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Cicione et al. Mini-invasive Surg 2021;5:47  https://dx.doi.org/10.20517/2574-1225.2021.52  Page 5 of 11


 Table 2. Current guidelines on bladder preserving approaches for MIBC

 Association Patient selection criteria  Radiotherapy  Chemotherapy

 AUA  Highly selected patient   Halt the radiation at a dose of 40-45 Gy (approximately 2/3  Many prospective studies have reported high rates of local control (> 70%) in patients
 - Unfit for RC   of the total dose), repeat a cystoscopy with re-biopsy, and, if  selected for treatment on protocols that included cisplatin with or without 5-FU
 - Tumor resecable by TURB (< 3cm)   muscle invasive tumor still persists, recommend cystectomy
 - Absence of multifocal CIS and hydronefrosis  at that time
 and T3/T4 tumors
 - No histology variants
 - Well informed patient (40% subsequent
 RC)
 - Adequate bladder function
 - Follow-up
 ESMO  Option for patients seeking an alternative to   In case of bladder preservation with radiotherapy, combination with a radiosensitiser is always recommended to improve clinical outcomes, such as
 cystectomy and a palliative option for those   cisplatin, 5FU/MMC, carbogen/nicotinamide or gemcitabine
 who are medically unfit for surgery
 Ideal patient: early tumour stage (including
 high-risk T1 disease T2 < 5 cm), a visibly
 complete
 TURBT, absence of associated CIS and
 ureteral obstruction and adequate bladder
 capacity and function
 Lifelong surveillance is required to achieve
 optimal results
 EAU  Reasonable treatment option in well-selected  A standard radiation schedule includes EBRT to the bladder   Different chemotherapy regimens have been used, but most evidence exists for
 patients as well as patients with a   and limited pelvic LNs with an initial dose of 40 Gy, with a   cisplatin and mitomycin C plus 5-FU. In addition to these agents, other schedules have
 contraindication for surgery   boost to the whole bladder of 54 Gy and a further tumour   also been used, such as hypoxic cell sensitisation with nicotinamide, carbogen and
 High level of patient compliance is need,   boost, with a total dose of 64 Gy  gemcitabine, without clear preference for a specific radiosensitizer
 absence of carcinoma in situ, absence or
 presence of hydronephrosis, optimal
 debulking of initial cancer


 AUA: American Urological Association; ESMO: European Society for Medical Oncology; EAU: European Association of Urology; MIBC: muscle invasive bladder cancer; RC: radical cystectomy.



 Thus, 10%-30% of patients will require SRC after initial curative TMT with a mean 5-year DFS of 50% and 5-year OS rate of 33%-48%. However, those findings
 may be biased, hypothesizing that all patients requiring SRC were fit for surgery and studies included only patients with ≥ T2 N0M0 bladder cancer. In patients

 [23]
 undergoing RC at primary MIBC diagnosis, Stein et al.  showed an OS at 5 and 10 years of 78% and 56%, respectively, in the presence of organ confined
 disease with no lymph node involvement. Those rates were dramatically reduced in the presence of extravesical disease extension (5-year OS = 55%; 10-year
 OS = 27%) and lymph nodes involvement (5-year OS = 31%; 10-year OS = 23%).



 However, the rate of disease-free survival after SRC is higher than in the absence of treatment. Martini et al.  evaluated the natural history of MIBC in the
                                    [24]
 absence of treatment by analyzing 64 patients > 79 years old affected by T2-T4 N0 high-grade bladder cancer who did not receive any treatment. They found a
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