people atezolizumab (in pd-l1+)gemcitabine + carboplatinpembrolizumab (in pd-l1+) atezolizumab (atezolizumab 1200 mg iv) every 3 weeks gemcitabine (1,000 mg/m2 iv) - day 1,8 carboplatin (4.5 × ) - day 1 and every 3 weeks pembrolizumab 200 mg every 3 weeks second line treatment bladder cancer that is refractory or shows progression after platinum-based chemotherapy can be treated with second-line chemotherapy or immunotherapy. the most commonly used second-line chemotherapy is single-agent regimes of taxanes (paclitaxel, nab-paclitaxel and docetaxel). other single-agent regimes include vinflunine, a third generation vinca alkaloid (approved in europe), gemcitabine, pemetrexed, oxaliplatin, and ifosfamide. side effects of vinflunine include neutropenia, constipation, fatigue and anemia and has limited its use as a second line agent. response to second-line chemotherapy occurs in 5%–20% people. median progression free survival with second-line chemotherapy is 3–4 months. in people with fibroblast growth factor receptors (fgfr) mutations and fail standard platinum based chemotherapy erdafitinib can be used. erdafitinib has shown a response rate of 40% in these patients. five immunotherapy agents has been approved in the us for use in metastatic bladder cancer. they act by inhibiting programmed cell-death protein 1 (pd-1) or programmed cell-death ligand 1 (pd-l1). pembrolizumab and nivolumab, and are inhibitors of programmed cell-death ligand 1 (pd-1). avelumab, atezolizumab and durvalumab are inhibitors of pd-l1. pembrolizumab probably improves overall survival a little and may slightly improve quality of life for people with urothelial cancer that has worsened after initial treatment when compared with continued chemotherapy. however, pembrolizumab may have only minimal effects on the rate of death resulting from treatment or the rate at which the cancer advances. pembrolizumab may cause less serious side effects than chemotherapy. dosage and schedule of second-line immunotherapy regimens for metastatic bladder cancer(in pd-l1+). atezolizumabnivolumabpembrolizumabdurvalumabavelumab atezolizumab 1200 mg iv every 3 weeks nivolumab 3 mg/kg iv every 2 weeks pembrolizumab 200 mg every 3 weeks durvalumab 10 mg/kg every 2 weeks for 12 months avelumab 10 mg/kg iv every 2 weeks surveillance and response contrast enhanced ct is used to monitor lung, liver, and lymph node metastases. a bone scan is used to detect and monitor bone metastasis. treatment response is measured using the response evaluation criteria in solid tumors (recist) into one of the following groups; response (complete or partial), stable disease and progressive disease. prognosis people with non-muscle invasive tumors have a favorable outcome (5-year survival is 95% vs. 69% of muscle invasive bladder cancer). however, 70% of them will have a recurrence after initial treatment with 30% of them presenting with muscle invasive disease. recurrence and progression to a higher disease stage have a less favorable outcome. survival after radical cystectomy and pelvic lymph node dissection is dependent on the pathological stage. if the disease has not spread to the lymph node and is limited to the bladder (t1 or t2, n0) the 5-year survival is 78%. if it has spread locally around the region of the bladder with no lymph node involved (t3, n0) then the 5-year survival drops to 47%. in disease with lymph node spread (n+, irrespective of t stage) the 5-year survival is 31%. locally advanced and metastatic disease drastically decreases survival, with a median survival of 3–6 months without chemotherapy. cisplatin-based chemotherapy has increased the median survival to 15-months. however, the 5-year survival is still 15%. there are several prognostic factors which determine cancer specific survival after radical cystectomy. factor with detrimental effect of cancer specific survival are old age, higher tumor grade and pathological stage, lymph node metastasis, presence of lymphovascular invasion and positive soft tissue margin. lymph node density (positive lymph nodes/total lymph nodes observed in the specimen from surgery) is a predictor of survival in lymph node positive disease. higher the density lower is the survival. quality of life after radical cystectomy, urinary and sexual function remain inferior to the general population. people who have a neobladder have better emotional function and body image compared with ones with cutaneous diversion (who need to wear a bag to collect urine over their abdomen). social factors such as family, relationships, health and finances contribute significantly for determining good quality of life in people who have been diagnosed with bladder cancer. a high percentage of people with bladder cancer have anxiety and depression. people who are young, single and have advanced clinical disease have a high risk for getting diagnosed with a psychiatric illness post-treatment. people with psychiatric illness post treatment seem to have worse cancer specific and overall survival. epidemiology top countries by new cases of bladder cancer per 100,000 (2018) rankcountryoverallmenwomen 1lebanon25409 2greece21404 3denmark18298 4hungary17279 5albania16276 5netherlands16268 7belgium16276 8italy15276 9germany15266 10spain15276 age-standardized death from bladder cancer per 100,000 inhabitants in 2004. no data less than 1.5 1.5–3 3–4.5 4.5–6 6–7.5 7.5–9 9–10.5 10.5–12 12–13.5 13.5–15 15–16.5 more than 16.5 globally, in 2017, bladder cancer resulted in 196,000 deaths, a 5.4% (age adjusted) decrease from 2007. in 2018, the age adjusted rates of new cases of bladder cancer was 6 cases per 100,000 people and age adjusted death rate was 2 deaths per 100,000 people. lebanon and greece have the highest rate of new cases. in lebanon, this high risk is attributed to high number of smokers and petrochemical air pollution. the risk of bladder cancer occurrence is four times higher in men than in women. smoking can only partially explain this higher rates in men in western hemisphere. one other reason is that the androgen receptor, which is much more active in men than in women, may play a part in the development of the cancer. this hypothesis is also supported by the fact that men undergoing androgen suppression therapy for unrelated reason seem to have a lower risk of developing bladder cancer. in africa, men are more prone to do field work and are exposed to infection with schistosoma, this may explain to a certain extent the gap in incidence of squamous cell cancers in areas where bladder cancer is endemic. however, women present with more aggressive disease and have worse outcomes than men. this difference in outcomes is attributed to numerous factors such as, difference in carcinogen exposure, genetics, social and quality of care. one of the common signs of bladder cancer is hematuria and is quite often misdiagnosed as urinary tract infection in women, leading to a delay in diagnosis. moreover, as mentioned earlier psca gene may play a role in aggressive tumors in women. canada bladder cancer is the sixth most common cancer accounting for 3.7% of the new cancer cases. in 2018, 30,700 canadians were living with bladder cancer, 9160 new cases were diagnosed and 2467 died from it. in 2019, it is estimated that 11,800 new cases will be diagnosed and 2500 will die from it. among the 11,800 new cases, 9100 will be in men and 2700 in women. of the 2500 who would die from it, 1800 will be men and 700 will be women. china bladder cancer is the 14th most common cancer and 16th most common cause of cancer death. in, 2018 it accounted for 82,300 new cases and 38,200 deaths. the number of new cases is comparatively lower compared to its western counterparts. majority of the people are diagnosed with non-muscle invasive disease (75%) and the rest have muscle invasive disease (25%). carcinoma in situ was present in only 2.4% of the cases. europe in 2015, 131,000 news cases were diagnosed in the european union with 40,000 deaths. it is the 5th most common cancer and 9th most common cause of cancer deaths.. the 5-year relative survival for bladder cancers diagnosed between 2000 and 2007 is 69%. geographic variation is seen in survival rates with 5-year survival rates of 75% in northern to 65% in eastern europe. united kingdom bladder cancer is the ninth most common cancer in the uk accounting for 2.7% of all the new cancers cases. in 2018, there was 12,200 new cases and 6100 people died from it. united states in the united states in 2019 80,470 cases and 17,670 deaths are expected making it the sixth most common type of cancer in the region. bladder cancer is the fourth most common type of cancer in men and the 12th most common cancer in women. around 62,000 men and 19,000 women are diagnosed with bladder cancer in 2019. between 2012 and 2016 annual rate of new bladder cancer cases decreased by one percent per year.