Advanced Prostate Cancer Treatment: Surgery, ADT and Beyond

Advanced prostate cancer treatment depends on how far the cancer has spread. In the practice of Dr. Yajvender Pratap Singh Rana, oligometastatic disease, limited stage 4 cancer consolidated in the prostate and pelvis, is still treated with surgery followed by androgen deprivation therapy (ADT). Widespread metastatic disease is not operated on: it is controlled with continuous ADT combined with newer drugs, chosen in sequence and increasingly guided by genetic testing.

Dr. Yajvender Pratap Singh Rana is Senior Director - Urology, Uro-Oncology, Andrology and Kidney Transplant at BLK-Max Super Speciality Hospital, New Delhi, India. Doctors in his masterclass asked directly about this end of the disease spectrum: which anti-cancer therapies are best for advanced prostate cancer, where surgery fits, and what role immunotherapy and gene therapy play. This article sets out his answers, along with his guidance for doctors who must manage prostate cancer without access to robotic surgery, PET scanning or a bone scan. For localised and locally advanced disease, start with the complete guide to robotic radical prostatectomy.

Advanced prostate cancer treatment by stage

Treatment differs for each stage of the disease, and Dr. Rana's framework divides it into four groups:

For localised, locally advanced and early metastatic disease, he described surgery combined with androgen deprivation, by injection or by other molecules, as the standard of care. International guidelines, including those of the European Association of Urology, do not recommend routine hormone therapy alongside surgery for localised disease, and still regard surgery for metastatic prostate cancer as investigational outside clinical trials, which is why the choice depends on careful staging and an experienced team. Once the cancer is significantly spread throughout the body, there is no indication for surgery at all. His principle throughout is to individualise treatment to the stage.

Androgen deprivation therapy options: degarelix, leuprolide, relugolix

Continuous ADT is the foundation of treatment for advanced disease. It lowers or blocks testosterone, the hormone that drives prostate cancer growth. Dr. Rana named the main options:

• Degarelix, an injectable gonadotropin-releasing hormone (GnRH) antagonist.
• Leuprolide, an injectable GnRH agonist.
• Relugolix, an oral GnRH antagonist, which he used before surgery in the locally advanced case he presented and which patients tolerate well because it is a daily tablet rather than an injection. The technique article describes a patient treated this way.

He cautioned that ADT alone is not good treatment for disease that could be cured by surgery, because hormone therapy given for a long time carries long-term side effects.

Beyond ADT: doublet, triplet and quadruplet therapy

Dr. Rana stressed that advanced prostate cancer treatment is no longer just ADT. Doctors now combine drugs in doublet, triplet and even quadruplet regimens.

Alongside continuous ADT, patients receive an androgen receptor pathway inhibitor (ARPI), one of the newer anti-androgens, which block the hormone signal more completely. He named abiraterone and enzalutamide, and noted that further molecules in this class are emerging.

Genetic testing, BRCA mutations and PARP inhibitors

Genetic testing now shapes drug choice. When a tumour carries a BRCA mutation, such as a BRCA2 mutation, Dr. Rana's team gives a PARP inhibitor such as olaparib. These drugs exploit the cell's damaged DNA repair machinery to control and kill the cancer cells that carry the mutation.

This, he explained, is how genetics is used in prostate cancer today. Targeted gene therapy, in which the genetic material of cells is altered as treatment, is not in commercial use, and his team does not use it. What they use is genetic testing to select the drugs that work best for a particular subset of patients.

Treatment when advanced prostate cancer progresses

When the cancer progresses despite these lines of treatment, Dr. Rana's next steps are docetaxel chemotherapy, then lutetium-177 PSMA therapy, then immunotherapy.

Chemotherapy

Chemotherapy is effective in prostate cancer. Taxane chemotherapy, led by docetaxel, is the established option, and Dr. Rana's team uses docetaxel-based regimens.

Lutetium-177 PSMA therapy

If the disease still progresses, lutetium therapy comes in. Dr. Rana described it as a newer modality, and said many of his patients are doing reasonably well on it. The principle mirrors the PSMA PET CT scan. Prostate-specific membrane antigen (PSMA) is a protein expressed in large amounts on the surface of rapidly growing prostate cancer cells. In lutetium-177 PSMA therapy, a radioactive lutetium atom is attached to a molecule that binds PSMA, so the radiation is carried into the cancer cells and kills them. He called it internal radiotherapy at the cellular level.

Immunotherapy

Immunotherapy comes after the other lines have failed. Dr. Rana named pembrolizumab as an example and noted that other immunotherapies are also used. Pembrolizumab is approved in prostate cancer only for the small group of tumours with mismatch repair deficiency or high microsatellite instability, which is another reason genetic and molecular testing matters.

Counselling patients with advanced prostate cancer

Counselling, in Dr. Rana's view, must fit the stage of the tumour and give the patient realistic hope. He said so when the moderator pressed the point that counselling is not a neat template. His example: a man whose prostate-specific antigen (PSA) level is above 1,000 has metastatic disease, and the aim becomes keeping the prostate cancer under control with ADT and other molecules. Realistic hope, in that case, means control rather than cure.

Orchidectomy or prostatectomy without robotic surgery

In Dr. Rana's view, orchidectomy is justified for metastatic prostate cancer but not for localised disease, which should be treated by removing the prostate. Several doctors at the session work where robotic surgery, PET scanning and even bone scans are not available. A surgeon from Ethiopia described a setting in which prostate cancer is diagnosed on PSA alone, without biopsy or metastatic work-up, and treated at every stage with bilateral orchidectomy, surgical removal of the testes. Robotic surgery is not available there, he explained, and pelvic surgery is difficult because exposure is hard to obtain. Cancer is also sometimes discovered only on the pathology report after an operation performed for presumed benign enlargement.

Dr. Rana acknowledged the difficulty but was clear on the principle: for localised disease, orchidectomy is not the solution. It gives more harm than benefit. The patient loses his erections, and the organ that holds the cancer stays in place. His practical advice:

1. Stage with what is available. Where bone scans and PET are not available but MRI is, an MRI of the lumbar spine and pelvis can show bony metastases.
2. If there are metastases, orchidectomy is justified. Surgical castration is a legitimate way of delivering ADT in metastatic disease.
3. If there are none, say so plainly. Tell the patient that this is early disease, and that the right treatment is removal of the prostate, not the testes.
4. Point the patient towards proper treatment. Where good treatment for early disease is not yet available locally, the patient should look for treatment overseas. If the family can arrange it, Dr. Rana said, they will be thankful in the long run.

In the end, as Dr. Rana put it, it is the patient who should get the correct treatment. Every exchange from this part of the session is on the Live Discussion page.

Where surgery and systemic therapy meet

The conclusion of the session is that the boundary between surgical and medical treatment of prostate cancer has moved. Surgery now reaches locally advanced and selected oligometastatic disease, and drug treatment for metastatic disease has grown from a single hormone injection into layered regimens increasingly guided by genetic testing. For the referring doctor the decisive variable is the same at both ends: accurate staging, followed by a treatment matched to it.

Approximate costs of surgery for international patients are on the robotic radical prostatectomy cost page. For a second view across the oncology spectrum, Dr. Amit Goel's article on prostate cancer treatment by risk group sets out options for each risk category.