Шаблоны LeoTheme для Joomla.
GavickPro Joomla шаблоны

radiation banner

Review Article

Bladder Cancer Treatment: Review of Literature

Parisi S.1, Morelli F.², Maiello E.², Cisternino A.³, Troiano M.1, Corsa P.1, Raguso A.1, Cossa S.1, Clemente M.A.1, Donno E.1, Parisi F.4, Munafò T.1, Valle G.5,Cecere A.6, Guglielmi G.6-7.

1Department of Radiation Oncology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
2Department of Medical Oncology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
3Department of Urology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
4Student of University Chieti. Faculty of Medicine, Viale dei Vestini, Italy
5Department of Nuclear Medicine, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
6Department of Radiology, University of Foggia, Viale Luigi Pinto 1, 71100 Foggia, Italy
7Department of Radiology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy

*Corresponding author: Dr. Guglielmi Giuseppe, MD, Department of Radiology, University of Foggia, Viale Luigi Pinto 1, 71100 Foggia, Italy; Department of Radiology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy, Tel.: + 39 0882 410686;
E-mail: giuseppe.guglielmi@unifg.it

Submitted: 03-23-2015 Accepted: 05-07-2015 Published: 05-26-2015

Download PDF

_________________________________________________________________________________________________________________________

 

Article

Abstract

Purpose

The aim of this study is the systematic review of external radiation therapy studies in bladder cancers.

The review of the literature is based on data from meta-analyses, randomized and prospective trials and retrospective studies.
There are several reports on multimodal treatment in invasive bladder cancer: intravesical chemotherapy, surgery, neoadjuvant
chemotherapy, radiotherapy and concomitant radiochemotherapy with organ preservation.

Conclusions

Sufficient data now exist to demonstrate that conservative management with organ preservation is a valuable alternative to
radical cystectomy, the traditional gold standard, in invasive bladder cancer.

Keywords: Invasive Bladder Cancer; Treatment; Radiation Therapy; Radical Cystectomy;Chemotherapy; Overall Survival

Abbreviations

CDDP : Cis-diamminedichloroplatinum as Cisplatin
CCRT : Concomitant Chemioradiotherapy
CR : Complete Response
CT : Chemotherapy
CTV : Clinical Target Volume
DFS : Disease Free Survival
DSS : Disease Specific Survival
FFDM : Freedom from Distant Metastases
IMRT : Intensity Modulated Radiation Therapy
LF : Local-Regional Failures
MCV : Methotrexate, Cisplatin and Vinblastine
MVAC : Methotrexate, Vinblastine, Doxorubicin and Cisplatin
OARs : Organs at Risk
OS : Overall Survival
pCR : Pathological Complete Response
RTOG : Radiation Therapy Oncology Group
RT : Radiotherapy
TURBT : Transurethral Resection of Bladder Tumors
5-FU : 5- fluorouracil

Introduction

Most bladder cancers are transitional cell carcinomas. In 2014 in USA the incidence of new cases and deaths were 74.690 and 15.580 respectively [1].Worldwide, almost 430.000 cases were diagnosed in 2012 [2]. Bladder cancer is the 13th most common cause of cancer death worldwide, with around 165.100 deaths from bladder cancer in 2012 [3].

The successful therapy of bladder cancer was obtained with great economic burden in health care system [4] with cost from $ 96.000 to 187.000 per patients.

Incidence of bladder cancer increases with age: the median age at the diagnosis is 73 years; in fact, 70% of diagnosis occurs in patients aged 65 and older, and half of diagnosis occurs in patients older than 75 [5].

There are not many clinical studies about old patients affected by bladder cancer because comorbidity and higher risk of collateral effects of standard therapy limited their eligibility in protocols. The solution of optimal treatment should be personalized and informed by a full assessment able to predict probability incidence of side effects [6].

A comprehensive literature research was conducted using PubMed in July 2014. Relevant international articles published from 1970s to 2014 were assessed. The keywords for search purpose were: invasive bladder cancer, radiation therapy, radical cystectomy, chemotherapy, overall survival.


There are several reports on multimodal treatment in invasive bladder cancer: intravesical chemotherapy, surgery, neoadjuvant chemotherapy (CT) and radiotherapy (RT) or concomitant radiochemotherapy (CCRT) with organ preservation.

Radical cystectomy

Radical cystectomy with bilateral pelvic lymph node dissection followed by urinary diversion remains the gold standard for treating muscle-invading bladder cancer. Potential morbidity and mortality are described in literature, mainly in old patients. The study conducted by Froehner et al. showed that perioperative mortality [7] was 3-4% in 80 years old patients; conversely in young patients was 1-2%. Also post operative complications are higher in older patients. For this reason, the use of lymphadenectomy and neobladder intervention is less common in older people.

New robotic techniques or laparoscopic techniques of cystectomy are more utilized with less blood loss during surgery and short stay in hospital.

Comparison of large surgery and RT series suggests very similar long-term survival rates. However must surgical series have median age of 60 and RT series 60-80.

Bladder preservation is different in the world (10% in U.S, 25% in Sweden, 50% in U.K.) [8-10].

James in U.K.[8] showed that in patients 80 years old only 3 % went to surgery, instead 55% underwent to RT.

Munro in U.K. [9] demonstrated that in Yorkshire the ratio of surgery was 1:3; after 10 years 22% were treated with RT and 24% underwent to radical cystectomy.

Definitive Radiotherapy

RT alone applied with a curative intent was used extensively from the 1950s through the 1980s. It was inevitable that numerous studies attempted a comparison of outcome of RT with radical cystectomy. Such comparisons were very difficult, because patients selected for radical cystectomy had less advanced tumors at diagnosis, they were younger and in a better general condition than patients selected for definitive irradiation. Patients treated by radical RT should have adequate bladder capacity, no stenotic symptoms and no incontinence (Figure 1).

rad fig 18.1

Figure 1. A digitally reconstructed radiographs, and dosimetric study of bladder irradiation.

Results reported in the literature are not significant: the 5-year survival rate for patients treated with RT alone (dose of 60–66 Gy at a 1.8- to 2-Gy daily fraction) is 32% (range 22%–50%) [11,12] (Table 1). A recent review of treatment outcomes in RT -treated patients showed that the following 5-year survival rates were different in according to the patients’staging: T1, 35%–71%; T2, 10%–59%; T3, 10%–38%; and T4, 0%–16% [14].

rad table 18.1

Table 1. Survival after RT alone for muscle-invasive bladder cancer.

Preoperative radiation therapy

The largest experience (338 patients) with preoperative RT obtained pathologic downstaging in 65% of patients and complete response (CR) in 42%. The 5-year overall survival (OS) was 44% and the pelvic and distant recurrence rates were 16% and 43%, respectively [28]. A prospective randomized trial comparing preoperative RT with definitive pelvic irradiation was conducted by Bloom et al. [31]. The 5-year survival in patients receiving RT followed by cystectomy was 38% versus 29% for those treated with RT alone (not statistically significant). There was a significant survival benefit of preoperative irradiation in male patients younger than 60 years of age. Tumor- stage reduction and CR were obtained in 49% and 31% of patients, respectively, receiving preoperative RT.

Strong support for the use of preoperative irradiation in patients with T3b bladder cancer was reported by Cole et al. [32]: the 5-year local control in the preoperative group was 91% compared with 72% for those treated with radical cystectomy alone. There was also a benefit in terms of OS and disease free survival (DFS) and in freedom from distant metastases (FFDM) (not statically significant). Tumor doses were 20–50 Gy. However, a meta-analysis of five randomized trials showed no statistical difference in treatment outcomes between patients treated with preoperative RT and cystectomy alone [33]. A similar conclusion was reached in a phase III study of 140 patients comparing surgery alone with surgery and preoperative irradiation [34].

Preoperative CCRT showed better results than RT alone. In fact, in the Nordic Cystectomy Trial [35], the combination of CT (Adriamycin + Cisplatin (CDDP) for two cycles) plus RT (20 Gy in four fractions) followed by cystectomy showed a 5-year OS improvement of 15% only for T3-T4 disease compared with RT or surgery alone (p=0.03), whereas no survival benefit was found for early stages of disease (T1–T2). In the Canadian randomized study [36], concurrent CCDP improved pelvic disease control with preoperative or definitive RT compared with RT alone (p=0.038).

Postoperative radiation therapy

The main advantage of postoperative RT is the availability of pathological staging. Postoperative RT is administered to patients with extravesical disease, positive resection margins or involved pelvic lymph nodes with doses of 40–50 Gy.

Some studies reported reduction of the risk of pelvic recurrence from 30% to 50% to 10% to 20% [37-39], but some patients also received preoperative RT. Only one randomized study of radical cystectomy alone versus cystectomy and postoperative RT [40] reported a 5-year pelvic recurrence of 5% (50% in the cystectomy arm). The main disadvantage of postoperative RT is the high rate (20%–40%) of serious late gastrointestinal complications [37, 38, 41-43] for the larger volume of small bowel occupying the pelvis after cystectomy. Patients at high risk of recurrence are probably better treated with CT, which may prevent local and distant relapse and it is usually well tolerated.

An analysis of the University of Pennsylvania about cystectomy experience [44] identified three patient subgroups with significantly different local-regional failures (LF) risk: low-risk (stage ≤pT2 disease), intermediate-risk (stage ≥pT3 and ≥10 benign or malignant nodes removed at surgery), and high-risk (stage ≥pT3 and <10 benign or malignant nodes removed at surgery)—with 5-year LF rates of 8%, 23%, and 42%, respectively [45].

Postoperative radiation reduced pelvic recurrences in the past, but multiple reports showed excessive gastrointestinal toxicity using pre-1980 RT techniques. Modern RT, such as image-guided intensity modulated RT and proton therapy with more precisely targeted dose and greater normal tissue sparing, has prompted a re-evaluation of postoperative RT. These advanced techniques require knowledge of the specific patterns of failure after surgery to localize the clinical target volumes at risk. A research published by Baumann et al. in 2012 [45] wanted to identify the pattern of failure within the pelvis after cystectomy and the impact of stage, margin status, nodal status, and number of nodes removed on this pattern. RT should target at least the iliac/obturator nodes in stage ≥pT3 with negative margins; coverage of the presacral nodes and cystectomy bed may be necessary for stage ≥pT3 with positive margins [45].

Bladder-preservation therapy

The relative negative impact on quality of life for urinary diversion and the trend towards organ preservation led many authors to explore the role of conservative management.

Neoadjuvant CT compared with RT or surgery was investigated in an attempt to improve the results of surgery alone or definitive RT maintaining a functioning bladder.

In the European Organization for Research and Treatment of Cancer (EORTC)/Medical Research Council [46] trial, 976 patients undergoing curative cystectomy or radical RT were randomized to receive three cycles of neoadjuvant CT (CDDP, methotrexate and vinblastine (MCV)) in 491 patients or no CT in 485. The absolute difference between groups in 3-year OS of 5.5% (55.5% for CT versus 50% for no CT) was not statistically significant (p=0.075): neoadjuvant CT was associated with a higher pathological CR, but there was no clear evidence on survival. A recent meta-analysis [47] confirmed that neoadjuvant platinum-based combination CT reduces the mortality risk of 13%, with moderate improvement (5%, p=0.016) of 5-year OS, irrespective of the type of local treatment (surgery or RT alone or RT and cystectomy) and without differences between subgroups of patients. There was no evidence to support the use of single-agent platinum. These studies showed that patients
treated with RT (conservative approach) have preserved bladder function.

Over the past 15–20 years, several prospective trials investigated conservative therapy in which all patients were treated with transurethral resection of bladder tumors (TURBT) with or without CT followed by CCRT. For patients with CR, a consolidation RT or CCRT regimen was administered. Cystectomy was reserved for incomplete responders or recurrent disease. Many attempts have been made to combine RT (conventional or altered fractionation) with one or more chemotherapeutic agents in order to spare the bladder.

Since 1985, Radiation Therapy Oncology Group (RTOG) trials used a trimodal conservative treatment (TURBT, RT, CT) in patients with T2–T4a muscle invasive bladder cancer, eligible for cystectomy.

In three RTOG trials [48-50], patients were treated with neoadjuvant TURBT and CCRT (conventional or altered fractionation), whereas in two trials [51-52] patients were treatedwith induction by TURBT with or without CT and CCRT. Cystectomy was reserved for incompletely responders or relapse. In the RTOG 89-03 phase III study, the combination of neoadjuvant CT (MCV for 2 cycles) with CCRT failed to show significant benefits in terms of 5-year local control (61% versus 49%), OS (48% versus 49%) and FFDM (33% versus 39%) compared with CCRT alone, with more toxicity in the MCV arm [52]. In fact, subsequent studies by the RTOG emphasized the impact of adjuvant CT [MCV or CDDP + 5- fluorouracil (FU)] following RT (hypo- or hyperfractionated) [50], with good results at 3 years. Globally, 59%–75% of RTOG patients had CR after 24– 40 Gy of CCRT and received an additional boost of 20–25 Gy with concomitant CT. Twenty-five to 40% of patients required a radical cystectomy for incompletely responding or recurrent tumors. The 5-year OS was approximately 50%, with three fourths of those patients achieving a cure for their bladder cancer while maintaining a functioning bladder. Similar results were obtained by the Massachusetts General Hospital with the same schedules [53-54].

Two other important European universities pioneered modern bladder-preservation therapy based on TURBT followed by CCRT. Housset et al. from Paris began a prospective trial of preoperative CT using 5-FU and CDDP with concomitant RT (3 Gy b.i.d., total dose 24 Gy), followed by either cystectomy or additional CCRT. This treatment strategy resulted in a pathological CR of 77% and may be proposed as conservative treatment in patients with a CR to the initial course of CT [55]. These results were supported by the study of Rödel et al. [56], in which 415 patients were treated after TURBT with RT alone (126 patients) or combined with CDDP (240 patients) or CDDP + 5-FU (49 patients), with better CR rates for RT + CDDP – 5-FU (87%) compared with CDDP (66%) or RT alone (61%). Globally, OS at 5 years was 51%.

Similar results were obtained in further series of combined modality treatment for bladder preservation with excellent CR (~70%), and 5-year OS (~50%), with bladder preservation in most cases [48, 49, 53]. Table 2 summarizes the results of these studies [8,40,48–76].

In a recent meta-analysis of fifteen radiation series with different fractionation schedules and total doses, Pos et al. [77]

rad table 18.2

Table 2. Series of combined modality treatment for bladder preservation [76].

Abbreviations

CDDP : Cis-diamminedichloroplatinum as Cisplatin
CRT : Chemioradiotherapy
CT : Chemotherapy
MCV : Methotrexate, Cisplatin and Vinblastine
MGH : Massachusetts General Hospital
MVAC : Methotrexate, Vinblastine, Doxorubicin and Cisplatin
NG : Not given
OS : Overall survival
pCR : Pathological Complete Response
TURBT : Transurethral resection of bladder tumors
5-FU : 5- fluorouracil

found evidence for an overall dose–response relationship with an increase in local control by a factor of 1.44–1.47 for an increment in dose of 10 Gy. Hyperfractionated regimens allow an increase in total dose with reduced risk of late complications. A meta-analysis by Stuschke et al. [78] indicated that a hyperfractionated regimen showed an increased OS (odd ratio of death 0.55; p=0.002) and CR (odds ratio of failure 0.44; p=0.001).

Danesi et al. [70] reported the long-term results of a phase I/ II trial of CT (MCV) followed by concomitant CDDP + 5-FU and hyperfractionated irradiation (three 100- cGy fractions/day, for a total dose of 69 Gy). In a serie of 77 patients, the complete rate was 90%. The 5-year overall, bladder-intact, tumor-specific, disease-free and cystectomy-free survival rates for all 77 patients were 58.5%, 46.6%, 75%, 53.5% and 76.1%, respectively. Even if accelerated RT may overcome radioresistance due to tumor-cell repopulation, a recent randomized trial [79] reported no improvement of local control or survival rates but an increased acute bowel complications. Hypofractionated schedules have usually been used with palliative intent. There has been only one small phase III study of curative RT in which survival was inferior in the hypofractionated arm [80].

Some trials, in an attempt to improve results, explored the use of new chemotherapeutic agents and accelerated or hyperfractionated RT to increase irradiation dose in combination with CT. New chemotherapeutic agents, in particular gemcitabine and taxanes, are effective in combination with CDDP and RT (paclitaxel and gemcitabine are good radiosensitisers) [61, 74]. A recent Italian study [67] reported the feasibility of a combined scheme with gemcitabine (up to 400 mg/m2) plus CDDP and RT, obtaining 100% CR. Finally, the RTOG 99-06 trial introduced concomitant paclitaxel + CDDP plus bifractionated RT as induction treatment, followed by adjuvant CT (gemcitabine and CDDP) in patients with CR; no specific outcomes are yet available [57].

James ND et al. [8] recently showed, in a phase III randomized trial, very good results with one cycle of neoadjuvant CT and concomitant Mytomicin and 5-FU. This result could be a very good approach and low cost treatment for elderly patients.

Discussion

Quality of life

RT, as an alternative therapy to surgery, could preserve native bladder capacity. The most important symptom after RT is incontinence. Zietman et al. [54] performed urinary dynamic tests and quality of life study in long-term survivors, treated with CRT. Of them 75% had bladder with normal function. Contracted bladder was present only in 2% of pts. Zietman also showed that 54% of men had good erections and 60% were satisfied of their sex life.

Future directions

Through the use of combination therapy with simulators and image-guided RT, administration of radiation therapy it has become more focused [80].

Numerous techniques are being validated and their clinical application clinic seems to be set to grow over the years.

Recent evidence showed that the re-irradiation, using high-precision RT machines, can be used successfully in the treatment of brain metastases, tumors of head and neck, lung, abdominal and pelvic neoplasms, as salvage therapy [81].

Protons can deliver conformal RT, with low effects in organs at risk (OARs) of complications, mainly small and large intestine. Brachytherapy permits to deliver high dose to a small area with sparing of OARs. It should be considered in lesions small and limited. Brachytheraphy was originally made with RADIUM 226, now with Iridium 192 (low dose rate and high dose rate) [82-84].

Hyperthermia is able to improve local control and CR rate (Quadrimodal therapy). Hyperthermia enhances RT induced DNA damage. Important advances in RT are represented by intensity modulated radiotherapy, image guided-radiotherapy  and stereotactic RT [85].

Traslational approach

Most recently have been identified markers of response to therapy. Epidermal growth factor receptor (EGFR) positivity seems to be an unfavorable prognostic factor and correlate with DSS and OS in the intact bladder. Also Retinoblastoma protein (Rb) and bcl-2 expression are independent correlates with RT response in muscle infiltrative bladder cancer (MIBC). Also p53 expression and level of apoptosis correlates with treatment response.

There are strongest predictive novel markers for outcome in patients receiving cystectomy or CCRT: patients with tat-interactive protein 60 expression have a significantly longer DSS after cystectomy and patients with expression of meiotic recombination 11 homolog have a better prognosis and a longer DSS after CCRT. [86-87].

Progress goes in the direction of 3D conformal RT combined with CT scans type big bore and novel imaging fusion (Single Photon Emission Computed Tomography, Positron Emission Tomography).

Conclusions

There is a new renaissance of RT in bladder cancer, mainly in conservative approach. RT not necessarily tries to replace surgery, but RT is a good alternative in patients contrary to urinary diversion and in old peoples.

Competing interests

Authors declare no conflict of interest.

Acknowledgements

Each author had participated in the work and is responsible for the content.

All authors have interpreted the data. The manuscript was written by Parisi Salvatore and Guglielmi Giuseppe, and all authors have approved the final manuscript.

References

References

1.American Cancer Society: Cancer Facts and Figures (2014) Atlanta, Ga: American Cancer Society, 2014.

2.Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer, 2012.

3.Data were provided by the Office for National Statistics on request, 2013.

4.Marsit CJ, Koestler DC, Christensen BC, Karagas MR, Houseman EA et al. DNA methylation array analysis identifies profiles of blood-derived DNA methylation associated with bladder cancer. J Clin Oncol. 2011, 29(9):1133-1139.

5.Cooksley CD, Avritscher EB, Grossman HB, Sabichi AL, Dinney CP et al. Clinical model of cost of bladder cancer in the elderly. Urology. 2008, 71(3): 519-525.

6.Fedeli U, Fedewa SA, Ward EM. Treatment of muscle invasive bladder cancer: evidence from the National Cancer Database, 2003 to 2007. J Urol. 2011, 185(1):72-78.

7.Froehner M, Brausi MA, Herr HW, Muto G, Studer UE. Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol. 2009, 56(3):443-454.

8.James ND, Hussain SA, Hall E, Jenkins P, Tremlett J et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012; 366(16):1477-1488.

9.Munro NP, Sundaram SK, Weston PM, Fairley L, HarrisonSC et al. A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire. Int J Radiat Oncol Biol Phys. 2010, 77(1):119-124.

10.Jahnson S, Damm O, Hellsten S, Holmäng S, Liedberg F et al. A population-based study of patterns of care for muscle-invasive bladder cancer in Sweden. Scand J Urol Nephrol. 2009, 43(4): 271-276.

11.Con and Ang Radiation Oncology Edition VIII Mosby 2003, page 584.

12.Tonoli S, Bertoni F, De Stefani A, Vitali E, De Tomasi D et al. Radical radiotherapy for bladder cancer: retrospective analysis of a series of 459 patients treated in an Italian institution. Clin Oncol (R Coll Radiol). 2006, 18(1): 52–59.

13.Langsenlehner T, Döller C, Quehenberger F, Stranzl-Lawatsch H, Langsenlehner U et al. Treatment results of radiation therapy for muscle-invasive bladder cancer. Strahlenther Onkol. 2010, 186(4): 203-209.

14.Sengelov L, Von der Maase H. Radiotherapy in bladder cancer. Radiother Oncol 1999, 52(1): 1–14.

15.Goffinet DR, Schneider MJ, Glatstein EJ, Ludwig H, Ray GR et al. Bladder cancer: results of radiation therapy in 384 patients. Radiology. 1975,117(1): 149-153.

16.Yu WS, Sagerman RH, Chung CT, Dalal PS, King GA. Bladder carcinoma. Experience with radical and preoperative radiotherapy in 421 patients. Cancer. 1985, 56(6):1293-1299.

17.Goodman GB, Hislop TG, Elwood JM, Balfour J. Conservation of bladder function in patients with invasive bladder cancer treated by definitive irradiation and selective cystectomy. Int J Radiat Oncol Biol Phys. 1981, 7(5): 569-573.

18.Duncan W, Quilty PM. The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. Radiother Oncol. 1986, 7(4): 299-310.

19.Blandy JP, Jenkins BJ, Fowler CG, Caulfield M, Badenoch DF et al. Radical radiotherapy and salvage cystectomy for T2/3 cancer of the bladder. Prog Clin Biol Res. 1988, 260:447-451.

20.Jenkins BJ, Caulfield MJ, Fowler CG, Badenoch DF, Tiptaft RC et al. Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer. Br J Urol. 1988, 62(4):343-346.

21.Gospodarowicz MK, Rider WD, Keen CW, Connolly JG, Jewett MA et al. Bladder cancer: long-term follow-up results of patients treated with radical radiation. Clin Oncol (R Coll Radiol).1991, 3(3):155-161.

22.Jahnson S, Pedersen J, Westman G. Bladder carcinoma--a 20-year review of radical irradiation therapy. Radiother Oncol. 1991, 22(2):111-117.

23.Davidson SE, Symonds RP, Snee MP, Upadhyay S, Habeshaw T et al. Assessment of factors influencing the outcome of radiotherapy for bladder cancer. Br J Urol. 1990, 66(3):288-293.

24.Greven KM, Solin LJ, Hanks GE. Prognostic factors in patients with bladder carcinoma treated with definitive irradiation. Cancer. 1990, 65(4):908-912.

25.Smaaland R, Akslen LA, Tønder B, Mehus A, Lote K et al. Radical radiation treatment of invasive and locally advanced bladder carcinoma in elderly patients. Br J Urol. 1991, 67(1):61-69.

26.Fosså SD, Waehre H, Aass N, Jacobsen AB, Olsen DR et al. Bladder cancer definitive radiation therapy of muscle-invasive bladder cancer. A retrospective analysis of 317 patients. Cancer. 1993, 72(10):3036-3043.

27.Vale JA, A’Hern RP, Liu K, Hendry WF, Whitfield HN et al. Predicting the outcome of radical radiotherapy for invasive bladder cancer. Eur Urol. 1993, 24(1):48-51.

28.Pollack A, Zagars GK, Dinney CP, Swanson DA, von Eschenbach AC et al. Preoperative radiotherapy for muscle-invasive bladder carcinoma. Long-term follow up and prognostic factors for 338 patients. Cancer. 1994, 74 (10): 2819–2827.

29.Moonen L, vd Voet H, de Nijs R, Horenblas S, Hart AA et al. Muscle-invasive bladder cancer treated with external beam radiation: influence of total dose, overall treatment time, and treatment interruption on local control. Int J Radiat Oncol Biol Phys. 1998, 42(3):525-530.

30.Langsenlehner T, Döller C, Quehenberger F, Stranzl-Lawatsch H, Langsenlehner U et al. Treatment results of radiation therapy for muscle-invasive bladder cancer. Strahlenther Onkol. 2010, 186(4):203-209.

31.Bloom HJG, Hendry WF, Wallace DM, Skeet RG. Treatment of T3 bladder cancer: controlled trial of preoperative radiotherapy and radical cystectomy and radical radiotherapy. Br J Urol. 1982, 54(2):136–151.

32.Cole CJ, Pollack A, Zagars GK, Dinney CP, Swanson DA et al. Local control of muscle invasive bladder cancer: preoperative radiotherapy and cystectomy versus cystectomy alone. Int J Radiat Oncol Biol Phys. 1995, 32(2):331–340.

33.Huncharek M, Muscat J, Geschwind JF. Planned preoperative radiation therapy in muscle invasive bladder cancer; results of a metaanalysis. Anticancer Res. 1998, 18(3B):1931–1934.

34.Smith Jr JA, Crawford ED, Paradelo JC, Blumenstein B, Herschman BR et al. Treatment of advanced bladder cancer with combined preoperative irradiation and radical cystectomy versus radical cystectomy alone: a phase three intergroup study. J Urol. 1997, 157(3): 805–808.

35.Malmstrom PU, Rintala E, Wahlqvist R, Hellström P, Hellsten S et al. Five-years follow up of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group. J Urol 1996, 155(6):1903–1906.

36. Coppin CM, Gospodarowicz MK, James K, Tannock IF, Zee B et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trial Group. J Clin Oncol. 1996, 14(11):2901–2907.

37.Spera JA, Whittington R, Littman P, Solin LJ, Wein AJ. A comparison of preoperative radiotherapy regimens for bladder carcinoma: the University of Pennsylvania experience. Cancer 1988, 61(2):255–262.

38.Reisinger SA, Mohiuddin M, Mulholland SG. Combined preand postoperative adjuvant radiation therapy for bladder cancer- a ten year experience. Int J Radiat Oncol Biol Phys 1992, 24(3):463–468.

39.Zaghlou MS, Awwad HK, Akoush HH, Omar S, Soliman O et al. Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control. Int J Radiat Oncol Biol Phys 1992, 23(3):511–517.

40.Zapatero A, Martin de Vidales C, Marin A, Cerezo L, Arellano R et al. Invasive bladder cancer: a single-institution experience with bladder-sparing approach. 2000, Int J Cancer. 90(5):287– 294.

41.Skinner DG, Tift JP, Kaufman JJ. High dose, short course preoperative radiation therapy and immediate single stage radical cystectomy with pelvic node dissection in the management of bladder cancer. J Urol 1982, 127(4):671–674.

42.Zaghlou MS. Radiation as adjunctive therapy to cystectomy for bladder cancer: is there a difference for bilharzial association? Int J Radiat Oncol Biol Phys 1994, 28(3):783.

43.Kopelson G, Heaney JA. Postoperative radiation therapy for muscle-invading bladder carcinoma. J Surg Oncol 1983, 23(4):263–268.

44.Kamat AM. Commentary on “Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience.” Yafi FA, Aprikian AG, Fradet Y et al. Department of Surgery (Urology), McGill University, Quebec, Canada:BJU Int2012,110(9):1317-23 [Epub 2012 Apr 13]. Urol Oncol. 2013, 31(5):717-718.

45.Baumann BC, Guzzo TJ, He J, Vaughn DJ, Keefe SM et al. Bladder cancer patterns of pelvic failure: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys. 2013, 85(2): 363-369.

46.International Collaboration of Trialists. Neoadiuvant cisplatin, methotrexate and vinblastine for muscle invasive bladder cancer: a randomized controlled trial. Lancet. 1999, 354(9178):533-540.

47.Advanced Bladder Cancer Meta-analysys Collaboration (ABC). Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysys. Lancet. 2003, 361(9373):1927–1934.

48.Tester W, Porter A, Asbell S, Coughlin C, Heaney J et al. Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. Int J Radiat Oncol Biol Phys. 1993, 25(5):783–790.

49.Kaufman DS, Winter KA, Shipley WU, Heney NM, Chetner MP et al. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist. 2000, 5(6):471– 476.

50.Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL et al. RTOG 97-06: initial report of a fase I-II trial of selective bladder conservation using TURBT, twice daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003, 57(3):665–672.

51.Tester W, Caplan R, Heaney J, Venner P, Whittington R et al. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group Phase II trial 8802. J Clin Oncol. 1996, 14(1):119–126.

52.Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998, 16(11):3576–3583.

53.Kachnic LA, Kaufman DS, Heney NM, Althausen AF, Griffin PP et al. Bladder preservation by combined modality therapy for invasive bladder cancer. J Clin Oncol. 1997, 15(3):1022– 1029.

54.Zietman AL, Shipley WU, Kaufman DS, Zehr EM, Heney NM et al. A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-FU and twice daily radiation followed by selective bladder preservation in operable patients with muscle-invading bladder cancer. J Urol. 1998,160(5):1673– 1677.

55.. Housset M, Dufour B, Maulard-Durdux C. Concomitant fluorouracil (5-FU)-cisplatin (CDDP) and bifractionated split course radiation therapy (BSCRT) for invasive bladder cancer. Proc Am Soc Clin Oncol. 1997,16:319a.

56.Rödel C, Grabenbauer GG, Kuhn R, Thomas Papadopoulos, Jürgen Dunst et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol. 2002, 20(14):3061–3071.

57.Russell KJ, oileau MA, Higano C, Collins C, Russell AH et al. Combined 5- fluorouracil and irradiation for transitional cell carcinomaof the urinary bladder. Int J Radiat Oncol Biol Phys. 1990, 19(3):693–699.

58.Rotman M, Aziz H, Porrazzo M, Choi KN, Silverstein M et al. Treatment of advanced transitional cell carcinoma of the urinary bladder with irradiation and concomitant 5-fluorouracil infusion. Int J Radiat Oncol Biol Phys. 1990,18(5):1131–1137.

59.Orsatti M, Curotto A, Canobbio L, Guarneri D, Scarpati D et al. Alternating chemo-radiotherapy in bladder cancer: a conservative approach. Int J Radiat Oncol Biol Phys 1995, 33(1):173–178.

60.Given RW, Parsons JT, McCarley D, Wajsman Z. Bladder-sparing multimodality treatment of muscle invasive bladder cancer: a five-year follow up. Urology. 1995, 46(4):499–504.

61.Varveris H, Delakas D, Anezinis P, Haldeopoulos D, Mazonakis M et al. Concurrent platinum and docetaxel chemotherapy and external radical radiotherapy in patients with invasive transitional cell bladder carcinoma: A preliminary report of tolerance and local control. Anticancer Res. 1997, 17(6D):4771–4780.

62.Fellin G, Graffer U, Bolner A, Ambrosini G, Caffo O et al. Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single- institution phase II study. Br J Urol 1997,80(1):44–49.

63.Sauer R, Birkenhake S, Kühn R, Wittekind C, Schrott KM et al. Efficacy of radiochemotherapy with platin derivatives compared to alone in organ-sparing treatment of bladder cancer. Int J Radiat Oncol Biol Phys 1998, 40(1):121–127.

64.Cervek J, Cufer T, Zakotnik B, Kragelj B, Borstnar S et al. Invasive bladder cancer: our experience with bladder sparing approach. Int J Radiat Oncol Biol Phys. 1998, 41(2):273–278.

65.Arias F, Domínguez MA, Martínez E, Illarramendi JJ, Miquelez S et al. Chemoradiotherapy for muscle invading bladder carcinoma:Final report of a single institutional organ sparing program. Int J Radiat Oncol Biol Phys. 2000, 47(2):373–378.

66.Shipley WU, Kaufman DS, Zehr E, Heney NM, Lane SC et al. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology. 2002, 60(1):62–67.

67.Caffo O, Fellin G, Graffer U, Valduga F, Bolner A et al. Phase I study of Gemcitabine and radiotherapy plus Cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer. Int J Radiat Oncol Biol Phys. 2003, 57(5):1310–1316.

68.Chen WC, Liaw CC, Chuang CK, Chen MF, Chen CS et al. Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2003, 56(3):726–733.

69.Peyromaure M, Slama J, Beuzeboc P, Ponvert D, Debré B et al. Concurrent chemoradiotherapy for clinical stage T2 bladder cancer: Report of a single institution. Urology. 2004, 63(1): 73–77.

70.Danesi DT, Arcangeli G, Cruciani E, Altavista P, Mecozzi A et al. Conservative treatment of invasive bladder carcinoma by transurethral resection, protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy: Long term results. Cancer. 2004, 101(11):2540–2548.

71.Hussain SA, Stocken DD, Peake DR, Glaholm JG, Zarkar A et al. Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer. Br J Cancer. 2004, 90(11):2106–2211.

72.Kragelj B, Zaletel-Kragelj L, Sedmak B, Cufer T, Cervek J. Phase II study of radiochemotherapy with vinblastine in invasive bladder cancer. Radiother Oncol. 2005, 75(1): 44–47.

73.Dunst J, Diestelhorst A, Kühn R, Müller AC, Scholz HJ et al. Organ sparing treatment in muscle-invasive bladder cancer. Strahlenther Onkol. 2005,181(10):632–637.

74.Rodel C, Weiss C, Sauer R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol. 2006, 24(35):5536–5544.

75.Hoskin PJ, Rojas AM, Saunders MI, Bentzen SM, Motohashi KJ et al. Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial. Radiother Oncol. 2009, 91(1):120-125.

76.Troiano M, Corsa P, Raguso A, Cossa S, Piombino M et al. Radiation therapy in urinary cancer: state of the art and perspective. Radiol Med. 2009, 114(1):70-82.

77.Pos FJ, Hart G, Schneider C, Sminia P. Radical radiotherapy for invasive bladder cancer: what dose and fractionation schedule to choose? Int J Radiat Oncol Biol Phys. 2006, 64(4):1168–1173.

78.Stuschke M, Thames HD. Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys. 1997, 37(2):259–267.

79.Horwich A, Dearnaley D, Huddart R, Graham J, Bessell E et al. A randomized trial of accelerated radiotherapy for localized invasive bladder cancer. Radiother Oncol. 2005,75(1): 34–43.

80.Cheung R. Target volumes, image fusion and contouring in modern radiotherapy treatment planning. JJ Rad Oncol 2014, 1(2): 1-5.

81.Cheung R. Using a Robotic stereotactic radiation treatment system for re-irradiation may be safe and effective. JJ Rad Oncol 2014, 1(2): 1-3.

82.Kob D, Arndt J, Kriester A, Schwenk M, Kloetzer KH. Results of percutaneous radiotherapy of bladder cancer using 1 and 2 series of irradiation. Strahlenther Onkol. 1985, 161(11):673– 677.

83.Koning CC, Blank LE, Koedooder C, van Os RM, van de Kar M et al. Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1- pT3 bladder tumors. Ann Oncol. 2012, 23(11):2948-2953.

84.Aluwini S, van Rooij PH, Kirkels WJ, Boormans JL, Kolkman- Deurloo IK et al. Bladder function preservation with brachytherapy, external beam radiation therapy, and limited surgery in bladder cancer patients: long-term results. Int J Radiat Oncol Biol Phys. 2014, 88(3):611-617.

85.Thariat J, Trimaud R, Angellier G, Caullery M, Amiel J et al. Innovative image-guided CyberKnife stereotactic radiotherapy for bladder cancer. J Radiol. 2010, 83(990):e118-121.

86.Choudhury A, Nelson LD, Teo MT, Chilka S, Bhattarai S et al. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010, 70(18):7017-7026.

87.Laurberg JR, Brems-Eskildsen AS, Nordentoft I, Fristrup N, Schepeler T et al. Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int. 2012, 110(11 Pt C):E1228-1236.

Cite this article: Giuseppe G. Bladder Cancer Treatment: Review of Literature. J J Rad Oncol. 2015, 2(2): 018.

Contact Us:
9600 GREAT HILLS
TRAIL # 150 W
AUSTIN, TEXAS
78759 ( TRAVIS COUNTY)
E-mail : info@jacobspublishers.com
Phone : 512-400-0398