Genitourinary Cancer – 19 – Bladder

Genitourinary Cancer PART – 19
(All the articles published in past are available at www.shyamhemoncclinic.com/blog/)
Question: Thank you Chiragbhai for explaining important points related to bladder cancer. 1. Superficial cancers have a fairly different prognosis and treatment options. Transurethral resection, intravesical chemotherapy, BCG instillation are most used modalities. 2. A proper deep biopsy is extremely important to ensure diagnosis of invasive stage. CT scan is important for proper staging.
Now can you tell us about treatment of invasive bladder cancer.
Ans: The gold standard has been surgery i.e. radical cystectomy. Same as many other cancer types, removal of complete or partial organ with nearby lymph nodes, and in some cases nearby organs, is the standard practice. For example, radical cystectomy involves removal of prostate and seminal vesicles. In women, it involves removal of uterus, ovaries, cervix, part of vagina. Depending on stage of disease, it can provide high cure rates. However, as you can imagine, bladder function is critical and hence urine diversion procedures have to be done along with bladder removal surgery. There are many techniques. Studies seem to show comparable quality of life for most different techniques.
Que: Organ preservation has been possible in several cancers, using chemoradiation, without surgery. Why not in bladder cancer?
Ans: Very good question. This has come late in bladder cancer compared to many organ types like larynx, lung, esophagus etc. However it is a standard option now, but requires careful patient selection. It also requires very good team work between surgeon and chemoradiation team. This is the same concept as in larynx cancer. After chemoradiation, a critical evaluation time point is 2-3 months. If there is residual disease at this time, salvage with radical cystectomy must be done immediately to prevent risk of metastatic disease. If there is complete remission, close observation is to be done. As some patients do relapse later i.e. after initial remission, and would benefit from salvage cystectomy.
Que: What about role of chemotherapy in bladder cancer?
Ans: For stage 2, 3 patients, perioperative chemotherapy is very important. As per NCCN and other guidelines, preoperative chemotherapy is preferred, showing improvement in overall survival. For those who did not receive preoperative chemotherapy, postoperative can be given. All these regimens are cisplatin based, as other combinations (including even carboplatin) do not show improvement in survival. Most common ones are gemcitabine cisplatin AND ddMVAC (dose dense MVAC).
A small but significant number do present with metastatic disease or develop metastases after initial therapy. These patients benefit from palliative chemotherapy. Carboplatin can be used at this point, for both better tolerance and also because many patients don’t have good kidney function at this stage. Taxane based combinations are also an option.
Most important advance in systemic therapy for metastatic bladder cancer has been immunotherapy with check point inhibitors. They are much easier to tolerate and provide significant clinical advantage including increased overall survival, and hence they are approved for use after failure of cisplatin based chemotherapy. Overall, only about 30% of patients respond to these agents, and only 5-10% of these are complete response. However, some of the responses are very durable, something unique to check point inhibitors. Side effects are much lower compared to chemotherapy. But importantly, they are of very different type. Hence careful monitoring for early diagnosis of these unique side effects is important. Main concern is inflammation of any organ, such as lung, colon, and peculiar is inflammation of endocrine organs (thyroid, pituitary, insulin producing cells…). These are frequently of low grade. But about 5% can be high grade, requiring early recognition and treatment with steroids as well as holding the drug. Hypothyroidism is more common. Occasional patients may even develop type 1 diabetes mellitus. Most important limitation for routine use in India is cost of these drugs, minimum being about Rs 2 lac per month. Drug may take up to 3 months to show response, and has to be continued for two years as per guidelines, provided it continues to control disease. A minimum of one year is recommended in responding patients for meaningful benefit, if patient can afford.
They are also used as first line in patients who are not candidates for chemotherapy due to poor renal function or fitness. Ones available in India are Nivolumab, Pembrolizumab, Atezolizumab. They are however not indicated as first line otherwise, as clinical trials showed poor survival compared to cisplatin containing chemotherapy when used as first line.
April 15th 2019. Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. drchiragashah@gmail.com