Prostate Cancer Treatment Options by Risk Group

Prostate cancer treatment options range from active surveillance and watchful waiting, through radiotherapy, cryotherapy and radical prostatectomy, to hormone therapy, chemotherapy and lutetium-177 PSMA therapy. The choice follows the risk group: for intermediate-risk and high-risk localised disease, Dr. Amit Goel's first choice is surgery, while metastatic disease is treated according to the site of spread.

Prostate cancer treatment is not a protocol that starts automatically once a biopsy is positive. Dr. Amit Goel, Senior Director & Unit Head - Urology, Kidney Transplant, Uro-oncology, Robotic Surgery, Max Hospital, Gurugram, India, describes it as a field of permutations and combinations. The same diagnosis can lead one man to active surveillance, another to radical surgery followed by radiotherapy, and a third to hormone therapy. The skill lies in matching the treatment to the disease and to the man who has it.

This article follows that decision from the localised cancer through to metastatic and castration-resistant disease. Who is at risk and how the disease presents are set out in the complete guide to prostate cancer symptoms and risk factors, and how the stage and Gleason score are established in the guide to prostate cancer staging and the Gleason score.

What decides the choice of prostate cancer treatment?

Five inputs decide the choice: the stage, the patient's age, his life expectancy, the biopsy findings with the Gleason score, and his other risk factors. Dr. Goel weighs each before choosing a treatment:

• Stage of the disease, from the TNM classification.
• Age of the patient.
• Life expectancy.
• The biopsy findings and Gleason score, which describe how aggressive the tumour is.
• The patient's other risk factors.

No single input settles the question. It is the interplay among them, rather than any one variable, that leads Dr. Goel to call prostate cancer one of the most difficult cancers to treat.

Prostate cancer treatment options at a glance

The treatment spectrum runs from monitoring, through local treatment of the gland, to systemic therapy. Dr. Goel laid it out to show its breadth:

• [Radiation therapy](/treatment-cost/radiation-therapy-radiotherapy), either brachytherapy (radioactive sources placed inside the prostate) or external beam radiotherapy.
• Cryotherapy, which destroys tissue by freezing.
• Androgen deprivation therapy, which suppresses the action of testosterone.
• [Chemotherapy](/treatment-cost/chemotherapy), with docetaxel and cabazitaxel.
• Radical prostatectomy, by open, laparoscopic or robotic technique.
• Watchful waiting and active surveillance, in which the cancer is monitored rather than treated immediately.

Some of these are used for localised disease and others for metastatic disease, and many are combined. Faced with that range, the treating urology team needs a structured way to decide.

How prostate cancer risk groups are assigned: D'Amico and CAPRA

Prostate cancer is placed in a low-risk, intermediate-risk or high-risk group using established tools such as the D'Amico risk assessment scheme and the CAPRA score.

For localised prostate cancer, the two principal options with curative intent are radical prostatectomy and radiotherapy. Choosing between them, or choosing neither, starts with categorising the patient's risk.

Dr. Goel uses established risk tools for this, including the D'Amico risk assessment scheme, which sorts patients into risk categories. The CAPRA (Cancer of the Prostate Risk Assessment) score builds a numerical score from five inputs:

• Age, under or over 50
• PSA at diagnosis
• Gleason score
• Clinical stage
• The percentage of biopsy cores that were positive

The output places the patient in low-risk, intermediate-risk or high-risk disease, and that category, in Dr. Goel's practice, is what determines the treatment that is best for that particular patient. Low-risk disease opens one set of options. Intermediate-risk and high-risk disease call for different modalities.

Surgery versus radiotherapy for prostate cancer

In low-risk disease, randomised trials show equal survival with surgery and radiotherapy; in intermediate-risk and high-risk disease, Dr. Goel reads the evidence as favouring surgery. He summarised the comparative trial evidence by risk category.

Low-risk disease

Randomised controlled trials comparing radiotherapy and surgery for localised prostate cancer show that, in low-risk disease, the two give equal disease-free survival and equal overall survival.

Intermediate-risk and high-risk disease

For intermediate-risk and high-risk disease, Dr. Goel reads the same body of evidence as favouring surgery: in his reading, radical prostatectomy gives the best disease-free survival and overall survival when compared with radiotherapy.

Dr. Goel cited a more recent meta-analysis that addressed high-risk disease specifically. As he summarised it, it found little difference in cancer-specific survival between radical prostatectomy and radiotherapy. On overall survival, however, the patients who had radical prostatectomy did distinctly better. In terms of longevity, Dr. Goel's conclusion is that surgery offers these men the advantage.

This remains an area of active debate. Much of the comparative evidence in higher-risk disease is observational, and international guidelines continue to list both radical prostatectomy and radiotherapy combined with hormone therapy as standard curative options.

Surgery as the first step of a multimodal plan

Dr. Goel's summary position is that surgery is the first-choice treatment for intermediate-risk disease and the first choice for high-risk disease, in the latter case as part of multimodal treatment. Surgery may be followed by hormonal treatment, by radiotherapy, or by both, to give the patient the full benefit of treatment. The prostatectomy is the foundation of the plan, not necessarily the whole of it.

How the operation itself is done, and why the platform and technique affect continence, potency and cancer control, is covered in the comparison of robotic, laparoscopic and open prostatectomy.

Androgen deprivation therapy when surgery and radiotherapy are not possible

In patients whose disease cannot be treated with surgery or radiotherapy, Dr. Goel starts androgen deprivation therapy. This is castration therapy: the patient is given injections that stop the effect of testosterone on his body.

Bilateral orchidectomy remains a valid choice

Hormonal suppression does not have to come from injections. Dr. Goel noted that bilateral orchidectomy, surgical removal of both testes, is still indicated for patients who do not want to spend money on hormone injections, and many patients choose it. In his assessment it works as well as any hormone therapy injection. Where the recurring cost of injections is a burden, the operation delivers the same hormonal effect, and Dr. Goel treats it as a fully legitimate choice rather than an outdated one.

What is castration-resistant prostate cancer?

Castration-resistant, or hormone-resistant, prostate cancer is disease that progresses even though testosterone is suppressed, with a rising PSA as its marker. Hormone therapy works, but often not indefinitely: after a period on androgen deprivation, the PSA starts rising again.

Dr. Goel outlined the treatments available at this stage:

• Newer hormonal agents. Abiraterone is one option; enzalutamide is another.
• Chemotherapy, for patients who need it.

Treating metastatic prostate cancer by site of spread

Metastatic prostate cancer is treated according to where it has spread. That was Dr. Goel's first point when the question was put to him in the masterclass Live Discussion. Prostate cancer can spread to bone or to any visceral organ, and each site calls for a different approach.

Bone metastasis

Bone is the most common site of spread. Dr. Goel's toolkit for it includes:

• Painkillers and steroids for symptom control.
• Bone-strengthening injections where there is pain or a risk of fracture.
• Radiotherapy to the bone where the affected bone is weight-bearing.

Lutetium-177 PSMA therapy for widespread bone metastasis

Among the newer therapies, Dr. Goel singled out lutetium-177 PSMA therapy for patients with widespread bony metastasis. In his experience it works very well, including in patients who have a lot of pain from widespread bone metastases and in patients carrying many comorbidities. That second point matters: the patients most in need of relief from widespread bone disease are often the ones with the most coexisting illness, and Dr. Goel's experience is that this therapy remains effective in them. The therapy is licensed for PSMA-positive metastatic castration-resistant prostate cancer that has progressed after newer hormonal agents and, in most jurisdictions, after taxane chemotherapy.

Visceral metastasis

When the cancer has spread to visceral organs, Dr. Goel sometimes uses chemotherapy. He noted that visceral spread is typically seen later in the disease course, after hormone therapy has been given.

Immunotherapy

Dr. Goel added that immunotherapy has entered the discussion in metastatic prostate cancer. Its established role remains narrow: checkpoint inhibitors have not improved survival in unselected castration-resistant disease, and pembrolizumab is reserved for the small minority of tumours with mismatch repair deficiency or high microsatellite instability.

Prostate cancer treatment by risk group: the pathway at a glance

Taken together, Dr. Goel's approach can be read as a sequence of gates, each opened by a specific finding:

1. Low-risk localised disease. Radiotherapy and surgery give equivalent disease-free and overall survival in randomised trials, and active surveillance and watchful waiting sit on the same menu.
2. Intermediate-risk localised disease. Radical prostatectomy is the first choice, on the strength of what he reads as better disease-free and overall survival than radiotherapy.
3. High-risk disease. Radical prostatectomy remains the first choice, now as the opening step of multimodal treatment that may add hormonal therapy and radiotherapy.
4. Disease unsuitable for surgery or radiotherapy. Androgen deprivation, by injection or by bilateral orchidectomy.
5. PSA rising again on hormone therapy. Castration-resistant disease, treated with abiraterone or enzalutamide, or with chemotherapy.
6. Metastatic disease. Treatment directed by site: bone-strengthening injections, radiotherapy to weight-bearing bone, analgesia and steroids, and lutetium-177 PSMA therapy for widespread bone disease; chemotherapy for visceral spread; and immunotherapy for the small subset of tumours with mismatch repair deficiency.

Why no single regimen fits prostate cancer

Dr. Goel observed that the disease spectrum is so broad that it cannot be captured in a single line. That is the right lesson to draw from the whole treatment pathway. The man with low-risk localised disease, the man with high-risk disease who needs surgery followed by radiotherapy, the man on hormone therapy whose PSA has begun to climb, and the frail man with painful bone metastases are all being treated for prostate cancer. What they need from their clinicians is a sequence of correctly timed decisions, informed by staging, risk scores and the evidence for each option, rather than a single standard regimen.