuing controversy. Int J Urol. 2014;21(11):1106-12. doi: 10.1111/iju.12530.
  29. Maurer T, Maurer J, Retz M, Paul R, Zantl N, Gschwend JE, et al. Influence of body mass index on operability, morbidity and disease outcome following radical cystectomy. Urol Int. 2009;82(4):432-9. doi: 10.1159/000218533.
  30. Freedland SJ, Bañez LL, Sun LL, Fitzsimons NJ, Moul JW. Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database. Prostate Cancer Prostatic Dis. 2009;12(3):259-63. doi: 10.1038/pcan.2009.11.
  31. Guo JY, White E. Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors. Autophagy. 2013;9(10):1636-8. doi: 10.4161/auto.26123.
  32. Harris FT, Rahman SM, Hassanein M, Qian J, Hoeksema MD, Chen H, et al. Acyl-coenzyme Abinding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer. Cancer Prev Res (Phila). 2014;7(7):748-57. doi: 10. 1158/1940-6207.CAPR-14-0057.
  33. Rodríguez-Enríquez S, Hernández-Esquivel L, Marín- Hernández A, El Hafidi M, Gallardo-Pérez JC, Hernández-Reséndiz I, et al. Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int J Biochem Cell Biol. 2015;65:209-21. doi: 10.1016/j.biocel. 2015.06.010.
  34. Schlaepfer IR, Rider L, Rodrigues LU, Gijón MA, Pac CT, Romero L, et al. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. Mol Cancer Ther. 2014;13(10):2361-71. doi: 10.1158/1535- 7163.MCT-14-0183.
  35. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498- 503. doi: 10.1038/nm.2492.
  36. Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013;1831(10): 1533-41. doi: 10.1016/j.bbalip.2013.02.010.
  37. Prado CM, Cushen SJ, Orsso CE, Ryan AM. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact. Proc Nutr Soc. 2016;75(2):188- 98. doi: 10.1017/S0029665115004279.
  38. Zhou BF; Cooperative Meta-Analysis Group of the Working Group on Obesity in China. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults-- study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002;15(1):83-96.
  39. Horowitz NS, Wright AA. Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies. Gynecol Oncol. 2015;138(1):201-6. doi: 10.1016/j.ygyno.2015.04.002.
  40. Sparreboom A, Wolff AC, Mathijssen RH, Chatelut E, Rowinsky EK, Verweij J, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol. 2007;25(30):4707-13. doi: 10.1200/JCO.2007.11.2938.