Prostate Cancer

If there is spread of the cancer into the surrounding tissues and organs, the above treatment options of Radical Prostatectomy and/or External Beam Radiotherapy can be utilized. However, depending on the extent of spread, a combination of surgery followed by radiotherapy may be needed, or other drugs may have to be added.

• Radical Prostatectomy can be done followed by androgen deprivation therapy. Androgen deprivation refers to suppression of testosterone production. It consists of using a tablet called Abiraterone Acetate which is an anti-androgen, which is combined with a steroid tablet, prednisolone. If surrounding organs and/or draining lymph nodes are involved with the cancer, then external beam radiotherapy is also added to the treatment regimen.
• External beam radiotherapy in combination with Brachytherapy can be used as a curative treatment option. This requires addition of androgen deprivation therapy, tablet Abiraterone Acetate, in combination with tablet prednisolone, a low dose steroid.
• Androgen deprivation therapy consists of GnRH agonist injections- Leuprolide, or a GnRH antagonist Relugolix, given orally. It may be combined with anti-androgens like Abiraterone Acetate or Enzalutamide. This therapy suppresses testosterone production in the testis and blocks its stimulatory effect on the prostate cancer cells.
• There are clinical trials ongoing to assess the benefits of adding chemotherapy to surgery and radiation, in patients with extensive spread into the surrounding tissues in prostate cancer. Preliminary results appear to show a benefit in those with high-risk disease.
  
  Read about: Uterine Cancer

All prostate cancer patients must undergo molecular tests in the form of Next Generation Sequencing, to look for underlying high risk, hereditary cancer-causing mutations like BRCA1 & BRCA2. The tests also detect the prostate cancers deficient in homologous recombination repair (HRR). The presence of HRR deficiency or detection of the BRCA mutations allows the use of oral tablets called PARP inhibitors in the treatment regimen, thus improving the treatment response and reducing the risk of a recurrence. Other mutations which are cancer causing and may be detected are ATM, CHEK2, PALB2, FANCA, RAD51B, BRIP1 which can be treated with targeted therapy.

Metastatic Prostate Cancers:

This refers to prostate cancers that have spread into the bones, lymph nodes, lungs, liver, etc. Once metastatic, the cancer cannot be cured, but it can be controlled using a combination of targeted therapy options with or without chemotherapy.

A molecular profiling of the biopsy specimen, using next generation sequencing is essential to detect any underlying targetable mutations like BRCA or HRR deficiencies. Both can be treated using PARP inhibitors.

A PSMA PET-CT Scan is needed to document the extent of spread, along with a baseline PSA level, done pre-treatment, to help monitor the response to treatment.

• The initial treatment involves suppressing the testosterone production by performing a surgical castration ( bilateral orchidectomy-removal of the testis) or a medical castration by giving a GnRH Agonist-injection Leuprolide. Both these therapies work to block the stimulatory effect of testosterone on the prostate cancer cells, thereby suppressing the cancer and its ill effects.
•  Injection Denosumab or Zoledronic Acid must be added to treat bony metastasis if present.
•  Painful, bony lesions which are refractory to pain-killers can receive local radiation for pain control.
•  An anti-androgen, usually tablet Abiraterone Acetate with tablet Prednisolone, or tablet Enzalutamide is added post bilateral orchidectomy or with the injection Leuprolide. The 2 therapies act in conjunction to suppress and then maintain cancer control.
• These therapies will control the prostate cancer for a period of time. Monitoring is essential by performing regular PSMA scans and checking PSA levels.
• When disease progression is detected, the treatment line must be changed. Chemotherapy must be added to the Leuprolide and Abiraterone or Enzalutamide combination. A Taxane- injection Docetaxel, is usually the first option. In case of non-response or progression on therapy, another chemotherapy drug- Cabazitaxel can be used. 
• If a repeat biopsy done at the time of progressive disease, shows a poorly differentiated cancer, then chemotherapy using a Taxane and a Platinum gives a good response.
• If the cancer shows mismatch repair deficiency or a high tumour mutational burden, then an Immunotherapy drug like Pembrolizumab can be utilized in the treatment regimen.
• If HRR deficiency or BRCA mutations are detected, PARP inhibitors can be given for the cancer treatment.