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Advanced Cancer

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Targeted therapy and inherited mutations
Has your doctor talked to you about targeted therapy for your prostate cancer? It pays to know the facts so you can understand the situation and decide what’s best for you. Let’s take a closer look together.

Overview

The term “advanced prostate cancer” describes not just one type of condition, but many. This may include one of the following prostate cancer:

Locally advanced cancer – When it begins to spread beyond the prostate without going too far away. It may have barely crossed the capsule boundaries, but it may also have reached neighbouring tissues, such as the bladder, external sphincter and rectum.

Recurrent cancer – When it reappears after initial treatment (surgery, radiotherapy/brachytherapy) with or without metastasis.

Metastatic cancer – When it has spread to other parts of the body away from the prostate. More often, metastases of prostate origin are established in the pelvic lymph nodes and bone.

Castrate-resistant cancer or CRPC – When it continues to progress despite hormone therapy.

Some of these cancers can be cured. Others will be controlled; the various treatments can successfully control the progression of your cancer for several years. In the presence of metastases, they can reduce your symptoms and pain. For cancers that cannot be cured, specialists increasingly agree on the chronic nature of this disease thanks to advances in research and the emergence of new molecules.

Treatment objectives

The treatment chosen will depend on the type of advanced cancer and will aim to either cure it or slow its long-term progression. The choice of treatment will depend on various factors:

  • Age and life expectancy
  • Gleason score, stage, and PSA level
  • Treatments already received
  • Location of your recurrence
  • Existing conditions such as heart disease or diabetes
  • Symptoms
  • Personal preferences

Locally advance cancer

Locally advanced prostate cancer is not synonymous with metastasis. It is defined as a cancer that has begun to spread beyond the prostate without going too far. It may have just passed the boundaries of the prostate (the capsule), but it can also affect neighbouring regions of the prostate (vesicles seminal, bladder, rectum, pelvic wall). The best treatment will depend on the extent of your cancer, its risk of progression, your PSA level, your age and general health. It may include:

Radiation therapy – Radiation therapy is often used to treat locally advanced prostate cancer. It is usually administered in combination with hormone therapy.

Hormone Therapy – It can be offered before, during, or after radiation therapy. It can be used as the sole treatment if you cannot undergo radiation therapy or surgery.

Surgery – Open or robotic surgery will be an option depending on the extent and risk of progression of your cancer, as well as your life expectancy. Radical prostatectomy with extensive lymph node dissection may be considered as an alternative to hormone therapy.

What you need to know

If the doctor is certain that your cancer has spread outside your prostate, a radical prostatectomy or radiotherapy alone will not be enough to treat the locally advanced prostate cancer.

For example, T3+ (the cancer has spread beyond the prostate capsule) and T4 (the tumour has reached neighbouring tissues, such as the bladder, external sphincter and rectum) stage cancers are no longer limited to your prostate, even if no metastases are detected, as confirmed by bone scan and other diagnostic tests.

In such cases, hormone therapy is often used as a complement to radiotherapy. It should be noted that radiotherapy is generally used for the T3+ and T4 stages because these stages are too advanced for surgery.

  • Hormone therapy will be prescribed in combination with radiotherapy for a limited period of time.
  • The medical follow-up and regular dosage of your PSA allow you to judge the stabilization of the cancer. Your PSA level may never move again. If your PSA levels start to rise again, hormone therapy could be prescribed again.

If your cancer is considered to be at high risk of progression, you may consider participating in a research study. Talk to your doctor about it. He or she will advise you if a clinical trial could be beneficial to you.

Recurrent cancer

Cancer that comes back after a radical prostatectomy or radiation therapy—whether or not these treatments were used in conjunction with hormones —is considered to be advanced cancer. Whether or not the recurrence is local or metastatic, it is still considered to be advanced.

Local recurrence: your cancer can reappear in the same place it was before your first treatment. Local recurrence means that some cancerous cells survived treatment and remained in the prostate region

With metastases: your cancer may show up in another part of your body. This is called a metastatic recurrence.

Recurrences can occur at any time. After treatment, the risk of recurrence decreases as the years pass. Although you often hear that the “magic number” of years is five, but there is no absolute guarantee, which is why long-term follow-up is still required. See Dealing with Recurrence.

The doctor usually detects a recurrence when your PSA level begins to climb again. The speed at which your PSA level increases (doubling time) with the grade and stage of your removed tumour will help the doctor determine whether it is a local or metastatic recurrence. The higher these factors, the more likely it will be a metastatic recurrence.

In the event of a recurrence of prostate cancer, various treatment options or combinations can be used: radiation therapy, hormone therapy, surgery, chemotherapy, new generation hormone therapy, research protocols, etc. Your doctor is in the best position to suggest a treatment plan that will work for you.

New in terms of nuclear imaging test

The PSMA PET scan is a new type of nuclear imaging test that uses radiotracers. This method can pinpoint which body parts, other than the prostate, the cancer cells may have spread to. It’s particularly useful in cases where the cancer has come back after surgery or radiation therapy, as indicated by elevated PSA levels.

Currently, PSMA PET scans are limited to specific cases, but they are expected to become more common with time.

Recurrence after radical surgery

In most cases, PSA levels provide an early warning, several months or years before a recurrence is widespread enough to be detected by radiology or during a physical exam

Radiation therapy with or without hormone therapy – In some cases of localized recurrence, it is even possible to completely cure the disease through radiation therapy alone or in combination with hormone therapy.

  • If your recurrence appears to be localized, slow‑growing and not particularly worrisome in any other respect, the doctor may recommend that you forgo treatment altogether. For example, in a case where PSA levels begin to rise five years after an operation, there will likely be no metastasis for another 10 or 15 years.
  • If you are already quite old or you have a short life expectancy, it might be a better idea to avoid or delay treatment instead of introducing hormone therapy that will impair your quality of life.
  • If you are younger and have a longer life expectancy, the doctor will probably take a more aggressive approach and prescribe radiation therapy, either alone or in combination with hormone therapy.

Once the decision has been made to forgo radiation therapy, you can choose to wait for a significant increase in PSA levels before beginning hormone therapy.

If the progression of the disease becomes worrisome at any time, treatment can begin immediately. Every case is unique. You need to weigh the pros and cons of each option carefully in close consultation with your doctor.

Recurrence after radiation therapy

Salvage brachytherapy after initial prostate radiation therapy is an emerging technique that adds to the therapeutic arsenal in cases of localized recurrence. This option should be discussed with your radiation oncologist before making a decision.

Hormone therapy – Hormone therapy is often considered the standard treatment for cancer recurrence after radiation therapy. In the absence of metastasis, intermittent hormone therapy is a valid option. Again, if the recurrence is slow‑growing, the patient can choose to delay treatment.

Surgery – In rare cases, the doctor will recommend a radical prostatectomy to remove your prostate. This only happens if the doctor is convinced that the recurrence is limited to the prostate. This can be known as a catch-up surgery. To make an informed decision, it is important to understand that candidates who undergo this procedure should expect more severe side effects than those experienced with radical prostatectomy as the first treatment.

Focal therapy – Other options are currently being studied: cryotherapy and HIFU. It should be noted that these are not the standard treatments. These approaches are used only when the doctor believes the recurrence is still limited to the prostate. At the moment, neither of these techniques can be considered a viable alternative to standard treatment options for prostate cancer. And since their long-term success is unknown, few health centres in Canada offer them.

Metastatic cancer

Metastatic prostate cancer can be diagnosed in several ways. The patient may present with “systemic” symptoms such as fatigue, weight loss or bone pain.

On the other hand, there may have been a diagnosis of localized intermediate- or high-risk prostate cancer. Following this, additional tests may show that the cancer has already spread to other organs (metastasis).

In all cases, a diagnosis of metastatic prostate cancer is based on the identification of cancer cells in other organs (bones, lymph nodes, liver, etc.). This is generally done using different imaging modalities, including:

  • Bone scan – This is used to detect the presence of cancer cells in your bones, where prostate cancer most commonly spreads.
  • Abdominal-Pelvic CT Scanning – This allows the assessment of intra-abdominal anatomy and the identification of suspicious lesions. Since prostate cancer can spread to your pelvic and abdominal lymph nodes, your urologist will be particularly interested in these small organs of the immune system to see if the cancer has lodged there.

In recent years, several treatments initially used after the failure of hormone injection, such as chemotherapy and/or next-generation hormone therapy in the form of tablets, are now sometimes used when a new diagnosis of metastatic prostate cancer is made (see below). This makes it possible to “hit hard” the cancer at the start and thus keep it in remission for as long as possible.

Nodal metastases

When prostate cancer has reached the lymph nodes, discovered either on imaging when a new diagnosis of prostate cancer is made or after removal of the pelvic lymph nodes which is sometimes done during radical prostatectomy, the standard treatment is usually hormone therapy for life. Major studies published have shown that if hormone therapy is started as soon as lymph node metastases occur, before bone metastases (the most frequent metastases) appear, survival is significantly prolonged.

Your doctor may also suggest a radical prostatectomy with the removal of your pelvic lymph nodes if your lymphatic charge is low, meaning that very few lymph nodes have been diagnosed with cancer.

Sometimes the doctor may prefer to wait and monitor your PSA level. Indeed, in about 10% to 15% of lymph node metastase cases, the PSA rate remains stable for several years.

  • With a medical follow-up every three or six months, the doctor will monitor your situation and intervene as soon as he notices that this rate is starting to rise. He will then have time to react since it will still take several months and even years for the cancer to metastasize elsewhere.
  • In particular, a decision will be made to wait to avoid the side effects of hormone therapy for as long as possible.

Bone metastases

Cancer that has spread to the lymph nodes will eventually attack the bones, particularly the pelvis and spine. If metastases are large enough, the following symptoms can sometimes occur: pain in the lower back or hips, numbness or paralysis of the lower limbs (metastases in the spine can compress the spinal cord), constant fatigue, loss of appetite and paleness (bone metastases can cause anemia). At this point, your bones have become very fragile and susceptible to breakage.

Hormone therapy is prescribed as soon as the doctor observes the presence of bone metastasis, whether or not there is also pain. The treatment is almost always continuous and for life.

Hormone therapy eases the pain and significantly prolongs your life. Additional palliative care can help relieve your symptoms or bone pain.

Ongoing research

It was found that patients lived much longer and that the onset of metastases was delayed if hormone therapy was used in association with chemotherapy, such as docetaxel (Taxotere) or a new generation of hormone therapy, such as abiraterone (Zytiga), enzalutamide (XTANDI), apalutamide (Elreada) – early on rather than waiting for your cancer to stop responding standard hormone therapy.

What 2023 research says – In patients with prostate cancer that has spread significantly throughout the body, treatment options beyond just hormone injections, such as triple therapy (standard hormone therapy, chemotherapy and oral tablets), should be discussed with your doctor. As such, here is a video clip that might interest you with Dr. Aly-Khan Lalani, Medical Oncologist at the Juravinski Cancer Centre and Assistant Professor at McMaster University, in Ontario, Canada, following the ASCO-GU scientific conference in 2023.

As mentioned above, this hits the cancer hard from the start and keeps it in remission for as long as possible.

The combination of new generation chemotherapy or hormone therapy with your standard hormone treatment will depend on whether you have many or few metastases, your risk of cancer progression, your overall health, and the pros and cons. Your doctor would be in the best position to advise you on your treatment plan don’t hesitate to ask questions.

What you need to know

Older forms of hormone therapy are still useful and should continue to be prescribed, but the addition of the new generation of hormonal agents brings important benefits to patients. This class of drugs is also an option that can be used if you have been diagnosed with castration-resistant metastatic cancer (see below).

If your cancer develops resistance to this class of drugs, you may be treated with chemotherapy, radium-223 (Xofigo) (see below), or through a research study if there is one of course.

One thing is certain, your treatment will aim to prolong your life, slow down the evolution of your cancer, relieve your symptoms if you have them, and improve your quality of life.

Castrate‑resistant cancer

Hormone therapy can help keep your cancer under control for a number of years. However, over time, cancer can become hormone‑resistant and begin to grow and spread again, in other words, hormone therapy is no longer effective. Some cells will still respond to hormone therapy which is why it will remain at the center of your treatment.

Treatments for hormone‑resistant cancer do exist but differ depending on whether or not metastases are present or on the speed at which PSA rises.

At every checkup, the doctor will do a blood test to monitor your PSA level while undergoing hormone therapy. If the PSA level starts to rise, the doctor will monitor how long it takes to double. The shorter this period is, the higher the risk of recurrence and the more aggressive the recurrence will be. Your prostate cancer has developed into castration‑resistant prostate cancer.

Castrate‑resistant cancer without metastases

With this type of cancer, metastases are not yet perceptible through diagnostic examinations, although it has already taken place on a microscopic level and will eventually become visible to imaging.

Hormone‑resistant cancer without detectable metastases is currently the most studied area in prostate cancer research.

In patients with a rapid increase in PSA (splitting time <10 months), new generation hormone therapy may be offered. The following treatments may be possible:

1- Apalutamide (Elreada)
2- Enzalutamide (Xtandi)
3- Darolutamide (Nubeqa)

All three agents have reported positive results in delaying metastasis, by approximately 2 years, in patients with rapidly rising PSA levels (a CRPC without metastases at high risk of progression).

In this situation, your doctor will explain the treatment and the side effects that may occur. You may also consider participating in a research study to benefit from new forms of therapy.

Hope and advances in research

Testimonial of Robert and his son, Jean-Marc Evenat (To see our other testimonials, click here.)

Castrate‑resistant cancer with metastases

When prostate cancer is resistant to standard hormone therapy and there is evidence of metastases in examinations, treatment should be initiated. This treatment will depend on several factors including age, comorbidities, the presence of symptoms secondary to cancer, and the rate at which the cancer develops.

For more than 10 years, several studies have approved the use of multiple treatments in patients who have reached this stage. However, these treatments do not cure cancer. Even while undergoing these treatments, one must continue to take standard hormone therapy

1 – Docetaxel/Taxotere (chemotherapy): The first treatment to be approved in this sphere, it provides rapid relief from the side effects of cancer. It is usually administered every 3 weeks by intravenous infusion in the hospital

2 – Abiraterone/Zytiga (hormone therapy): This is a medication taken every day allows for a stronger hormonal castration. Regular blood testing is necessary.

3- Enzalutamide/Xtandi (hormone therapy): This is a medication taken every day that allows for a stronger hormonal castration.

4- Radium-223 Dichloride/Xofigo (radiopharmaceutical): This is a six-week venous infusion radiotherapy that is administered weekly. The drug circulates in the blood, clings to bone metastases, and emits radiation. It is usually reserved for patients with bone metastases only.

5- Cabazitaxel/Jevtana (chemotherapy): This is a chemotherapy usually reserved for after docetaxel fails.

6- Lynparza (PARPi): It is a PARP inhibitor that prevents cancer cells from repairing damage to their DNA, which eventually leads to the death of these cells. See our animated video to understand more about this family of proteins called PARP.

7- Pluvicto (radiopharmaceutical drug): This is a drug that delivers a radioactive treatment directly to the cancer cells to be treated. This type of therapy is sometimes the best option for treating metastatic prostate cancer that no longer responds to other treatments. See our animated video to understand more about this type of treatment.

8- Sipleucel-T/Provenge (vaccine): This is a vaccine developed from the patient’s white blood cells. Sipuleucel-T is a therapeutic vaccine used to treat cancer rather than prevent it. It is extremely expensive and is not currently available in Canada.

Palliative treatment

Additional palliative treatments may be added to reduce your symptoms or bone pain. To relieve pain, bone and other pain, analgesics, treatments to strengthen the bone, and even palliative radiation therapy are prescribed. If you have metastatic cancer, you will also need to take calcium and vitamin supplements D.

Bone Health

Bisphosphonates

Bisphosphonates can be used with prostate cancer that has spread to the bones.

  • Bisphosphonates, such as Zoledronic acid (Zometa), can slow or stop the progression of bone destruction caused by metastases, thus reducing the risk of fractures.
  • Used in patients with CRPC with bone metastases, bisphosphonates reduce the risk of complications due to metastases and limit the use of analgesics and palliative radiotherapy.

Biological agent

A drug called Denosumab (Xgeva) can be used instead of bisphosphonates to slow or stop bone loss caused by bone metastases.

  • Denosumab is a monoclonal antibody that recognizes and attaches to RANKL, a substance located on the surface of bone cells. RANKL contributes to bone degradation. By targeting and blocking RANKL, this degradation is slowed down. Denosumab can help prevent bone complications (fractures, bone irradiation, compression medullary, etc.).
  • It can also help prevent the spread of bone cancer in men with rising PSA levels, but who show no sign of cancer spreading to the bones.

Palliative external radiation therapy

Radiation therapy destroys metastatic cells in the bone that cause pain (in the spine, hips and back, for example). This does not change the course of the disease, but it can provide quick comfort and strengthen the bone, thereby reducing the risk of fractures at the ionized site.

In most cases, palliative radiation therapy is used when pain-relieving drugs are insufficient or the bone has a high risk of breaking. However, because any area of the body can generally be irradiated only once, radiation therapy is usually a last resort.

If the pain returns to the irradiated area, only painkillers and bone-targeted therapy can help. These medications can also be used in combination with radiation therapy.

Palliative surgery

Transurethral resection of the prostate – A transurethral resection of the prostate (TURP) can be an option for hormone‑resistant or androgen‑independent prostate cancer. This type of surgery helps relieve urinary tract obstruction symptoms caused by the prostate tumour.

About palliative care

Symptom control

Pain is not present in all cases of recurrent prostate cancer. However, metastases to bones are common and these are often painful. The palliative care team specializes in pain control in cases where the situation is not straightforward. In this case, the palliative care physician may use a combination of medications (such as opioid analgesics, nonsteroidal anti-inflammatory agents, steroids, bisphosphonates), as well as asking for a radiation therapy assessment. Occasionally the physician will enlist the help of an anesthetist who can perform nerve blocks to reduce pain. Pains due to specific nerve involvement may require the use of medication for so-called “neuropathic” pain, such as gabapentin, tricyclic antidepressants or methadone.

Bladder, stomach and bowel symptoms may arise, requiring specific combinations of medications for their control. Laxatives are almost universally required to combat the side effects of pain killers or the “lazy bowel” that is a frequent complication of prostate cancer. Lymphedema (manifest in prostate cancer as swelling of one or both legs) may also require attention and the prescription of a massage technique known as manual lymph drainage, special bandages or compression stockings. Fatigue is a common symptom. If this is due to anemia, blood transfusions may be recommended. If mobility is reduced, the occupational or physical therapist will prescribe regimes to help maintain functioning and independence.

l’après cancer prostate

If there are psychological or family concerns, the palliative care team is available as much to the family members as to the patient. They can help deal with social and financial worries. This is a time for honesty and openness amongst all concerned, and the palliative care team can help with any communication difficulties. Family meetings are often organized to deal with issues around death and dying. The team is available on a long-term basis to the family members if there are bereavement issues and individuals require grief counselling.

The palliative care team

The palliative care team may be consulted to help control symptoms. The team can help with pain or other symptoms at any stage of the illness. In the later stages, this team may help with advice on how to maximize functioning. Or the team may be called in to help with distressing psychological symptoms.

Read more…

These teams operate in the home setting, in outpatient hospital clinics and on inpatient units. The palliative care network includes hospital services or hospices that can offer institutional inpatient care if there are particularly difficult symptom issues, or if the family cannot manage to give the care required at home. For more information on available services you can consult the Quebec Association of Palliative Care.

The inpatient hospital or hospice teams include:

  • Physicians
  • Nurses
  • Psychologist
  • Physical or occupational therapist
  • Social worker
  • Pastoral worker (spiritual counsellor)
  • Art or music therapist
  • Bereavement counsellor
  • Volunteers

These individuals will work very closely with the patient and family members in an individualized program to help ensure the best quality of life possible. Usually, there are facilities for family members to stay overnight in the patient’s room. Sometimes, after a palliative care admission, the patient and family members feel able to resume home care.

fin de vie et cancer prostate

Maintaining hope

Advanced illness may make people feel hopeless, that all is finished. However, with the re-organization of priorities, there is much to hope for, achieve and even take joy in. One remembers that family, children and friends and whatever legacies one can organize are all important. It is paradoxical that the palliative phase can be a time of hope – not for life prolongation but for high-quality and meaningful interactions. The palliative care team may be called upon to help you achieve this.

Clinical trials

Participating in a clinical trial

One way to access new treatments before they become widely available is to participate in clinical trials.

A clinical trial is a research study that uses volunteers, called participants, to test new ways of preventing, detecting, treating, or managing prostate cancer or other illnesses. Some clinical trials help determine whether or not a new drug or device is effective and safe.

Participating in a clinical trial is a valuable contribution to research as clinical trials answer important questions that can lead to better health outcomes. Participation can be a good way for participants to access free treatments. To learn more about clinical trials speak with your healthcare team.

Finding a clinical trial can be a difficult and tedious process. To address this issue, our partner Q-CROC developed Onco+, a free support service available to anyone looking for an oncology clinical trial in Quebec.

If you would like to learn more about oncology clinical trials in Quebec and consider whether participating in a clinical trial might be an option for you, please visit the website of our partner Q-CROC.

Additional clinical trial sites:

2023 Scientific Expert Opinion

Here are two video clips that might interest you with Dr. Aly-Khan Lalani, Medical Oncologist at the Juravinski Cancer Centre and Assistant Professor at McMaster University, in Ontario, Canada, following the ASCO-GU scientific conference in 2023:

Questions for your healthcare team

To get answers to your questions, you need to be prepared. Before seeing your doctor or nurse, prepare a list of questions about your advanced cancer treatments. Making a list of questions before your doctor’s appointment and putting down on paper what concerns you can help calm you down.

  • Keep a running list of your questions as they come to mind.
  • Take a relative or friend with you.
  • Remember that this is not your only chance to ask questions.
  • Try to accept that uncertainty exists. The doctor does not have a definitive answer to every question.

Making a list of questions before your doctor’s appointment and putting down on paper what concerns you can help keep you calm.

About side effects

  • Will the cancer treatment I receive cause fatigue? If so, how intense will it be?
  • Are there treatments to help control or relieve my fatigue?
  • What options do I have if the treatment is not successful?
  • What are the most likely side effects of the treatments you are recommending?
  • Can other members of the healthcare team help me manage my fatigue?
  • (If you are experiencing fatigue) is my fatigue caused by anemia? If so, how will it be treated?
  • What are the most common side effects? How serious are they
  • How soon will these side effects start and how long will they last?
  • What can I do to manage the side effects?
  • Are there symptoms that I should call you about right away?
  • Who do I call? Who do I call after hours?
  • Under what circumstances would my chemotherapy be delayed or reduced?
  • Why may my chemotherapy be delayed or reduced?
  • What can be done to make sure that my treatment is not delayed or reduced?

Clinical trials

  • Are there any current clinical trials relevant to my condition or treatment?
  • If there are, would I be an eligible candidate for these trials?
  • Is there any particular information I should know about these trials?

Before treatment

  • Is there anything I should do before starting chemotherapy?
  • I take medication regularly for other health reasons. Should I keep taking it?
  • Can I take medicine if I get a cold?
  • Can I take vitamins or herbal supplements?
  • Should I eat before my treatment session? After?
  • Are there special foods I should eat or avoid?
  • Can I drink alcohol (beer, wine, spirits) during my treatment?
  • Can I keep working?
  • Are there activities I should avoid while receiving chemotherapy?
  • Who can I contact if I feel emotionally troubled?
  • Are there symptoms that I should call you about right away?
  • Who should I call? After hours?
  • What support services are available in my area?
  • Are there any ongoing clinical trials that I may want to participate in?

During treatment

  • Should I be having this side effect?
  • How long will side effects last?
  • What can I do about these side effects?
  • Are there symptoms that I should call you about right away?
  • Who can I contact if I feel emotionally troubled?
  • What support services are available in my area?

After treatment

  • Will I need further treatment?
  • Which doctor will be responsible for my follow‑up care?
  • How often do I have to see my doctor once my chemotherapy treatment is finished?
  • Will I need follow‑up tests?
  • What tests will I need and how often?
  • What do I need to watch for?
  • What do I need to report to my doctor?
  • Who do I contact after hours?
  • Will my family doctor be involved in my follow‑up care? How?
  • Can I provide support to patients about to receive chemotherapy?

We are here for you

You have questions or concerns? Don’t hesitate. Contact us at 1-855-899-2873 to discuss with one of our nurses specialized in uro-oncology. They are there to listen, support and answer your questions, and those of your family or your loved ones. It’s simple and free, like all of our other services.

Also take the time to visit each of our pages on this website, as well as our YouTube channel, in order to get familiar with the disease, our expert lectures, our section on available resources, the support that is offered to you, our events and ways to get involved to advance the cause.

 

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Sources and references

Last medical and editorial review: April 2023
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