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Genitourinary Cancer – 12 – Prostate Cancer – Metastatic

Genitourinary Cancer  – 12

(All the articles published in past are available at www.shyamhemoncclinic.com/blog/)
Question: Thank you Chiragbhai for several interesting points about treatment of Metastatic prostate cancer. 1. Even after hormone resistance, there are several options now. Chemotherapy improves overall survival, is well tolerated in a significant number of elderly, more so with some practical modifications. 2. New options abiraterone and enzalutamide are both well tolerated, convenient as they are given orally, and improve overall survival. 3. Thank you for clarifying role of bicalutide and its duration, as it is widely used in India.
Any other tips about new options that you would like share with our readers?
Answer: Yes, one more option available is Cabazitaxel. This is a chemotherapy agent which works after docetaxel resistance. And improves overall survival even in this very difficult to treat disease. Drug has not been used very widely however, due to myelosuppression and due to availability of other options as we saw earlier.
Que: Based on what we discussed so far, eventually all these patients in stage 4 do progress, in spite of all new options. What do you do at that time?
Ans: Stage 4 patients are not cured. However new options have significantly increased their survival, and reduced the time where they are living with lot of symptoms. Even in HRPC stage, they are now surviving beyond 2-3 years, and with reasonable quality of life. A number of patients die due to their other comorbidities, age and not from prostate cancer. However a substantial number need active palliative care related to prostate cancer, either while on these new options or much more likely when they have also failed.
Main issues in palliative care at this point are around Pain, Urinary issues (retention, bleeding), fatigue, myelosuppression, treatment related side effects, weight loss, loss of appetite, and others.
Several options exist for these issues, apart from standard palliative care principles.
Bone metastases related pain: can be handled by various specific options, apart from analgesics.
1. Zoledronate: a bisphosphonate given once every 3 weeks to 3 months. New studies show 3 months is equivalent to more frequent administration. Cannot be used be with high creatinine.
2. Denosumab: a RANK ligand inhibitor. Similar efficacy and role as zoledronate but can be given with high creatinine. Both agents can cause hypocalcemia, mostly mild, rarely symptomatic.
Above two options reduce osteoclast activity, hence reduce rate of fractures and also provide pain relief. Pain relief however is generally modest and not effective for extensive or late stage disease.
3. Radiotherapy: short course radiotherapy is probably the most effective and long lasting treatment for bone pain. Given as outpatient, over 1 to 10 fractions. For a small area, it is easy to deliver and widely used. Less widely used but good option is for a large area, known as hemibody radiation. Covering bones of half of the body. In general radiotherapy is well tolerated, is outpatient treatment, and is fairly cheap or even free at government cancer centers. Good option for patients coming from distance, even frail patients. Disadvantage is need for radiotherapy equipment, and myelosuppression. Later precludes use of future chemotherapy for example. Hence this is to be used when systemic therapy options are not feasible or completed, especially use of hemibody radiation. We have used hemibody radiation in few of our patients with good results. Focal radiotherapy to few bone sites has been used extensively by us.
4. Radionuclide injection: this is another good option in advance stages, well tolerated, convenient (a single intravenous injection effect lasts for several months, given as outpatient), not very expensive. Disadvantage is limited availability. However large cities in India with nuclear medicine facilities are likely to have this. We have used Sumarium injection in few of our patients with good results. Unlike radiotherapy which works only at directed site, this drug goes to all sites of bone metastases. Can be repeated as well after few months. Myelosuppression is generally mild to none.
Other approaches that work for some disease control, without improvement in overall survival, but may provide symptomatic relief are. Also a palliative care expert should be involved in care where available, or patient referred at least once to an expert center, such as Karunalay.
1.Mitoxantrone: well tolerated chemotherapy agent, cheap, outpatient administration.
2. Steroids: prednisone, dexamethasone. 3. Estrogens, progesterones. 4. Androgen withdrawl – if not tried earlier. Generally used first before other options. 5. Radiotherapy for bleeding in urine.
August 15th 2018.

Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001.                                                                  Diplomate American Board of Oncology and Hematology. Ahmedabad.                                    drchiragashah@gmail.com

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