Interview with Professor Kurt Miller
Professor Kurt Miller
Chairman, Charité Berlin & Professor of Urology
Benjamin Franklin Medical Center, Berlin, Germany
Q1: What is castration-resistant prostate cancer?
A1: According to the Annals Academy of Medicine’s Guidelines on Management of Prostate Cancer (2013), castration-resistant prostate cancer is a type of prostate cancer that no longer responds to hormone therapy. The male body naturally produces hormones called androgens, which play a role in fuelling the tumour. A castration-resistant prostate cancer diagnosis means that the cancer is resistant to medical or surgical castration that lower androgen and often has spread to other parts of the body (metastatic castration-resistant prostate cancer - mCRPC).
Q2: Is abiraterone acetate plus prednisone treatment a new treatment for mCRPC? How does it work?
A2: Abiraterone acetate is not a new treatment as it was approved by Singapore’s Health Sciences Authority (HSA) in 2012 to treat mCRPC. However, the post-hoc analysis of the Phase 3 COU-AA-302 trial resulted in new data, which showed that abiraterone acetate plus prednisone provided greater overall survival benefit compared to an active control of placebo plus prednisone.
Abiraterone acetate is a prescription medicine that is used along with prednisone to treat men with mCRPC, which is advanced prostate cancer that is resistant to medical or surgical castration that lowers androgen, and has spread to other parts of the body.
It works by inhibiting the production of androgen, which fuels prostate cancer growth, by interrupting the androgen-making process at three key sources: the testes, the adrenal glands and the tumour itself.
Q3: Please share with us the new data about greater survival benefit with abiraterone acetate plus prednisone treatment in men with prostate cancer.
A3: Data from the post-hoc analysis showed that abiraterone acetate plus prednisone demonstrated 11.8 months median life extension (53.6 months vs 41.8 months) when treated in Group 1 patients with early and less aggressive disease. This is in comparison to 4.4 months shown in the final analysis of the COU-AA-302 trial (34.7 months abiraterone acetate plus prednisone vs 30.3 months placebo plus prednisone).
Q4: Could you elaborate some other positive outcomes from the clinical trials of the abiraterone acetate plus prednisone treatment?
A4: In addition to overall survival benefits, the results of this trial demonstrated improvement in three other patient outcomes.
- There is improvement to disease progression with the median time of treatment almost doubling in both groups
Group 1 (less symptomatic stage of disease) – 20.4 months vs 11.2 months
Group 2 (more advanced stage of disease) – 12.3 months vs 7.2 months
- There is improvement in median time to opiate use for cancer-related pain in both groups
Group 1 – not reached vs 41.0 months
Group 2 – 30.5 months vs 19.3 months
- Longer time is taken to initiate chemotherapy as a treatment
Group 1 – increased by 12.7 months (37.0 months vs 24.3 months)
Group 2 – increased by 8.8 months (23.3 months vs 14.5 months)
Q5: Are there any challenges on performing this treatment over other existing treatments (surgery, radiotherapy, chemotherapy)?
A5: Surgery or radiotherapy are not typically used at this stage of the disease. Abiraterone acetate is preferred over chemotherapy in the early stages of mCRPC as it has a lower side-effect profile, and although no head-to-head comparison exists, there is no evidence that shows it being a less effective option than chemotherapy.
Interview with A/Prof. Edmund Chiong
Associate Professor Edmund Chiong
MBBS (Singapore), PhD, FRCSEd, FRCSI, FAMS (Urology)
President of the Singapore Urological Association (SUA)
Senior Consultant, Department of Urology
National University Hospital
Q1: There is a new data demonstrating greater survival benefit with abiraterone acetate plus prednisone treatment in men with metastatic castration-resistant prostate cancer. What do you think is the importance of having the data?
A1: The post-hoc analysis data demonstrates that first and early use of abiraterone acetate plus prednisone can improve a patient’s quality of life and delay the need for additional, more invasive treatment.
Post-hoc analyses such as this may help to identify the patients who would benefit most from therapies and at what disease stage these therapies are most effective.
As men with prostate cancer are living longer, quality of life is an increasingly important factor. This additional analysis may help healthcare professional define the most effective treatment pathway for individual patients.
Q2: From the data of Singapore Cancer Registry, prostate cancer ranked the 3rd most common in Singapore males. Please tell us more about the prevalence and the incidence of prostate cancer cases in this region.
A2: Prostate cancer is the third most common cancer amongst men worldwide, and incidence rates are highest in western countries and lowest in Asian countries. Recent data from Asia have shown steady increase in prostate cancer incidence in the past few decades, with some countries such as Korea, experiencing a rapid rise . According to the Singapore Cancer Registry (2010 – 2014), prostate cancer is currently the third most common cancer in Singaporean males, with an age-standardised rate (ASR) per 100,000 per year of 28.6.
Q3: What are the diagnostic tools for detecting prostate cancer in Singapore?
A3: The prostate is located in front of the rectum and can therefore be examined with a gloved finger in the rectum by a doctor. Apart from digital rectal examination (DRE), blood tests (serum prostate specific antigen or PSA) can help to detect prostate cancer.
To confirm prostate cancer, small pieces of tissue from the prostate gland are removed in the form of a biopsy, and examined under the microscope. In order to determine the extent of prostate cancer, imaging such as CT or multi-parametric MRI scans are performed. A bone scan is also commonly done to see if the bones are affected as this is a common site of distant spread (metastases). There have also been advances in recent years in the use of imaging (mainly MRI and PET scans) to better detect prostate cancer.
Q4: In Singapore, what are the imaging options to monitor prostate cancer? What are the common treatment(s) used for prostate cancer?
A4: Most prostate cancers are first found during testing with a serum prostate-specific antigen (PSA) blood test or a digital rectal exam (DRE). Early prostate cancers usually do not cause symptoms, but more advanced cancers are sometimes first found because of symptoms they cause. If cancer is suspected based on results of screening tests or symptoms, tests will be needed to confirm the diagnosis. The actual diagnosis of prostate cancer can only be made with a prostate biopsy.
Current options available for treating early stage clinically localised prostate cancer include expectant management (such as active surveillance and watchful waiting), radical prostatectomy, radiation therapy and energy ablative therapy. The long term efficacy of surgery as a therapeutic modality is well established.
Radiation therapy is also another commonly used modality. Each modality has its own benefits and risks of side effects, and there is no high level evidence showing superiority of one modality over the other. Active surveillance is now becoming more accepted as an option to manage low risk early disease. Energy ablative therapies (such as cryotherapy and high intensity focused ultrasound) are relatively newer and yet to be fully established as standard treatment. The latter 2 modalities may offer better quality of life and possibly fewer side effects.
However, as there is no single ‘best’ option for all men with localised prostate cancer, management should be individualised. Some considerations before treatment recommendations can be made include patient’s life expectancy, overall health, risk-benefit ratio of treatment, disease risks, quality of life issues and patients’ expectations.
For advanced metastatic disease, Androgen Deprivation Therapy (ADT) or hormonal therapy to reduce blood levels of testosterone to castrate level, is the mainstay of treatment. Newer reports suggest that the addition of chemotherapy to ADT early in the diagnosis of metastatic disease, may improve survival in select men with high volume cancers. There has also been an increase in the number of treatment options for men with advanced prostate cancer who progress while on treatment with ADT (mCRPC), in recent years.
The options include chemotherapy, immunotherapy, abiraterone acetate, enzalutamide and radium-223, all of which have been shown to improve survival in phase 3 studies. The selection of these agents for treatment should also be individualised between the treating physician and the patient.
Q5: How can people prevent themselves from getting prostate cancer?
A5: There are currently no proven prevention strategies. In general, living a healthy lifestyle, eating a well-balanced diet with less animal fat consumption, maintaining a healthy body weight and regular exercise, might help mitigate the risk, but again, there are no conclusive studies to prove that prostate cancer can be prevented. Some studies have also suggested that diet rich in lycopenes (eg. tomatoes) and isoflavonoids (e.g. soy products) may reduce the risk of prostate cancer, but researchers are yet to be certain that these compounds can really affect prostate cancer development. If you notice symptoms, consult a doctor at the earliest opportunity.
Symptoms may include frequent urination, painful urination, increased urination at night, blood in the urine, and difficulty starting and maintaining a steady flow of urine, but these symptoms are not specific to prostate cancer.
Q6: What is the awareness level of prostate cancer among people in Asia Pacific region?
A6: Despite the fact that we have seen a steep increase in prostate cancer being diagnosed at earlier stages, especially in the last 2 decades, nearly 30 per cent of all the prostate cancer cases among Singapore males were found to be in Stage IV or advanced prostate cancer (Singapore Cancer Registry, 2010-2014). Hence, having proper understanding of the disease will benefit men who are at risk.
Awareness of prostate cancer in certain regions in Asia, especially in developing areas, appears to be still lacking, as suggested by the high proportion of advanced disease at initial presentation in these regions.
- Chiong E. Epidemiology of prostate cancer in Asia. Prostate Int 2015: 3: S9