The role of radiotherapy in metastatic bladder cancer

Abstract

The management of metastatic bladder cancer is palliative. Best outcomes are achieved in those who are fit enough for systemic therapies. The place of radiotherapy in these patients is mainly for symptom control, in particular haematuria. However, a small proportion, especially those with oligometastases, will benefit from more radical treatment. In this review, we look at the evidence currently available for radiotherapy in this setting.

Keywords

Bladder cancer / radiotherapy / oligo metastases / haematuria / bone metastases / brain metastases

References

[1] Antoni S,Soerjomataram I,Jemal A.Bladder cancer incidence and mortality: a global overview and recent trends.Eur Urol2017;71:96-108

[2] Bray F,Soerjomataram I,Torre LA.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2018;68:394-424

[3] Cancer Research UK. Bladder cancer. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer [Last accessed on 14 Jan 2021]

[4] Ghoneim MA,el-Mekresh M.Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later.J Urol2008;180:121-7

[5] Mari A,Tellini R.Patterns and predictors of recurrence after open radical cystectomy for bladder cancer: a comprehensive review of the literature.World J Urol2018;36:157-70 PMCID:PMC5799348

[6] Witjes JA,Cathomas R. Members of the European Association of Urology (EAU) Guidelines Panel EAU Guidelines on muscle invasive and metastatic bladder cancer. Available from: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/ [Last accessed on 14 Jan 2021]

[7] von der Maase H,Roberts JT.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 Oncol2005;23:4602-8

[8] Balar AV,Rosenberg JE.Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.Lancet2017;389:67-76 PMCID:PMC5568632

[9] Powles T,Voog E.Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma.N Engl J Med2020;383:1218-30

[10] Sternberg CN,Schornagel JH.EORTC Genito-Urinary Cancer GroupSeven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.Eur J Cancer2006;42:50-4

[11] Abe T,Obara W.Outcome of metastasectomy for urothelial carcinoma: a multi-institutional retrospective study in Japan.J Urol2014;191:932-6

[12] Kim T,You D.Pulmonary metastasectomy could prolong overall survival in select cases of metastatic urinary tract cancer.Clin Genitourin Cancer2015;13:e297-304

[13] Patel V,Stern A.Survival after metastasectomy for metastatic urothelial carcinoma: a systematic review and meta-analysis.Bladder Cancer2017;3:121-32 PMCID:PMC5409038

[14] Abufaraj M,Daneshmand S.The role of surgery in metastatic bladder cancer: a systematic review.Eur Urol2018;73:543-57 PMCID:PMC8177016

[15] Siefker-Radtke AO,Pisters LL.Is there a role for surgery in the management of metastatic urothelial cancer?.J Urol2004;171:145-8

[16] Iwamoto H,Shimura Y.Metastasectomy improves survival in patients with metastatic urothelial carcinoma.Anticancer Res2016;36:5557-61

[17] Lydon A.How should we palliate bladder cancer?.Clin Oncol (R Coll Radiol)1992;4:273-4

[18] Ali A,Mehta S.Palliative radiation therapy in bladder cancer-importance of patient selection: a retrospective multicenter study.Int J Radiat Oncol Biol Phys2019;105:389-93

[19] Duchesne GM,Griffiths GO.A randomized trial of hypofractionated schedules of palliative radiotherapy in the management of bladder carcinoma: results of medical research council trial BA09.Int J Radiat Oncol Biol Phys2000;47:379-88

[20] McLaren DB,Mason MD.Hypofractionated radiotherapy for muscle invasive bladder cancer in the elderly.Radiother Oncol1997;43:171-4

[21] Kouloulias V,Kolliarakis N,Kelekis N.Evaluation of acute toxicity and symptoms palliation in a hypofractionated weekly schedule of external radiotherapy for elderly patients with muscular invasive bladder cancer.Int Braz J Urol2013;39:77-82

[22] Jose CC,Norman A.Hypofractionated radiotherapy for patients with carcinoma of the bladder.Clin Oncol (R Coll Radiol)1999;11:330-3

[23] Dirix P,Joniau S,Haustermans K.Hypofractionated palliative radiotherapy for bladder cancer.Support Care Cancer2016;24:181-6

[24] Fosså SD.Short-term moderate-dose pelvic radiotherapy of advanced bladder carcinoma. A questionnaire-based evaluation of its symptomatic effect.Acta Oncol1991;30:735-8

[25] Bianchi M,Becker A.Age-stratified distribution of metastatic sites in bladder cancer: a population-based analysis.Can Urol Assoc J2014;8:E148-58 PMCID:PMC3956834

[26] Necchi A,Pal SK.Retrospective International Study of Invasive/Advanced Cancer of the Urothelium GroupBone metastases as the only metastatic site in patients with urothelial carcinoma: focus on a special patient population.Clin Genitourin Cancer2018;16:e483-90 PMCID:PMC7974827

[27] Shinagare AB,Jagannathan JP,Taplin ME.Metastatic pattern of bladder cancer: correlation with the characteristics of the primary tumor.AJR Am J Roentgenol2011;196:117-22

[28] Rich SE,Raman S.Update of the systematic review of palliative radiation therapy fractionation for bone metastases.Radiother Oncol2018;126:547-57

[29] Chow R,Schild SE.Single vs multiple fraction palliative radiation therapy for bone metastases: cumulative meta-analysis.Radiother Oncol2019;141:56-61

[30] Chow R,Hollenberg D.Efficacy of single fraction conventional radiation therapy for painful uncomplicated bone metastases: a systematic review and meta-analysis.Ann Palliat Med2017;6:125-42

[31] Chow R,Chan S.Efficacy of multiple fraction conventional radiation therapy for painful uncomplicated bone metastases: a systematic review.Radiother Oncol2017;122:323-31

[32] Niewald M,Abel U.Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.Int J Radiat Oncol Biol Phys36:1085-9

[33] Madsen EL.Painful bone metastasis: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy X 6 versus 10 Gy X 2.Int J Radiat Oncol Biol Phys1983;9:1775-9

[34] Anter A.Single fraction versus multiple fraction radiotherapy for treatment of painful bone metastases: a prospective study; Mansoura experience.Forum Clin Oncol2015;6:8-13

[35] Hoskin P,Fidarova E.IAEA randomised trial of optimal single dose radiotherapy in the treatment of painful bone metastases.Radiother Oncol2015;116:10-4

[36] Roos DE,O'Brien PC.Trans-Tasman Radiation Oncology GroupTROG 9605. Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05).Radiother Oncol2005;75:54-63

[37] Foro Arnalot P,Galcerán JC.Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction.Radiother Oncol2008;89:150-5

[38] Okawa T,Goto M,Miyaji N.Randomized prospective clinical study of small, large and twice-a-day fraction radiotherapy for painful bone metastases.Radiother Oncol1988;13:99-104

[39] Nielsen OS,Sandberg E,Timothy AR.Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases.Radiother Oncol1998;47:233-40

[40] Steenland E,van Houwelingen H.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol1999;52:101-9

[41] Price P,Easton D,Palmer S.Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases.Radiother Oncol1986;6:247-55

[42] Cole DJ.A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases.Clin Oncol (R Coll Radiol)1989;1:59-62

[43] Gaze MN,Kerr GR.Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.Radiother Oncol1997;45:109-16

[44] Majumder D,Bandyopadhyay A,Sarkar SK.Single fraction versus multiple fraction radiotherapy for palliation of painful vertebral bone metastases: a prospective study.Indian J Palliat Care2012;18:202-6 PMCID:PMC3573475

[45] Hartsell WF,Bruner DW.Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.J Natl Cancer Inst2005;97:798-804

[46] Gutiérrez Bayard L, Salas Buzón Mdel C, Angulo Paín E, de Ingunza Barón L. Radiation therapy for the management of painful bone metastases: results from a randomized trial.Rep Pract Oncol Radiother2014;19:405-11 PMCID:PMC4201774

[47] Badzio A,Jereczek-Fossa BA.20 Gy in five fractions versus 8Gy in one fraction in palliative radiotherapy of bone metastases. A multicentre randomized study.Nowotwory2003;53:261-4

[48] Amouzegar-Hashemi F,Kazemian A,Haddad P.Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients.Curr Oncol2008;15:151 PMCID:PMC2442760

[49] Berwouts D,Lambert B.Biological 18[F]-FDG-PET image-guided dose painting by numbers for painful uncomplicated bone metastases: a 3-arm randomized phase II trial.Radiother Oncol2015;115:272-8

[50] 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party.Radiother Oncol1999;52:111-21

[51] Güden M,Ulutin C.Six gray single dose radiotherapy in the treatment of metastatic bone pain.Tohoku J Exp Med2002;197:111-4

[52] Hayashi S,Hoshi H.External beam radiotherapy for painful bone metastases from hepatocellular carcinoma: multiple fractions compared with an 8-Gy single fraction.Nagoya J Med Sci2014;76:91-9 PMCID:PMC4345724

[53] Hoskin PJ,Easton D,Austin D,Yarnold JR.A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain.Radiother Oncol1992;23:74-8

[54] Jeremic B,Acimovic L.A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.Int J Radiat Oncol Biol Phys1998;42:161-7

[55] Nuzzo M,Torre G.Single fraction radiotherapy (8 Gy) on painful bone metastases with involvement of the adjacent soft tissues.Radiother Oncol2015;115:S697-8

[56] Price P,Easton D,Palmer S.Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.Radiother Oncol1988;12:297-300

[57] Uppelschoten JM,de Jong JM.Single-dose radiotherapy (6 Gy): palliation in painful bone metastases.Radiother Oncol1995;36:198-202

[58] Diamantopoulos LN,Sonpavde GP.Central nervous system metastasis in patients with urothelial carcinoma: institutional experience and a comprehensive review of the literature.Clin Genitourin Cancer2020;18:e266-76 PMCID:PMC7272305

[59] Patchell RA,Regine WF.Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.JAMA1998;280:1485-9

[60] Rosenstein M,Scher H.Treatment of brain metastases from bladder cancer.J Urol1993;149:480-3

[61] Mahmoud-Ahmed AS,Kupelian PA,Peereboom DM,Barnett GH.Brain metastases from bladder carcinoma: presentation, treatment and survival.J Urol2002;167:2419-22

[62] Roos DE,Burmeister BH.Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05).Radiother Oncol2006;80:318-22

[63] Kocher M,Abacioglu U.Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.J Clin Oncol2011;29:134-41 PMCID:PMC3058272

[64] Tsao M,Sahgal A.A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases.Cancer2012;118:2486-93

[65] Brown PD,Cerhan JH.Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.Lancet Oncol2017;18:1049-60 PMCID:PMC5568757

[66] Fokas E,Engenhart-Cabillic R.A comparison of radiotherapy with radiotherapy plus surgery for brain metastases from urinary bladder cancer: analysis of 62 patients.Strahlenther Onkol2010;186:565-71

[67] Khuntia D,Li J.Whole-brain radiotherapy in the management of brain metastasis.J Clin Oncol2006;24:1295-304

[68] Borgelt B,Larson M,Griffin T.Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: Final results of the first two studies by the radiation therapy oncology group.Int J Radiat Oncol Biol Phys1981;7:1633-8

[69] Mulvenna P,Barton R.Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.Lancet2016;388:2004-14 PMCID:PMC5082599

[70] Seisen T,Leow JJ.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 Oncol2016;34:3529-36

[71] Dong F,Gao F.Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study.Cancer Manag Res2017;9:611-26 PMCID:PMC5694197

[72] Bajorin DF,Mazumdar M.Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.J Clin Oncol1999;17:3173-81

[73] Tan MP,Warren-Oseni K.The intensity-modulated pelvic node and bladder radiotherapy (IMPART) trial: a phase II single-centre prospective study.Clin Oncol (R Coll Radiol)2020;32:93-100 PMCID:PMC6966321

[74] Fackrell DG,Chetiyawardana S,James N.The delivery of radical radiotherapy to the bladder and pelvis in node-positive (N1) bladder cancer: a five patient case series.BJR Case Rep2017;3:20160102 PMCID:PMC6159232

[75] Søndergaard J,Petersen JB,Grau C.The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy.Acta Oncol2009;48:238-44

[76] Amin MB,Greene F. (Eds.). AJCC cancer staging manual (8th edition). Springer International Publishing: American Joint Commission on Cancer; 2017.

[77] Galsky MD,Krege S.Nomogram for predicting survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy.Cancer2013;119:3012-9

[78] Palma DA,Harrow S.Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.Lancet2019;393:2051-8

[79] Palma D,Harrow S.Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET randomized trial.Int J Radiat Oncol Biol Phys2020;108:S88-9 PMCID:PMC7460150

[80] Chalkidou A,Grzeda MT.Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study.Lancet Oncol2021;22:98-106

[81] Sutera P,Kalash R.Initial results of a multicenter phase 2 trial of stereotactic ablative radiation therapy for oligometastatic cancer.Int J Radiat Oncol Biol Phys2019;103:116-22

[82] Lee YH,Choi HS.Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.Thorac Cancer2018;9:1671-9 PMCID:PMC6275814

[83] Ost P,Decaestecker K.Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial.J Clin Oncol2018;36:446-53

[84] Leonetti A,Baldari G.Radiotherapy for the treatment of distant nodes metastases from oligometastatic urothelial cancer: a retrospective case series.Int J Urol2018;25:879-86

[85] Augugliaro M,Ciardo D.Recurrent oligometastatic transitional cell bladder carcinoma: is there room for radiotherapy?.Neoplasma2019;66:160-5

[86] Shah S,Hancock S,Skinner E.Consolidative radiotherapy in metastatic urothelial cancer.Clin Genitourin Cancer2017;15:685-8

[87] Abe T,Harabayashi T.Prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients receiving systemic chemotherapy.Jpn J Clin Oncol2020;50:206-13

[88] Franzese C,Nicosia L,Livi L.Stereotactic body radiation therapy in the management of oligometastatic and oligoprogressive bladder cancer and other urothelial malignancies.Clin Oncol (R Coll Radiol)2021;33:50-6

[89] Ukleja J,Miyamoto DT.Immunotherapy combined with radiation therapy for genitourinary malignancies.Front Oncol2021;11:663852 PMCID:PMC8141854

[90] Joshi M,Kaag M.Phase Ib study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with urothelial cancer of the bladder: BTCRC-GU15-023 study.J Clin Oncol2018;36:455

[91] Joshi M,Kaag M.Concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in patients with locally advanced urothelial cancer of bladder (DUART): Btcrc-GU15-023.J Clin Oncol2020;38:513

[92] Bethesda (MD): national library of medicine (US). Identifier NCT03115801, a phase II randomized trial of immunotherapy plus radiotherapy in metastatic genitourinary cancers. Available from: http://clinicaltrials.gov/ct/show/NCT0311580 order=1 [Last accessed on 14 Jan 2021]