The gold standard management of NMIBC is a TURBT, aiming to remove all visible lesions. Detailed guidance on best practice is provided by many bodies including the European Association of Urology (EAU) and American Urological Association (AUA) [6, 7]. Many studies have evaluated the benefits of using Photodynamic Diagnosis (PDD) during which either 5-aminolevulinic acid (ALA) or hexaminolevulinic acid (HAL) are instilled into the bladder before cystoscopy is performed using ultraviolet light. Results are mixed with some studies finding no improvement in recurrence rates [8, 9] and others reporting improvements [10–12]. Currently the use of PDD is not routinely included in treatment algorithms but is used in many centers [6].

Patients with Ta and T1 tumors can be divided into low-, intermediate-, and high-risk groups using the EORTC scoring system [13]. The factors included are number of tumors, size of tumors, prior recurrence rate, T category in TNM staging, presence of concurrent carcinoma in situ and tumor grade.

Stratification into low, intermediate, and high risks can be used to identify which patients may benefit most from maintenance treatments. Low-risk tumors may only require one immediate post-operative instillation of chemotherapy, whereas those with intermediate risk are recommended to receive a year of maintenance treatment. This can be with either intravesical Bacillus Calmette–Guerin (BCG) or chemotherapy. Patients with high-risk tumors are recommended to continue BCG instillations for up to 3 years.

This risk stratification also helps determine which surveillance schedule is recommended, although no clear consensus exists about the precise follow-up schedule. The EAU guidelines suggest patients with low-risk tumors undergo cystoscopy at 3 months, 9 months and then annually for 5 years. Patients with high-risk tumors should undergo both cystoscopy and urine cytology at 3 months, then 3 monthly for 2 years, 6 monthly for 5 years, and annual cystoscopy thereafter. Patients with intermediate-risk tumors should have a surveillance schedule in between that for low- and high-risk patients [6].

Evidence for the use of both immunotherapy and chemotherapy exists in NMIBC.

Intravesical instillations using BCG have been shown to reduce recurrence rates compared to TURBT alone [14] and compared to intravesical chemotherapy [15, 16]. No clear guidance for dosing, timing, and durations are published, although there is consensus that it should be given on a maintenance schedule and not as a single post-operative instillation, unlike chemotherapy which can in some cases be given as a single treatment [16, 17]. The AUA advocates the use of the SWOG regimen, a 6-week induction course of BCG followed by a 3-week maintenance course at 3, 6, 12, 18, 24, 30, and 36 months [7].

Adjuvant treatment with intravesical chemotherapy using mitomycin C (MMC), epirubicin, thiopeta, and doxorubicin are all used. However, as a result of limited availability of the other drugs, MMC is the most widely used. Sylvester et al. performed a meta-analysis of a single immediate post-operative instillation, including 7 randomized trials using MMC, thiopeta, and epirubicin, with recurrence data on 1476 patients and showed a significant decrease in the risk of recurrence with an odds ratio (OR) 0.61(p < 0.0001) [18]. The benefits of further instillations remain unclear. However, Sylvester et al. also performed a meta-analysis examining this and concluded that they may be beneficial in higher risk patients [19]. However, no clear guidance on the exact dosing, timing, and duration of ongoing instillations has been published.

In some cases of NMIBC radical cystectomy is indicated. These include all patients who have or develop BCG refractory disease. It should also be considered as a potential treatment in those with multiple, larger tumors, concurrent CIS, disease in the prostatic urethra, and micropapillary histology.

Radical cystectomy with lymph node dissection is the gold standard treatment for MIBC if the patient is fit for surgery. Lymph node dissection can be either standard (regional bilateral node dissection), extended (to aortic bifurcation), or super-extended (to inferior mesenteric artery). Extended lymph node dissection has been shown in a number of retrospective studies to be beneficial [20, 21], but currently no clear recommendation for its use exists, pending the results of randomized controlled trials [22].

Classically the 5-year survival rate, following radical cystectomy, is approximately 50 % [23] and so the benefits of adjuvant treatment have been investigated. Neoadjuvant chemotherapy, consisting of a cisplatin based regimen, has been shown to result in a 5 % improvement in overall survival in a number of meta-analyses for stage II and III disease [24–26]. The benefits of adjuvant chemotherapy, however, are not as well established, although a recent meta-analysis of nine randomized controlled trials revealed an overall survival benefit with a pooled hazard ratio of 0.77 (95 % confidence interval (CI) 0.59–0.99; p = 0.049). It is only currently recommended in high-risk patients who have not received neoadjuvant treatment [4].

This approach is appropriate if patients are not fit for radical surgery or express a personal preference for a bladder conserving approach. Treatment is a combination of TURBT, chemotherapy, and radiotherapy, with a tri-modal combination being the preferred treatment option. The addition of cisplatin based chemotherapy improves outcomes with both radical and adjuvant radiotherapy following TURBT [27]. Five-year survivals between 50 and 60 % have been demonstrated, making this a feasible approach for some patients [28, 29]. These patients must undergo vigorous follow-up and bladder surveillance, as by retaining their bladder they remain at risk of both recurrence and new bladder tumors.

Currently chemotherapy combinations, containing cisplatin, form the basis of first line treatment in advanced or metastatic disease. Both Gemcitabine and Cisplatin (GC) and Methotrexate, Vinblastine, Adriamycin, and Cisplatin (MVAC) have shown prolonged median survival rates of 13.8 months and 14.8 months [30, 31]. GC is less toxic than MVAC and is therefore usually the regimen of choice [30]. It is estimated that up to 50 % patients with advanced or metastatic disease are not fit to receive cisplatin therapy, due to a variety of factors including poor renal function and performance status [32]. It is common practice to replace cisplatin with carboplatin in this situation and to use it in combination with gemcitabine [33].

Patients progressing following first line chemotherapy have limited further treatment options. Vinflunine, a third generation vinca alkaloid, remains the only licensed treatment in the second line setting for MBC. However, despite phase III trial evidence [34] and the lack of other treatment options, vinflunine has not been widely adopted into clinical practice.

An alternate strategy if relapse or progression occurs greater than 6 months after first line chemotherapy is to rechallenge the patient with cisplatin based combination chemotherapy or enrolment in a clinical trial.

In recent years, a large number of cytotoxic and targeted therapies have been investigated in phase II and III clinical trials, although these studies have yet to result in any new licensed treatments. At present, however, immunotherapy is undergoing a renaissance in solid cancer treatment. In advanced bladder cancer, checkpoint inhibitors targeting programmed cell death (PD-1) and its primary ligand PD-L1 have demonstrated the most promising results in the last 30 years. Powles et al. reported results of an extended phase I trial of Atezolizumab (MPDL3280A) a PD-L-1 inhibitor which demonstrated significant activity in advanced bladder cancer. They showed it is the most active against tumors with PD-L1 positive tumor infiltrating immune cells with objective response rates 43 % (13/30 patients CI 26–63 %), but still demonstrated objective response rates of around 11 % (4/35 CI 4–26 %) in PD-L1 negative tumors [35]. Similarly promising results were reported by Plimack et al. using Pembrolizumab, an anti-PD1 antibody [36]. This led to the US FDA granting this class of agent ‘breakthrough drug’ status in 2014 and later stage clinical trials are currently ongoing.

Both surgery and radiotherapy are used as palliative treatments to treat localized symptoms such as frank hematuria or pain. Skeletal related events can also be minimized for patients with bone metastases using intravenous bisphosphonates [37]. In the absence of multiple treatment options for patients with advanced or metastatic disease, best supportive care remains of great importance [38].