Who should take the lead when managing metastatic prostate cancer?

The treatment landscape for men with metastatic prostate cancer is continuously evolving. Therapeutic options are no longer limited to surgical/medical castration, followed by additional hormone-based therapies with no proven survival benefit. A host of treatments are now available, ranging from cytotoxics, through novel androgen-axis targeted treatments, to radionuclide therapies. All these therapeutic options have benefits relating to overall survival and quality of life. Oncologists have extensive experience delivering these newer treatments, having participated in the initial studies, and having had subsequent access to these agents via the National Cancer Drugs Fund. However, now that these agents are available for their licensed indications with minimal restrictions, should urologists also prescribe them? How should the multidisciplinary team now approach the management of metastatic prostate cancer? Will the recently published results for the abiraterone plus prednisolone arm in STAMPEDE (in the metastatic castration sensitive setting) change our multidisciplinary approach, as patients may soon be receiving upfront abiraterone rather than docetaxel?

Our article in Trends in Urology & Men’s Health contains a survey of UK urologists and oncologists about their current and potential roles in the management of metastatic prostate cancer in the context of the rapid expansion in therapeutic options. Read the article here.

What do you think? Let us know your thoughts below.

Comments (5) Add yours ↓
  1. Sandy Tyndale-Biscoe Hon President, Tackle

    Two uses of the term “castration” (or its derivative), once in a way that we can approve (the implication being that castration is a simplistic approach to PCa treatment and something to be avoided) and the second in a way that insults all men receiving ADT.
    Why cannot those involved in treating men with PCa stop insulting their patients by calling them eunuchs? We persuaded NICE to stop doing it (they now, to their credit, not often given, invariably refer to the desease as “hormone resistant” or “hormone sensitive”, not precise terms, but we all kknow what they mean); cannot TRENDS set also an example?

    July 28, 2017 Reply
    • Simon Hughes Consultant Oncologist

      Dear Sandy

      An interesting view-point. As ever, the devil is in the detail.

      The terms “Castration-resistant” and “Castration-sensitive” in this context are being used to describe the cancer rather than the individual fighting the disease. “Castration-resistant” refers to cancer cells that have developed the ability to grow in an environment where the concentration of the male hormone testosterone is <20-50ng/dl. The term “Castration” is used as this is the level of testosterone found in the blood if the testes stop making testosterone (either due to surgical removal, drug suppression, or other disease processes). The key here is that the testosterone levels are not zero – as testosterone is still made in the adrenal glands and by the cancer itself.

      Up until 2011 the terms Castration-resistant and Hormone-resistant were effectively interchangeable – as the hormonal treatments used to treat prostate cancers were largely those that stopped the testicular production of testosterone. Other agents (e.g. oestrogens) were available, but had no proven survival benefit. Therefore, when cancers developed the ability to grow despite exposure to testosterone levels <20-50ng/dl – they were described as Hormone resistant / refractory.

      However, we now have hormonal drugs (abiraterone / enzalutamide) that can treat prostate cancer cells that have acquired the ability to grow at testosterone levels <20-50ng/dl. These cancer cells are resistant to conventional hormonal therapies that only lower testosterone levels to below 20-50ng/dl, but are still sensitive to the new hormonal therapies. This explains why the term Castration-resistant is being applied to such cancer cells – as they are not Hormone-resistant.

      If the labels currently used to describe the properties of prostate cancer cells aren’t acceptable to patient advocate groups then an alternative, clearly defined terminology could be explored (e.g. Type 1 prostate cancer; Type 2 prostate cancer). However, the terminology in use is continuously changing as new treatments / combinations / sequencing strategies evolve. It is likely that before such terminology could be agreed, the terms they are intended to replace will already have become obsolete. With the latest STAMPEDE Trial results, the combination of abiraterone, prednisolone and an LHRH agonist from diagnosis has been shown to dramatically improve the overall survival of men with metastatic prostate cancer. This may lead to a further redefinition of the terminology – I guess a possibility could be: Total Androgen Suppression Sensitive Metastatic Prostate Cancer (TAS-sensitive) and Total Androgen Suppression Resistant Metastatic Prostate Cancer (TAS-resistant).

      A lot of research is being conducted into discovering predictive markers for response to treatment. In future, we aim to be able to test a biopsy / blood sample etc. to determine which therapy/therapies to use next at each point where the cancer develops resistance to the current treatment strategy. This “Personalised” therapy will change the labelling approach as cancer cells will be grouped according to their biomarker profiles rather than just whether they grow despite low circulating testosterone levels.

      One final point regarding your statement that “castration is a simplistic approach to PCa treatment and something to be avoided”. In the context of metastatic prostate cancer – the subject of this Blog and article – castration refers to the surgical OR chemical suppression of the action of the testes. As described above this reduces the circulating testosterone levels to <20-50ng/dl, and remains the most effective treatment we have for this stage of the disease. All the novel agents in use / under development are used in combination with this therapeutic approach. The median survival for men opting to avoid treatments that prevent testicular production of testosterone is about 2 years (EAU Guidelines), whereas the anticipated survival in the STAMPEDE study arm described above is 6.5-7 years.

      I firmly believe that men should be counselled appropriately about the side effects of all treatments used for metastatic prostate cancer, any alternative options available, and the consequences of not receiving treatment. They should also be supported during their treatment in an environment where they can question and change their management decisions where appropriate. Such therapeutic discussions are complex, often challenging and very personal, and need to be conducted in an unbiased way.

      August 7, 2017 Reply
      • Sandy Tyndale-Biscoe Hon President, Tackle

        Dear Simon

        Thanks for the fulsome reply. I was aware of many of the points you make, and the information engineer in me applauds the precise terminology that underlies the usage to which we, patients, object. Unfortunately a good rationale doesn’t remove the inferred (but not implied, I grant) insult. Surely it is not too late for the profession to do the decent thing, as urged by E. David Crawford and Daniel Petrylak in the Journal of Clinical Oncology back in August 2010, when they wrote:
        “However, there have been some concerns expressed by clinicians, and more importantly by patients themselves, that the term castration implies some sort of testicular removal, which has a negative connotation for many men who have this disease.
        Hormone-refractory prostate cancer and androgen-independent prostate cancer did not have this perceived stigma, but in contrast, they have proven to be considerably inaccurate, as second- generation androgen deprivation therapy clinical trials are begin- ning to demonstrate.3,4
        Therefore, we would like to propose that a term such as endocrine- resistant prostate cancer may be a better description to utilize with our colleagues and patients. It is both accurate and less emotionally charged.”

        August 7, 2017 Reply
  2. Larry Goldenberg Dr

    The area of CRPC therapeutics continues to change, and will do so as more therapeutic approaches to both early and late disease appear on our doorsteps. The responsible or prescribing physician must be comfortable with the potential consequences and complications of any drug or device-based therapy he/she uses for the patient. It matters not if it is a med one, rad one or urologist, as long as the patient receives ‘best in class’ therapy. As we move ahead, we will be seeing interventions which might best be administered by someone with experience in imaging the prostate, or someone with radioisotope knowledge or someone who actually understands the details of immunotherapy 🙂

    July 28, 2017 Reply
  3. Culley Carson Professor of Urology

    I agree with Larry above. I think the best approach is a multidisciplinary approach with clinics/conferences with all stake holders in attendance. I know that the Multidisciplinary Urologic Oncology clinic at UNC is great in getting opinions and input from Med Onc, Rad Onc, Urology, social workers, nurse navigators and when needed palliative care specialists. This combined, team approach works best as it uses the combined experience and brain power of all.

    August 21, 2017 Reply

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