Bladder cancer is the sixth most prevalent cancer in the United States1. As of 2023, 82,290 new diagnoses of bladder cancer (62,420 in men and 19,870 in women) were documented, as well as 16,710 deaths.2 The median age at diagnosis of bladder cancer is 73 years, and approximately 1 in 28 individuals will be diagnosed with bladder cancer during their lifetime.2 Early detection of bladder cancer can be challenging because many individuals do not present with any symptoms. The most common – and sometimes only – symptom of bladder cancer is hematuria, or blood in the urine. Other, less common symptoms can include increased frequency of urination, urinary tract infection (UTI), and upper urinary tract infection.
Bladder cancers predominantly emerge as urothelial carcinomas with papillary tumor morphology. Lesions can be divided into 2 broad categories: non-muscle-invasive bladder cancer (NMIBC), which account for 75% of bladder cancers, and muscle-invasive bladder cancer (MIBC), which account for 25% of total bladder cancer cases. Although patients with NMIBCs have an optimistic 5-year prognosis, those with MIBCs usually have less-favorable outcomes.3 Early detection and appropriate treatment by tumor staging are essential for effective management and remission.
Staging of Bladder Cancer
Oncology treatment guidelines are highly dependent on pathologic stage and severity of illness. For this reason, it is important to clearly identify the staging criteria. Tumors are described based on their size and local spread (T), whether they have invaded the surrounding lymph nodes (N), and whether they have metastasized (M), at which time the cancer has spread to organs far from the original tumor.4
Following the letters, a number is used to denote severity, with higher numbers reflecting greater severity. This is with the exception of NMIBCs or stage 0 tumors, for which the tumors have descriptive identifiers.
Stage 0 (0a and 0is)
- All NMIBC tumors are stage 0
- Stage 0a includes papillary carcinomas
- Grading for stage 0a is Ta, N0, M0
- Stage 0is denotes flat carcinomas in situ (CIS)
- Grading for 0is is Tis, N0, M0
Stage I
- Tumor has started to grow into the connective tissue but is still well contained
- Grading is T1, N0, M0
Stage II
- Tumor has spread into the muscle wall of the bladder but has not passed it
- Grading for tumor that has spread to the inner muscle wall is T2a, N0, M0
- Grading for tumor that has spread to the outer muscle wall is T2b, N0, M0
Stage IIIA
- Tumors that have spread and have either passed through the muscle of the bladder to surrounding organs but have not spread into the lymph nodes or have not spread past the bladder muscle and have spread into 1 lymph node
- Staging can be T(3a, 3b, or 4a), N0, M0
- If 1 lymph node has cancer, staging can be T1-4a, N1, M0
Stage IIIB
- Tumors that have or have not spread past the muscle of the bladder to the surrounding organs and have spread to at least 2 lymph nodes
- Staging can be T1-4a, N2 or N3, M0
Stage IVA
- Tumors that have spread to the abdominal wall but may or may not have spread to any lymph nodes and have not metastasized
- Staging for these tumors can be T4b, N0-3, M0
- Stage IVA can also be tumors that have not spread past the bladder or to nearby lymph nodes but have metastasized to distant lymph nodes
- Staging for these tumors can be T1-4b, N0-3, M1a
Stage IVB
- Stage IVB tumors can be at any stage of spreading to nearby organs and lymph nodes but must have spread to at least 1 distant organ
- Staging is T1-4b, N0-3, M1b
Bladder Cancer Treatment Types
Following diagnostic evaluation (computed tomography [CT] or magnetic resonance imaging [MRI]), all patients with suspected NMIBC are advised to undergo transurethral resection of bladder tumor (TURBT), which is a surgical procedure that removes as much of the lesion as possible and to obtain a pathology specimen for tumor staging.
Prior to and following this procedure, a range of pharmacotherapeutic treatments are recommended based on stage of illness. Broadly, these treatments fall into 3 categories: chemotherapy, immunotherapy, and targeted therapy. Treatments can be delivered systemically (ie, via intravenous infusion) or through intravesical instillation, which are infusions delivered to the bladder via urethral catheter.5,6
Chemotherapy
Chemotherapeutic drugs damage DNA or impair DNA synthesis, forcing fast-growing cells to enter into apoptosis, or programmed cell death.
The following is a listing of chemotherapeutic agents approved by the US Food and Drug Administration for use in bladder cancer:
- Cisplatin
- Doxorubicin hydrochloride
- Fluorouracil
- Gemcitabine
- Mitomycin
- Thiotepa
- Valrubicin
Immunotherapy
Immunotherapies are a broad class of agents that generally work by activating the immune system to destroy cancerous cells. In bladder cancer, these include monoclonal antibody treatments, antibody-drug conjugates, and live-attenuated bacterial infusions. Monoclonal antibody treatments such as avelumab, nivolumab, and pembrolizumab work by blocking the activity of programmed death-1/programmed death ligand-1 (PD-1/PD-L1), a molecular pathway that shields cancer cells from the immune system. Antibody-drug conjugates (enfortumab vedotin-ejfy and scituzumab govitecan-hziy) are monoclonal antibodies that are covalently attached to a chemotherapy drug.
The following is a listing of FDA-approved immunotherapies for use in bladder cancer:
- Avelumab
- Bacillus Calmette-Guérin (BCG)
- Enfortumab vedotin-ejfy
- Nivolumab
- Pembrolizumab
- Sacituzumab govitecan-hziy
Targeted Therapy
Targeted therapies are designed to block specific genetic or molecular pathways that are disrupted in cancer cells. Examples include gene therapies and kinase inhibitors.
The following is a listing of FDA-approved targeted therapies for use in bladder cancer:
- Erdafitinib
- Nadofaragene firadenovec-vncg
Combination Therapies
As the name suggests, combination therapies combine multiple FDA-approved pharmacotherapies to optimize treatment of a disease. This is most frequently recommended as systemic chemotherapy during late-stage disease.
The following is a listing of FDA-approved, recommended combination therapies for bladder cancer:
- Gemcitabine-cisplatin
- Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC)
- High-dose MVAC
- Pembrolizumab with enfortumab
When and How To Use Different Treatments for Bladder Cancer
Different treatments are recommended based on stage of disease, size of lesion, and responsiveness to previous treatment.
The following tables review dosage, administration, treatment duration, and recommended use based on stage of disease for each of the 3 treatment categories.
Table 1. Management Guidelines for Chemotherapies for Bladder Cancer
| Drug | Proprietary Name(s) | Dosage | Administration | Treatment Duration | Recommended Use (Stage) |
| Cisplatin | 50 mg/m2 to 70 mg/m2 every 3 to 4 wk | IV infusion over 6 h | 6 wk | Advanced disease, stages II and III prior to surgery, stages IVa and IVb | |
| Doxorubicin hydrochloride | Adriamycin | 60 mg/m2 to 75 mg/m2 every 21 d | IV infusion | 3-6 cycles | Advanced disease, stages IVa and IVb |
| Fluorouracil* | Not indicated | IV infusion | Not indicated | Advanced disease, stage IVb, palliative care | |
| Gemcitabine | Gemzar | 500 to 3600 mg/m2 | Intravesical instillation | 6 wk | Non-advanced, stages 0 and I |
| Mitomycin | Jelmyto | 4 mg/mL every 6 wk | Intravesical instillation | Up to 11 additional treatments | Non-advanced, stages 0 and I |
| Thiotepa* | Tepadina | 60 mg in 30 to 60 mL of NaCl | Injection to bladder via urethral catheter | Not indicated | Non-advanced, stage 0 |
| Valrubicin | Valstar | 800 mg once a wk | Intravesical instillation | 6 wk | Non-advanced, stage 0, refractory CIS |
IV = intravenous; CIS = carcinoma in situ; NaCl = sodium chloride.
*Not recommended in any setting by NCCN.
From FDA-approved prescribing information.7-12
Table 2. Management Guidelines for Immunotherapies for Bladder Cancer
| Drug | Proprietary Name(s) | Dose | Administration | Treatment Duration | Recommended Use (Stage) |
| Avelumab | Bavencio | 800 mg every 2 wk | Intravenous infusion over 60 min | Until disease advances or toxicity becomes intolerable | Advanced disease, stage Ivb |
| BCG | 1 vial (50 mL total volume) | Intravesical instillation (held in bladder for 2 h prior to urination) | 6-wk course followed by maintenance therapy for 3 wk at months 3, 6, 12, 18, 24, 30, and 36 | Non-advanced, stages 0 and I | |
| Enfortumab vedotin-ejfy | Padcev | 1.25 mg/kg (maximum of 125 mg) on days 1,8, and 15 of 28-d treatment cycle | Intravenous infusion over 30 min | Until disease advances or toxicity becomes intolerable | Advanced disease, stage Ivb |
| Nivolumab | Opdivo | 240 mg every 2 wk or 480 mg every 4 wk | Intravenous infusion over 30 min | Until disease advances or toxicity becomes intolerable for up to 1 y | Advanced disease, stages II and II postsurgery, stage Ivb |
| Pembrolizumab | Keytruda | 200 mg every 3 wk or 400 mg every 6 wk | Intravenous infusion over 30 min | Until disease advances or toxicity becomes intolerable | Advanced disease, stage IVb, and recurrent bladder cancer |
| Sacituzumab govitecan-hziy | Trodelvy | 10 mg/kg weekly on days 1 and 8 of 21-d treatment cycle | Intravenous infusion | Until disease advances or toxicity becomes intolerable | Advanced disease, stage IV |
BCG = Bacillus Calmette-Guérin; IV = intravenous.
From FDA-approved prescribing information.13-18
Table 3. Management Guidelines for Targeted Therapies for Bladder Cancer
| Drug | Proprietary Name(s) | Dose | Administration | Treatment Duration | Recommended Use (Stage) |
| Erdafitinib | Balversa | 8 mg once daily; can be increased to 9 mg at 3 wk if phosphate levels are acceptable | Tablets taken orally | Indefinitely if tolerated | Advanced disease; used in individuals with specific mutations in FGFR2 or FGFR3 |
| Nadofaragene firadenovec-vncg | Adstiladrin; Instilidrin | 75 mL at a concentration of 3 x 1011 viral particles/mL once every 3 mo | Intravesical instillation over 1 h | Up to 1 y | Non-advanced disease but high-risk, BCG-unresponsive CIS |
BCG = Bacillus Calmette-Guérin; CIS = carcinoma in situ.
From FDA-approved prescribing information.19,20
Table 4. Management Guidelines for Combination Therapies for Bladder Cancer
| Drug Combination | Dose | Treatment Duration | Recommended Use (Stage) |
| Gemcitabine-cisplatin | 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of 28-d cycle and 100 mg/m2 of cisplatin on day 1 | 4 cycles | Advanced disease: stage IIIB, stage IVA, stage IVB, recurrent bladder cancer |
| MVAC | 28-d cycle; 30 mg/m2 of methotrexate on days 1, 15, and 22;3 mg/m2 of vinblastine on days 2, 15, and 22;30 mg/m2 of doxorubicin on day 2; 70 mg/m2 of cisplatin on day 2 | 6 cycles | Advanced disease: stage IIIB, stage IVA, stage IVB, recurrent bladder cancer |
| High-dose MVAC/ DDMVAC | 14-day cycle; 30 mg/m2 of methotrexate on day 1;3 mg/m2 of vinblastine on day 2;30 mg/m2 of doxorubicin on day 2; 70 mg/m2 of cisplatin on day 2 | 3-6 cycles | Advanced disease: stage IIIB, stage IVA, stage IVB, recurrent bladder cancer |
| Pembrolizumab with enfortumab | 200 mg every 3 wk or 400 mg every 6 wk of pembrolizumab; 1.25 mg/kg of enfortumab on days 1 and 8 of a 21-d cycle; enfortumab given first if both agents are administered on the same day | Until disease advances or toxicity becomes intolerable for up to 24 mo | Advanced disease: stages II and II postsurgery, stage IVb |
MVAC = methotrexate, vinblastine, doxorubicin, and cisplatin; DDMVAC = double-dose MVAC.
From FDA-approved prescribing information.17,18
Monitoring Side Effects of Bladder Cancer Treatment
Adverse effects from pharmacotherapeutic treatments are a primary reason to modify or discontinue a treatment regimen. Generally, chemotherapy can cause toxicity to unintended organs. Chemotherapy damages fast-growing cells; while cancerous cells are rapidly growing and dividing, healthy cell types such as those in hair, skin, and the gastrointestinal tract also grow quickly. Thus, these cells are also often susceptible to chemotherapy-induced cell death.
Any medication that enters the bloodstream will have the potential to impair the liver and kidneys, as these organs remove harmful metabolites from the bloodstream.
Although locally contained, intravesical instillation of any treatment through a urethral catheter can cause the patient to experience discomfort and irritation.
The following tables review common side effects, side effects that require treatment discontinuation or modification, and drug-drug interactions associated with treatments for bladder cancer, as well as clinical considerations for special populations.
Table 5. Side Effect Profiles for Chemotherapies for Bladder Cancer
| Drug | Most Common Adverse Events | Side Effects Requiring Treatment Discontinuation or Modification | Drug-Drug Interactions | Special Populations |
| Cisplatin | Renal toxicity, ototoxicity, myelosuppression | Nephrotoxicity, neuropathy, ototoxicity | Anticonvulsants (less therapeutic), pyridoxine with altretamine | Lactating patients should not breastfeed; not recommended during pregnancy; increased likelihood of renal failure in elderly patients |
| Doxorubicin hydrochloride | Cardiomyopathy and arrhythmias, secondary malignancies, extravasation and tissue necrosis, severe myelosuppression, tumor lysis syndrome, radiation sensitization and radiation recall | Cardiomyopathy, hepatic impairment | Inhibitors and inducers of CYP3A4, CYP2D6, and P-gp; paclitaxel; trastuzumab; dexrazoxane; 6-mercaptopurine | Risk to fetus; lactation is not recommended; as infertility is possible for both men and women, contraception is recommended for sexually active individuals; higher risk for pediatric population |
| Fluorouracil | Low DPD, cardiotoxicity, hyperammonemic encephalopathy, neurologic toxicity, diarrhea, hand-foot syndrome, myelosuppression, inflammation of the oral mucosa, increased risk of elevated INR with warfarin | Low DPD, cardiotoxicity, hyperammonemic encephalopathy, neurologic toxicity, diarrhea, hand-foot syndrome, myelosuppression, inflammation of the oral mucosa, increased risk of elevated INR with warfarin | Anticoagulants and CYP2C9 substrates | Risk to fetus; lactation is not recommended; as infertility is possible for both men and women, contraception is recommended for sexually active individuals; patients of childbearing potential should refrain from getting pregnant for 3 mo following treatment |
| Gemcitabine | Hematologic, pulmonary, renal, hepatic | Pulmonary toxicity, renal toxicity | None indicated | Embryotoxic; not recommended in pregnant or lactating patients |
| Mitomycin | Ureteric obstruction, flank discomfort, UTI, hematuria (blood in urine), abdominal discomfort, fatigue, renal dysfunction, nausea, dysuria (painful urination), vomiting | Ureteric obstruction (58%), bone marrow suppression | None indicated | Not recommended in pregnant patients; can cause fetal harm; lactating individuals should wait 1 wk following the last treatment to breastfeed |
| Thiotepa | Myelosuppression, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, neural toxicity, carcinogenicity | Anaphylaxis, nervous system toxicity | Cytochrome CYP3A inhibitors and inducers, cytochrome CYP2B6 substrates | Could cause harm to a fetus; lactation is not recommended during treatment; men should be advised to use contraception for at least 1 y after discontinuation of use; women should be advised to use contraception for at least 6 mo after discontinuation of use |
| Valrubicin | Urinary frequency, dysuria, urinary urgency, bladder spasm, hematuria, bladder pain, urinary incontinence | None indicated | None indicated | Could cause harm to fetus; lactating patients should not breastfeed during treatment and for 2 wk after discontinuation of use |
UTI = urinary tract infection; DPD = dipyrimidine dehydrogenase; INR = international normalized ratio; P-gp = P-glycoprotein.
From FDA-approved prescribing information.5-10
Table 6. Side Effect Profiles for Immunotherapies for Bladder Cancer
| Drug | Most Common Adverse Events | Side Effects Requiring Treatment Discontinuation or Modification | Drug-Drug Interactions | Special Populations |
| Avelumab | Severe and fatal immune-mediated reactions, infusion-related reactions, complications of allogeneic HSCT, major cardiovascular events | Immune-mediated reactions, infusion-related reactions, cardiovascular events | None indicated | Can cause harm to fetuses; approved for use in pediatric patients older than 12 y |
| BCG | Dysuria, urinary frequency, flu-like syndrome, hematuria, fever | Fever and acute febrile illness | Immunosuppressants; bone marrow depressants; radiation; antimicrobial therapy may interfere with efficacy | Not recommended for pregnant or lactating patients |
| Enfortumab vedotin-ejfy | Skin reactions, hyperglycemia, pneumonitis, peripheral neuropathy, ocular disorders, infusion site extravasation | Pneumonitis, peripheral neuropathy, hyperglycemia | Use of enfortumab in conjunction with dual P-gp and potent CYP3A4 inhibitors may result in increased exposure to MMAE | Not for use in patients with moderate or severe hepatic impairment; not advised for patients who are lactating; can cause harm to fetuses |
| Nivolumab | Fatigue, rash, musculoskeletal discomfort, skin itching, diarrhea, nausea, weakness, cough, labored breathing, constipation, reduced appetite, back pain, joint pain, upper respiratory tract infection, fever, headache, abdominal pain, vomiting, UTI | Immune-mediated reactions, infusion-related reactions | None indicated | Could cause harm to fetus; lactating patients should not breastfeed for at least 5 mo after discontinuation of use |
| Pembrolizumab | Fatigue, musculoskeletal discomfort, skin itching, rash, nausea, reduced appetite, hyperglycemia, anemia, lymphopenia, hypoalbuminemia, hyponatremia, elevated alkaline phosphatase and creatinine, hypophosphatemia, elevated liver enzymes, hyperkalemia, hypocalcemia | Immune-mediated reactions, infusion-related reactions | None indicated | Could cause harm to fetus; lactating patients should not breastfeed for at least 4 mo after discontinuation of use |
| Sacituzumab govitecan-hziy | Decreased leukocytes, neutrophils, lymphocytes, and hemoglobin; diarrhea; nausea; fatigue; hair loss; constipation; elevated glucose; decreased albumin; vomiting; reduced appetite; reduced creatinine clearance; elevated alkaline phosphatase; reduced magnesium, potassium, and sodium | Infusion-related reactions, neutropenia, nausea/vomiting, diarrhea | UGT1A1 inhibitors and inducers | Could cause harm to a fetus; lactating patients should not breastfeed for at least 1 month after discontinuation of use; men should be advised to use contraception for 3 months after discontinuation of use; women should be advised to use contraception for 6 months after discontinuation of use |
BCG = Bacillus Calmette-Guérin; HSCT = hematopoietic stem cell transplantation; AST = aspartate aminotransferase; MMAE = monomethyl auristatin E; P-gp = P-glycoprotein; UTI = urinary tract infection.
From FDA-approved prescribing information.11-16
Table 7. Side Effect Profiles for Targeted Therapies for Bladder Cancer
| Drug | Most Common Adverse Events (>20%) | Side Effects Requiring Treatment Discontinuation or Modification | Drug-Drug Interactions | Special Populations |
| Erdafitinib | Elevated phosphate, inflammation of the oral mucosa, fatigue, elevated creatinine, diarrhea, dry mouth, nail disorders, elevated liver enzymes, elevated alkaline phosphatase, reduced sodium, reduced appetite, reduced albumin, dysgeusia, reduced hemoglobin, dry skin, reduced magnesium, dry eye, hair loss, palmar-plantar erythrodysesthesia syndrome, constipation, reduced phosphate, abdominal discomfort, elevated calcium, nausea, musculoskeletal discomfort | Ocular disorders, hyperphosphatemia, soft tissue mineralization | Moderate CYP2C9 or strong CYP3A4 inhibitors, moderate or strong CYP2C9 and CYP3A4 inducers, agents that alter serum phosphate levels, CYP3A4 substrates, OCT2 substrates, P-gp substrates | Breastfeeding is not recommended; could cause harm to a fetus; men with female sexual partners should use appropriate contraception |
| Nadofaragene firadenovec-vncg | Increased glucose, discharge at instillation site, elevated triglycerides, fatigue, bladder spasms, urinary urgency, elevated creatinine, hematuria, reduced phosphate, chills, fever, painful urination | Bladder spasm; instillation site discharge, benign bladder neoplasm | UGT1A1 inhibitors or inducers | Avoid use in immunocompromised patients; pregnant patients should be advised on risk to fetus |
OCT2 = organic cation transporter 2; P-gp = P-glycoprotein.
From FDA-approved prescribing information.1,21
Guidelines for the Management of Bladder Cancer
Guidelines for the pharmacotherapeutic treatment of bladder cancer consider the following factors:
- Size of the tumor
- Whether the tumor has invaded the muscle
- What surrounding organs have been invaded
- Whether the cancer has spread to local lymph nodes
- Whether and the extent to which the tumor has metastasized
- Previous treatments (including surgery and radiation)
- Previous responsiveness to treatments
- Individual health history
Depending on the severity of disease, the goals for treatment may change. For NMIBC, the predominant objective is to prevent recurrence and cease illness advancement. For MIBC, goals are modified to increase the patient’s chance of recovery. Once the tumor has metastasized, treatment goals are more palliative to improve length and quality of life.1 In accordance with treatment recommendations established by the National Cancer Institute and the National Comprehensive Cancer Network, 1,3 the following recommendations are presented by stage of illness.
Bladder Cancer Stages 0 and I
All patients are recommended to undergo TURBT. Some may also choose to have a partial or full cystectomy, a surgical procedure to remove the bladder. Patients can receive intravesical chemotherapy during the surgical procedure. Options for intravesical chemotherapy during surgery are mitomycin and gemcitabine.
Following surgery, intravesical maintenance therapy with BCG may be recommended. If patients do not tolerate or respond well to BCG, they can receive intravesical chemotherapy with mitomycin and gemcitabine. In response to ongoing BCG shortages, vials of BCG can be divided into thirds; however, the lower dose is not as effective as the full dose. In this case, intravesical chemotherapy is also recommended.
Following TURBT, patients will be assessed for relative future risk. NMIBCs are categorized as low, intermediate, or high risk,1 with appropriate treatment guidelines based on that categorization.
Low Risk
- A single session of intravesical chemotherapy is recommended during TURBT
- Surveillance
Intermediate Risk
- Management with intravesical therapy is preferred
- BCG is the intravesical therapy of choice
- Intravesical mitomycin and gemcitabine are recommended when BCG is not tolerated or unavailable
High Risk
- If there are no very-high-risk features, BCG is preferred but cystectomy is an option
- If there are very-high-risk features, cystectomy is preferred but BCG is an option
- If patient is unresponsive to BCG, cystectomy is preferred but intravesical chemotherapy with gemcitabine or mitomycin can be given
- If patient is unresponsive to BCG and has CIS, intravesical valrubicin can be given
- If patient is unresponsive to BCG, has Tis, and does not undergo cystectomy (either by choice or eligibility), pembrolizumab is recommended
- If patient is unresponsive to BCG and has CIS or Ta/T1 tumor, intravesical nadofaragene firadenovec-vncg can be used
During stages 0 and I of bladder cancer, for any instance in which intravesical chemotherapy is used, gemcitabine is usually favored due to tolerability and cost.1
Bladder Cancer Stages II and III
During stages II and III of bladder cancer, radical cystectomy — surgery to remove the bladder and surrounding organs — is usually recommended. Radiation and systemic chemotherapy are also recommended at this time. Prior to surgery, chemotherapy with cisplatin is recommended. Postoperatively, adjuvant therapy or immunotherapy with nivolumab is recommended when there is a high risk of cancer recurrence. Adjuvant therapy refers to any systemic pharmacotherapeutic treatment administered postoperatively.
If patients do not undergo surgery, either by choice or because they are medically unable, radiation is recommended in combination with chemotherapy (such as cisplatin or fluorouracil).3
Stage II
- Combination systemic cisplatin chemotherapy followed by radical cystectomy and postoperative adjuvant treatment is the most recommended stage II bladder cancer treatment
- In select patients with no Tis and highly localized tumors, combination cisplatin chemotherapy followed by partial cystectomy and postoperative adjuvant treatment is recommended
- For patients who cannot receive cisplatin-based chemotherapy, cystectomy alone is recommended with postoperative adjuvant treatment
- Following any type of cystectomy, if no previous cisplatin-based therapy has been used, MVAC for 3 to 6 cycles is recommended
- Following any type of cystectomy, if the patient has received previous cisplatin-based therapy or is more concerned with delaying recurrence rather than curing disease, nivolumab is recommended
- Patients who choose radiation with chemotherapy and no surgery should receive systemic cisplatin and can subsequently receive intravesical or systemic chemotherapy if tumor persists1
Stage IIIA
- Combination systemic cisplatin chemotherapy followed by radical cystectomy and postoperative adjuvant treatment is the most recommended stage IIIA bladder cancer treatment
- For patients who cannot receive cisplatin-based chemotherapy, cystectomy alone is recommended with postoperative adjuvant treatment
- Following any type of cystectomy, if no previous cisplatin-based therapy has been used, MVAC for 3 to 6 cycles is recommended
- Following any type of cystectomy, if the patient has received previous cisplatin-based therapy or is more concerned with delaying recurrence rather than curing disease, nivolumab is recommended
- Patients who choose radiation with chemotherapy and no surgery should receive systemic cisplatin and can subsequently receive intravesical or systemic chemotherapy if tumor persists1
Stage IIIB
- Systemic chemotherapy with gemcitabine and cisplatin followed by avelumab for maintenance therapy is recommended
- If patients undergoing systemic chemotherapy are not eligible for cisplatin-containing therapies, gemcitabine and carboplatin are recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies, pembrolizumab is recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies and their tumors express PD-L1, atezolizumab is recommended
- If radiation is used in addition to systemic chemotherapy, cisplatin is recommended or low-dose gemcitabine is recommended if the patient is not eligible for cisplatin-containing therapies1
Stage IVA
At this advanced stage, systemic, combinatorial chemotherapies are recommended. MVAC; high-dose MVAC; and cisplatin, methotrexate, and vinblastine are all recommended for stage IVA bladder cancer. If the patient decides to undergo surgery, cisplatin is recommended prior to surgery. If the patient opts for radiation, cisplatin and fluorouracil should also be administered. Other surgical options available are for palliative care.3
- For M0 and M1a disease, systemic chemotherapy with gemcitabine and cisplatin followed by avelumab for maintenance therapy is recommended
- If patients undergoing systemic chemotherapy are not eligible for cisplatin-containing therapies, gemcitabine and carboplatin are recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies, pembrolizumab is recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies and their tumors express PD-L1, atezolizumab is recommended
- M0 disease can also be treated with radiation and cisplatin alone or low-dose gemcitabine if the patient is not eligible for cisplatin-containing therapies1
Stage IVB
At this advanced stage, systemic, combinatorial chemotherapies are recommended. MVAC; high-dose MVAC; and cisplatin, methotrexate, and vinblastine are all recommended for stage IVB bladder cancer, similar to the recommendation for stage IVA bladder cancer. Gemcitabine with cisplatin or carboplatin is also recommended for stage IVB bladder cancer. Immunotherapies such as avelumab, nivolumab, or pembrolizumab can be used at this time. Other surgical and radiation options are available for palliative care.3
- For metastatic, M1b disease, systemic chemotherapy with gemcitabine and cisplatin followed by avelumab for maintenance therapy is recommended
- If patients undergoing systemic chemotherapy are not eligible for cisplatin-containing therapies, gemcitabine and carboplatin are recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies, pembrolizumab is recommended
- If patients undergoing systemic chemotherapy are not eligible for any platinum-containing therapies and their tumors express PD-L1, atezolizumab is recommended
- Palliative care with radiation or surgery may also be recommended1
Recurrent Bladder Cancer
For persistent, recurrent bladder cancers, more aggressive treatment strategies can be employed. Systemic, combinatorial chemotherapies are recommended. MVAC; high-dose MVAC; cisplatin, methotrexate, and vinblastine; and gemcitabine with cisplatin or carboplatin are all combinatorial chemotherapy options for recurrent bladder cancer. Targeted treatments — including enfortumab vedotin, erdafitinib, or ramucirumab — may be appropriate for this situation.3
- If the tumor is Tis, Ta, or T1, intravesical therapy with BCG is recommended
- Cystectomy and TURBT can also be options for recurrent Tis, Ta, and T1 tumors
- If the recurrent tumor has invaded muscle, cystectomy is recommended
- If the muscle-invasive tumor is not operable, radiation and cisplatin alone or low-dose gemcitabine if patient is not eligible for cisplatin-containing therapies is recommended
- Muscle-invasive tumors can also be eligible for systemic chemotherapy (recommendations for advanced systemic chemotherapy have been described above)1
References
1. NCCN Clinical practice guidelines in oncology (NCCN GuidelinesⓇ), bladder cancer. National Comprehensive Cancer Network. Updated February 9, 2023. Accessed April 18, 2023. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
2. Key statistics for bladder cancer. American Cancer Society. Updated January 13, 2023. Accessed May 2, 2023. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html
3. Bladder cancer stages. American Cancer Society. Updated January 30, 2019. Accessed April 19, 2023. https://amp.cancer.org/cancer/bladder-cancer/detection-diagnosis-staging/staging.html
4. Bladder cancer prognosis and survival rates. National Cancer Institute. Updated February 16, 2023. Accessed April 18, 2023. https://www.cancer.gov/types/bladder/survival
5. Bladder cancer treatment. National Cancer Institute. Updated February 16, 2023. Accessed April 18, 2023. https://www.cancer.gov/types/bladder/treatment
6. Cisplatin. Prescribing Information. Fresenius Kabi USA, LLC; 2017. Updated December 31, 2019. Accessed April 18, 2023.
7. Doxorubicin Hydrochloride. Prescribing information. Amneal Pharmaceuticals LLC; 1974. Updated February 25, 2021. Accessed April 18, 2023.
8. Fluorouracil. Prescribing information. Spectrum Pharmaceuticals, Inc.; 1962. Updated July 2016. Accessed April 18, 2023.
9. Gemzar. Prescribing information. Eli Lilly and Company; 1996. Accessed April, 18, 2023.
10. Jelmyto. Prescribing information. UroGen Pharma, Inc; 1974. Updated August 2020. Accessed April 18, 2023.
11. Thiotepa. Prescribing information. MSN Private Laboratories Private Limited; 1959. Updated November 2019. Accessed April 18, 2023.
12. Valstar. Prescribing information. Endo Pharmaceuticals Solutions Inc.; 1981. Updated October 2019. Accessed April 18, 2023.
13. Bavencio. Prescribing information. EMD Serono, Inc.; 2017. Updated July 20, 2022. Accessed April 18, 2023.
14. BCG. Prescribing information. Organon; 1990. Updated 2009. Accessed April 18, 2023.
15. Padcev. Prescribing information. Seagen Inc.; 2019. Updated April 1, 2023. Accessed April 18, 2023.
16. Opdivo. Prescribing information. E.R. Squibb & Sons, LLC.; 2014. Updated February 2023. Accessed April 18, 2023.
17. Keytruda. Prescribing information. Merck Sharp & Dohme LLC.; 2014. Updated April 3, 2023. Accessed April 18, 2023.
18. Trodelvy. Prescribing information. Gilead Science; 2020. Updated February 9, 2023. Accessed April 18, 2023.
19. Balversa. Prescribing information. Janssen Products LP; 2019. Updated February 3, 2023. Accessed April 18, 2023.
20. Adstiladrin. Prescribing information. Ferring Pharmaceuticals; 2022. Updated December 2022. Accessed April 18, 2023.
21. Zhu C, Liu J, Zhang J, et al. Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma. Oncotarget. 2017;8(41):71117-71127.
Author Bio
Hannah Actor-Engel, PhD earned a Bachelor of Science degree in Neural Science at New York University, and she received her PhD in Neuroscience at the University of Colorado. She is a multidisciplinary neuroscientist who is passionate about scientific communication and improving global health through biomedical research.
