Overview of the management of bladder cancer in older adults

INTRODUCTION — Bladder cancer is the most common malignancy involving the urinary system. Urothelial carcinoma accounts for 90 percent of bladder cancers in the United States and Europe. In other areas of the world, non-urothelial carcinomas are more frequent. Much less commonly, urothelial carcinomas arise in the renal pelvis, ureter, or urethra.

Bladder cancer occurs primarily in older adults, with over three-fourths or more of new cases detected in patients greater than 65 years old [1]. Older adults appear to have a higher mortality due to urothelial carcinoma than younger individuals [2]. In a study from the United States Surveillance, Epidemiology, and End Results (SEER) database, five-year survival rates declined progressively from 84 percent in those between 65 and 69 years to 60 percent in those 85 and older [3].

Age is a risk factor for the development of bladder cancer. Additionally, older adults with bladder cancer may also have experienced longer periods of exposure to other established risk factors for the development of urothelial carcinoma, such as cigarette smoke and various chemical carcinogens. (See "Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder".)

This topic discusses the evaluation and management of older individuals with urothelial cancer. More general discussions of the clinical presentation, diagnosis, and staging of bladder cancer and an overview of treatment are presented separately.

●(See "Clinical presentation, diagnosis, and staging of bladder cancer".)

●(See "Overview of the initial approach and management of urothelial bladder cancer".)

PATHOPHYSIOLOGY IN OLDER ADULTS — An accurate assessment of an older individual's overall health and physiologic status is critical prior to defining the treatment approach in older adults with bladder cancer.

Older adults have important age-related decreases in physiologic reserves that may alter their tolerance to disease and its treatment [4,5]. Specific physiologic factors need to be considered in planning an optimal therapeutic approach in older adults with bladder cancer including cardiovascular [5,6] and pulmonary function [7], both of which can be impacted by cigarette smoke; renal function [8] and peripheral nerve function, which can affect eligibility for platinum-based chemotherapy, among others; and bone marrow reserve [9], cognitive, and metabolic/nutritional status, which influence treatment candidacy for surgery, radiation, and chemotherapy. (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract", section on 'Defining eligibility for systemic therapy' and "Geriatric nutrition: Nutritional issues in older adults".)

FACTORS INFLUENCING TREATMENT DECISIONS — There are limited randomized data for appropriate age-directed therapies in older adults with bladder cancer. As such, treatment decisions are influenced by multiple clinical factors such as patient comorbidities and functional status and clinical context, among others. Goals of therapy include maintaining efficacy and reducing toxicities. Comprehensive geriatric assessment and multidisciplinary involvement are key to achieving these goals.

Clinical factors — Multiple clinical factors influence the approach to bladder cancer treatment among older adults, including factors that influence surgical candidacy (age or comorbidities), functional status, and whether treatment intent is curative or palliative [10]. Other key items include the physical and mental fitness of the patient, life expectancy, support available from caregivers and friends, and patient preferences and goals of care.

●Age and postoperative mortality – Observational data suggest that postoperative mortality following cystectomy increases with age, which may influence the decision for cystectomy. As an example, one observational analysis found that 90-day mortality rates for patients aged 66 to 69, 70 to 79, and ≥80 years were 6, 10, and 15 percent, respectively [11]. Postoperative mortality rates are generally lower at academic centers of excellence that perform radical cystectomy at high volumes. In another observational study of 804 older adults with bladder cancer treated with radical cystectomy, the 90-day mortality rate at high-volume centers was 3.6 percent [12].

●Comorbidities and surgical candidacy – Data suggest that older adults with more comorbidities are less likely to undergo cystectomy. As an example, in one observational study of more than 2400 patients with muscle-invasive bladder cancer, approximately one-third of patients (38 percent) were 75 years and older, two-thirds (63 percent) of whom had at least one serious comorbid condition [13]. Higher comorbidity was independently associated with a decision not to undergo cystectomy. Patients with one comorbidity were 30 percent less likely to undergo surgery than patients with no comorbidities, and those with two or more comorbidities were 40 percent less likely to have surgery.

●Functional status – Functional status is an important predictor of outcomes in older individuals, including the ability to independently perform the activities of daily living, mobility, and gait speed. (See "Comprehensive geriatric assessment", section on 'Functional status'.)

●Treatment intent – The treatment intent is critical as well; specifically, is the cancer potentially curable, is it symptomatic with symptoms that can be effectively palliated, and what is the likely morbidity of treatment? When considering older adult patients, our approach to treatment planning is to start by considering the clinical context:

•Curable by a combined-modality approach (eg, chemotherapy with surgery and/or radiation therapy [RT])

•Symptomatic but not curable

•Asymptomatic but not curable

•Preterminal or terminal

●Other factors – Other important factors include the patient's physical and mental status, anticipated life expectancy, and socioeconomic issues, such as fiscal and support factors, and patient preferences and goals of care. For example, many older adult patients may have adequate health insurance, but treatment may be limited by ancillary costs or the lack of support or transportation.

Our UpToDate contributors from the Levine Cancer Institute have developed a Senior Oncology Program involving specialist geriatricians, oncologists, and allied health professional support staff who are able to assist in the evaluation of these issues. Based upon these inputs, we formulate a multidisciplinary treatment plan that is tailored to the needs and wishes of the patient and caregivers. This treatment approach is consistent with guidelines from the American Society of Clinical Oncology (ASCO) [14] and the National Comprehensive Cancer Network (NCCN).

Comprehensive geriatric assessment — Older patients should undergo a formal comprehensive geriatric assessment (CGA), particularly if surgery is being considered [15,16]. The key domains included in the CGA include functional status, comorbidity, cognition, nutrition, psychological state, social support, and medication review. Further details on this assessment are discussed separately. (See "Comprehensive geriatric assessment for patients with cancer".)

The CGA includes an evaluation of factors that predispose the patient to increased treatment-related toxicity; it should include functional status, comorbidities, cognitive problems, lack of social support, hearing impairment, history of falls, and diet/nutritional status. The presence of these factors is associated with an increase in six-month mortality and postdischarge institutionalization [17] and a 50 percent increase in postoperative complications [18]. Subsequent interventions based on the CGA can reduce treatment-related toxicity and provide other benefits in older adults with bladder cancer [16,19]. (See "Comprehensive geriatric assessment for patients with cancer", section on 'Potential benefits'.)

Beyond its ability to predict complications related to treatment, a CGA may identify other pragmatic issues that otherwise would not be recognized, such as fatigue, nutrition, or functional impairment [20].

MEDICALLY FIT PATIENTS — For older adult patients who are physiologically fit (ie, maintain a good performance status and have limited or no severe comorbidities), the treatment approach is generally similar to that of younger patients. (See "Frailty".)

However, the context is crucial. For example, the clinician may choose more aggressive therapy if the endpoint of treatment is cure rather than palliation. Although older patients may be at a higher risk for treatment-related complications, survival outcomes for medically fit older patients appear to be similar to results in younger patients [21,22].

Non-muscle invasive bladder cancer — For medically fit older patients with non-muscle invasive bladder cancer, the initial treatment typically consists of a complete transurethral resection of visible bladder tumor (TURBT (algorithm 1)). For those with intermediate- or high-risk non-muscle invasive disease based upon depth of invasion or histopathology, intravesical therapy (such as chemotherapy or Bacillus Calmette-Guerin [BCG]) may be indicated. (See "Overview of the initial approach and management of urothelial bladder cancer", section on 'Non-muscle invasive disease' and "Treatment of primary non-muscle invasive urothelial bladder cancer".)

As a practical consideration, added caution must be applied when repeatedly administering BCG or other intravesical therapies in older adult males because of the risk of coincidental benign prostatic hyperplasia (BPH) and the associated risks of creating false passages during repeated catheterization. In addition, older adult males with BPH may have greater difficulty in maintaining the dwell time of intravesical agents that are irritants, such as BCG, and this should be monitored to ensure efficacy of delivered treatment.

The potential benefit of aggressive treatment of non-muscle invasive bladder cancer in older patients was shown in a Surveillance, Epidemiology, and End Results (SEER) and Medicare study that included almost 24,000 older adult patients (mean age 77 years) [23]. After adjusting for stage, socioeconomic status, and clinical characteristics, BCG therapy was associated with an improvement in overall survival (hazard ratio [HR] 0.87, 95% CI 0.83-0.92), with a trend toward improved bladder cancer-specific survival (odds ratio [OR] 0.90, 95% CI 0.80-1.01). The improvement in survival persisted at 10 years of follow-up. However, only 22 percent of patients were actually treated with BCG within six months of diagnosis, implying a significant negative impact on survival due to ageism.

Muscle-invasive bladder cancer — For medically fit older patients with locally advanced muscle-invasive bladder cancer who are candidates for curative intent therapy, treatment options include neoadjuvant chemotherapy plus cystectomy, cystectomy alone as initial therapy for those not eligible for neoadjuvant chemotherapy, or trimodality therapy (TURBT followed by chemoradiation), using a similar approach for younger patients with muscle-invasive disease, depending upon patient- and tumor-specific factors [2,24] (algorithm 2). Whenever feasible, these patients should be evaluated by a multidisciplinary group that includes surgical, medical, and radiation oncology. (See "Overview of the initial approach and management of urothelial bladder cancer", section on 'Muscle invasive disease'.)

Treatment approach

Surgical candidates — For medically fit older patients who are surgical candidates and eligible for cisplatin-based chemotherapy, we suggest neoadjuvant chemotherapy plus cystectomy rather than cystectomy alone. The addition of neoadjuvant chemotherapy plus cystectomy in older adults is associated with an overall survival benefit in one randomized trial [25]. Initial therapy with cystectomy (without neoadjuvant chemotherapy) may be offered to surgical candidates who are ineligible for cisplatin-based chemotherapy. (See 'Neoadjuvant chemotherapy plus cystectomy' below.)

Bladder-sparing trimodality therapy (maximal TURBT followed by chemoradiation) is a nonsurgical alternative in surgical candidates who prefer bladder-sparing treatment. Although there are no definitive randomized trials comparing neoadjuvant chemotherapy plus cystectomy to chemoradiation, observational data suggest similar disease-specific survival between cystectomy and chemoradiation in appropriately selected patients [26-29]. These data are discussed separately. (See 'Bladder-sparing trimodality therapy' below and "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer".)

Nonsurgical candidates — For medically fit older patients who are ineligible for cystectomy, we offer bladder-sparing trimodality therapy with TURBT followed by concurrent chemoradiation. (See 'Bladder-sparing trimodality therapy' below and "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer".)

Treatment modalities

Neoadjuvant chemotherapy plus cystectomy — The use of neoadjuvant chemotherapy plus cystectomy in medically fit older adult patients is based upon results of the Southwestern Oncology Group (SWOG) 8710 trial, which demonstrated an increase in median survival from 46 to 77 months with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC (table 4B)) [25]. Although the median age of patients in the trial was 63, the survival benefit was also seen in patients over 65 years of age. (See "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer", section on 'Neoadjuvant chemotherapy'.)

●Eligibility for platinum-based chemotherapy – Cisplatin is the backbone of most active chemotherapy combinations used for bladder cancer, both in the neoadjuvant and adjuvant settings. However, platinum agents are associated with significant toxicity, which may increase the complication rate for older adults. (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract" and "Overview of neurologic complications of platinum-based chemotherapy" and "Cisplatin nephrotoxicity".)

Because of the toxicities associated with platinum-based treatment, investigators have sought to define criteria to be used in older patients that would help to define appropriate candidates for treatment [30]. (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract", section on 'Defining eligibility for systemic therapy'.)

The criteria are as follows [30]:

•Creatinine clearance (CrCl) ≥60 mL/minute. However, patients with borderline renal dysfunction (CrCl between 50 and 60 mL/minute) may be offered alternative regimens that utilize a split dose of cisplatin (eg, gemcitabine [1000 mg/m²] and a split dose of cisplatin [35 mg/m²] on days 1 and 8 of a 21-day cycle for four cycles (table 1)).

•Eastern Cooperative Oncology Group (ECOG) performance status <2 (table 2).

•Grade <2 neuropathy.

•No significant hearing loss.

•No clinical evidence of congestive heart failure (New York Heart Association [NYHA] class III or IV (table 3)).

●Choice of neoadjuvant regimen – For fit older adults who are candidates for neoadjuvant chemotherapy, there is no established ideal regimen; options include MVAC (table 4A-B) and gemcitabine plus cisplatin (GC (table 1)). In older patients (age >70 years) and those unable to tolerate MVAC due to medical comorbidities, GC is a reasonable alternative, as the MVAC regimen is more toxic than GC [31].

We do not offer dose-dense MVAC, as there are limited safety data to support its use in older adults. Available data also do not support the use of carboplatin-based regimens in the neoadjuvant setting in older adults or those ineligible for cisplatin-based chemotherapy, and this approach remains experimental. (See "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer", section on 'Neoadjuvant chemotherapy'.)

●Options for urinary diversion – For medically fit older adults who undergo cystectomy after neoadjuvant chemotherapy, options for urinary diversion are similar to those available for younger patients, including both incontinent diversions (eg, ileal conduit (figure 1)) or continent diversions (eg, continent cutaneous diversion (figure 2), orthotopic neobladder (figure 3)). However, observational data suggest that older adults are more likely to undergo incontinent urinary diversion [32,33]. The surgical approach to urinary reconstruction following cystectomy is discussed separately. (See "Urinary diversion and reconstruction following cystectomy".)

Bladder-sparing trimodality therapy — The approach to concurrent chemoradiation in medically fit older adult patients is similar to that of younger patients, as data suggest similar disease-specific survival and complete response rates regardless of age [26,34]. These data are discussed separately. (See "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer", section on 'Patient selection'.)

MEDICALLY FRAIL PATIENTS — For older adults who are medically frail (those with significant comorbidities, cognitive impairment, impaired physical function, etc), the risks of surgery, radiation therapy (RT), and/or chemotherapy must be integrated into an individualized treatment plan. Patients with a limited life expectancy and those who wish to avoid treatment-related toxicity should be offered supportive care and referral for palliative care services. (See "Frailty".)

Non-muscle invasive bladder cancer — For medically frail patients with non-muscle invasive bladder cancer, an individualized approach to treatment is necessary, especially for patients with intermediate- and high-risk disease. (See "Overview of the initial approach and management of urothelial bladder cancer", section on 'Non-muscle invasive disease' and "Treatment of primary non-muscle invasive urothelial bladder cancer".)

●For patients with low-risk disease, complete transurethral resection of visible bladder tumor (TURBT) is generally appropriate. Although typically performed under general anesthesia, this can be performed under regional anesthesia if medical conditions warrant.

●For patients with intermediate- or high-risk disease, our approach is to proceed with intravesical therapy for those at low risk for complications, especially if their life expectancy is measured in years [35], followed by surveillance with cystoscopy, if tolerated.

●For patients with recurrent disease, many are ineligible for or decline radical cystectomy due to frailty. Alternative options include TURBT with perioperative chemotherapy, intravesical therapy, and immunotherapy. The management approach to patients with recurrent or persistent non-muscle invasive bladder cancer is discussed separately. (See "Management of recurrent or persistent non-muscle invasive bladder cancer".)

●For patients with serious comorbidities and/or who are not candidates for treatment for whatever reason, we follow expectantly, if asymptomatic, or refer for palliative and supportive care in the event of symptomatic deterioration. (See "Benefits, services, and models of subspecialty palliative care".)

Muscle-invasive bladder cancer — The therapy of frail older adult patients with muscle-invasive and/or high-grade disease can be complicated, depends on the patient's level of frailty and comorbidities, and requires a multidisciplinary collaboration. In general, initial management includes an assessment of surgical eligibility for cystectomy. Nonsurgical approaches in this population include trimodality therapy, radiation alone, or systemic therapy.

Surgical candidates

Cystectomy — For frail patients who are medically operable and prefer a surgical approach, we suggest primary cystectomy followed by observation rather than other non-curative surgical therapies. (See "Radical cystectomy".)

For such patients, a cystectomy is a treatment approach with curative intent, although the specific surgical approach needs to be carefully evaluated. Less complex procedures require less physiologic reserve, require less operating time, and have a lower risk of blood loss, and thus, may be favored for older or less robust patients. Additionally, we typically offer incontinent urinary diversion with ileal conduit to avoid the need for self-catheterization.

Medically frail patients are at significant risk for postoperative complications and mortality at 90 days following radical cystectomy. Therefore, a careful assessment is critical in order to evaluate whether patients are candidates for surgery. One nomogram that combines age and the Charlson Comorbidity index (table 5) appears to predict 90-day mortality accurately [36] and exceeds the predictive ability of the American Society of Anesthesiology (ASA) score (table 6).

Is there a role for neoadjuvant or adjuvant therapy? — There is a limited role for neoadjuvant chemotherapy or adjuvant therapy in frail patients who undergo cystectomy. Our approach is as follows:

●Neoadjuvant chemotherapy – In rare circumstances, frail patients who are eligible for cisplatin-based chemotherapy may be offered neoadjuvant chemotherapy plus cystectomy. However, this is uncommon due to the associated risks of cisplatin administration. (See 'Neoadjuvant chemotherapy plus cystectomy' above and "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer", section on 'Neoadjuvant chemotherapy'.)

●Adjuvant therapy – We avoid adjuvant therapy for older adult patients who undergo cystectomy since there are limited high-quality evidence to support a survival benefit from this approach after cystectomy for muscle-invasive bladder cancer [37]. Further data on the use of adjuvant therapy for muscle-invasive urothelial carcinoma are discussed separately. (See "Adjuvant therapy for muscle-invasive urothelial carcinoma of the bladder", section on 'Older or frail adults'.)

Nonsurgical candidates

Radiation, with or without concurrent chemotherapy (preferred) — For frail patients who are not surgical candidates or for those who elect a bladder-sparing treatment approach, we suggest radiation with or without concurrent chemotherapy rather than systemic therapy alone. For patients who are ineligible for or decline RT, systemic therapy is a reasonable alternative. (See 'Systemic therapy (alternative)' below.)

For patients who are deemed medically inoperable or for those who elect a bladder-sparing treatment approach, TURBT followed by radiation with or without concurrent chemotherapy is our preferred approach. Several observational studies suggest similar long-term outcomes for concurrent chemoradiation compared with cystectomy-based treatment [26-28]. These data are discussed separately. (See "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer", section on 'Overview of treatment approach'.)

For frail older adult patients with invasive bladder cancer eligible for curative intent therapy, we offer concurrent chemoradiation. Preferred options for chemosensitizing agents include cisplatin [21], fluorouracil (FU) plus mitomycin [38], or gemcitabine [39]. The choice among these treatment options is discussed separately. (See "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer", section on 'Concurrent chemotherapy regimen'.)

Hypofractionated RT, which offers shorter a radiation course than conventional fractionation, may be a particularly attractive option in this patient population. Further details on hypofractionated RT as a method of bladder preservation for muscle-invasive bladder care are discussed separately (see "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer", section on 'Radiation therapy technique'). Frail patients who are ineligible for curative intent chemoradiation due to multiple comorbid states may alternatively be offered abbreviated courses of radiation alone with palliative intent [40,41].

Systemic therapy (alternative) — For frail patients with locally advanced, unresectable muscle-invasive disease who are ineligible for RT, options include palliative systemic therapy using a similar approach to those with metastatic disease (eg, chemotherapy, immunotherapy, or targeted agents). Single-agent palliative RT to the bladder may act as an adjunct to systemic therapies and help ameliorate symptoms and slow tumor growth. All such patients should also receive palliative and/or best supportive care. A multidisciplinary approach involving an experienced urologist, medical oncologist, radiation oncologist, and geriatrician is often the most efficient way of formulating a plan of treatment that maximizes the chance of cure and reduces the risk of toxicity.

RECURRENT OR METASTATIC DISEASE — Although the life expectancy for older adults with locally recurrent or metastatic urothelial cancer is overall limited, the efficacy and tolerability of systemic treatment options continues to evolve. The benefits of treatment must be balanced against the toxicities of any proposed treatment for the individual patient. Given the poor prognosis associated with recurrent or metastatic disease, selection of therapy should account for the goals and preferences of the patient and balance efficacy and toxicity. Further details on the management of metastatic urothelial carcinoma of the bladder are discussed separately (algorithm 3). (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract".)

For frail, older adult patients who are not suitable candidates for systemic therapy or surgery, palliative radiation therapy (RT) to the bladder may be used to reduce the duration of symptoms such as hematuria or dysuria [42]. Although data are limited for this population, palliative RT may also be used to treat limited, symptomatic sites of metastatic disease outside of the bladder, such as bony metastases. (See "Radiation therapy for the management of painful bone metastases".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bladder cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Bladder cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Prognosis for older adult patients with bladder cancer – Bladder cancer is a common disease in older adults, with over three-fourths of new cases occurring in patients older than 65 years. These older patients also appear to have higher mortality after a diagnosis of bladder cancer. (See 'Introduction' above.)

●Factors influencing treatment decisions – Multiple factors impact adherence to treatment guidelines for bladder cancer, including older age, prior treatment for bladder cancer, and the presence of greater comorbidities. In order to provide more appropriate treatment, older patients should undergo a comprehensive geriatric assessment (CGA). (See 'Factors influencing treatment decisions' above and 'Pathophysiology in older adults' above.)

●Medically fit patients – For patients who are medically and physiologically fit (ie, maintain a good performance status and have limited or no severe comorbidities), the approach to treatment is the same as for younger patients (algorithm 2). Although older patients may be at a higher risk for treatment-related complications, survival outcomes for medically fit older patients appear similar to that of younger patients. (See 'Medically fit patients' above.)

•Non-muscle invasive disease – For medically fit patients with non-muscle invasive disease, treatment generally consists of maximal transurethral resection of visible bladder tumor (TURBT). Depending upon risk stratification, this may be followed by intravesical therapy. (See 'Non-muscle invasive bladder cancer' above and "Treatment of primary non-muscle invasive urothelial bladder cancer".)

•Muscle-invasive disease – For medically fit patients with muscle-invasive disease who are surgical candidates and eligible for cisplatin-based chemotherapy, we suggest neoadjuvant chemotherapy plus cystectomy rather than cystectomy alone, as this approach is associated with a survival benefit in randomized trials (Grade 2C). For surgical candidates who are ineligible for cisplatin-based chemotherapy, we offer initial therapy with cystectomy without neoadjuvant chemotherapy. (See 'Muscle-invasive bladder cancer' above and 'Surgical candidates' above and "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer".)

For surgical candidates who prefer bladder-sparing treatment approaches or for nonsurgical candidates, we offer bladder-sparing trimodality therapy (TURBT followed by concurrent chemoradiotherapy). (See 'Surgical candidates' above and 'Nonsurgical candidates' above and "Bladder preservation treatment options for muscle-invasive urothelial bladder cancer".)

●Medically frail patients – For medically frail patients (eg, those with cognitive impairment, comorbidities, or impaired physical function), the risks of surgery, radiation therapy (RT), and/or chemotherapy must be taken into account while developing an individualized treatment plan. We refer such patients to our multidisciplinary Senior Oncology Clinic for geriatric assessment as part of treatment planning. Patients with a limited life expectancy and those who wish to avoid treatment-related toxicity should be offered supportive care and referral for palliative care services. (See 'Medically frail patients' above.)

•Non-muscle invasive disease – For frail patients with non-muscle invasive disease who can tolerate anesthesia, TURBT is generally appropriate. For those with intermediate- or high-risk disease, our approach is to proceed with intravesical therapy for those at low risk for complications, especially if their life expectancy is measured in years. (See 'Non-muscle invasive bladder cancer' above and "Treatment of primary non-muscle invasive urothelial bladder cancer".)

•Muscle-invasive disease – For frail patients with muscle-invasive disease, the approach to treatment depends upon comorbidities, general fitness, and patient desires and preferences. (See 'Muscle-invasive bladder cancer' above.)

-Surgical candidates – For patients who are medically operable and prefer a surgical approach, we suggest primary cystectomy followed by observation rather than other non-curative surgical therapies (Grade 2C). There is a limited role for neoadjuvant or adjuvant chemotherapy in these patients. (See 'Surgical candidates' above and 'Is there a role for neoadjuvant or adjuvant therapy?' above and "Radical cystectomy".)

-Nonsurgical candidates – For patients who are not surgical candidates or for those who elect a bladder-sparing treatment approach, we suggest radiation with or without concurrent chemotherapy rather than systemic therapy alone (Grade 2C). For those who are ineligible for or decline RT, systemic therapy is a reasonable alternative. (See 'Nonsurgical candidates' above.)

●Recurrent or metastatic disease – The life expectancy for patients with metastatic disease is limited, and treatment decisions should take into account the goals and preferences of the patient. (See 'Recurrent or metastatic disease' above and "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract".)

•Medically fit patients – For fit, older adult patients who are eligible for cisplatin-based chemotherapy, initial treatment options include gemcitabine plus cisplatin (GC (table 7)) or, less frequently, methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC (table 4A-B)).

•Frail patients – For frail, older adult patients, including those who are cisplatin-ineligible, initial treatment options include carboplatin-based chemotherapy regimens, immunotherapy, single-agent chemotherapy, and palliative RT.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Derek Raghavan, MD, PhD, FACP, FASCO, who contributed to earlier versions of this topic review.