EXPERT INSIGHT

Optimizing the diagnosis and management of prostate cancer in Hong Kong

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Dr. Poon, Ming-Chun Darren

Honorary Consultant in Clinical Oncology,
Hong Kong Sanatorium & Hospital

Honorary Clinical Associate Professor,
The Chinese Univsersity of Hong Kong

Prostate cancer (PCa) has the highest reported incidence rate among common male cancers in Hong Kong during the past two decades.1 It is the fourth leading cause of cancer-related deaths among males in Hong Kong. In 2017, a total of 443 men died from PCa, accounting for 5.2% of male cancer-related deaths.1 Currently, there is an ongoing discussion on enhancing the overall survival of patients with PCa and a number of consensus statements have been published for the effective management of PCa in Hong Kong.2,3 In order to improve the management of PCa further, Dr. Poon, Ming Chun Darren, Consultant in Clinical Oncology at the Department of Clinical Oncology, The Chinese University of Hong Kong, shared his insights on optimizing the diagnosis and management of PCa.

Prostate biopsy: The mainstay of PCa diagnosis

PCa is generally considered as an indolent slow growing disease. Initial work-up consists of serum prostate-specific antigen (PSA) testing and a digital rectal examination (DRE). According to consensus statements published on the management of PCa in Hong Kong, a biopsy is suggested for men with PSA levels between 4 and 10ng/mL, an abnormal DRE test or relevant family history.3 In order to facilitate diagnosis, the free/total PSA ratio or prostate health index can be considered before the biopsy is performed.3

Prostate biopsy remains the gold standard of PCa diagnosis and is considered as the final confirmatory step in the diagnosis pathway, which reveals the PCa type, grading, laterality and focality. Prostate biopsies are traditionally performed using transrectal ultrasound (TRUS) which are associated with considerable rates of infection.4 Furthermore, TRUS-guided prostate biopsies are less sensitive in detecting the anterior prostatic lesions.4 Transperineal prostate biopsies (TPUS) address both shortcomings with TRUS biopsies, but required general anesthesia to carry out the procedures previously.4 Recent techniques offer possibilities to conduct transperineal biopsies under local anesthesia.4

Imaging in the diagnosis and management of prostate cancer

The main aim of using TRUS/TPUS is to guide biopsies rather than to identify the location and extent of PCa.5 Therefore, magnetic resonance imaging (MRI) has been increasingly used to localize PCa more accurately.5 The use of multi-parametric (mp) MRI as a triage test before first prostate biopsy was shown to reduce the unnecessary primary biopsies.6

In patients with localized PCa, who are at a risk of metastasis, the use of computed tomography (CT), MRI or bone scan is recommended to detect distant metastases. Additionally, the use of positron-emission tomography (PET) using prostate-specific membrane antigen (PSMA) ligands was recently introduced.7 PSMA-PET in combination with CT has demonstrated higher sensitivity and specificity in detecting bone and nodal involvements compared with bone scan, MRI, CT or PET-CT using other tracers.7 Therefore, whole-body PSMA-PET-CT is considered as the preferred imaging method for the detection of metastasis in patients with PCa.2

Multimodal treatment strategies in patients with localized prostate cancer

Several parameters are important in treatment planning among patients with localized PCa, such as life expectancy, comorbidities, performance status, International Society of Urologic Pathologists (ISUP) grading, Tumor-Node-Metastasis (TNM) staging, Gleason score, serum PSA level and PSA velocity.3 Furthermore, according to the major risk indicators, patients are classified into three risk groups to facilitate treatment planning (Figure 1).8

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Irrespective of the risk group, PCa patients with a short life expectancy (less than 10 years) and patients who are medically unfit for local curative treatment are offered “watchful waiting” instead of radical treatment.3 Active surveillance is an option for patients with low risk localized disease and radical treatment could be deferred until there is progression. However, physicians should ensure the patient’s adherence to the follow up protocol and the potential need for further treatment in the future.3

Radical prostatectomy is one of the standard treatment option for localized PCa regardless of the risk category.3,9 Radical prostatectomy approaches include open retropubic, perineal and two laparoscopic approaches: pure and robot-assisted. The choice of the procedure depends on both the patient’s and surgeon’s individual preferences.3

Apart from surgery, external beam radiotherapy (EBRT) is another recognized principal treatment option for patients with localized PCa. Several studies have shown that dose escalation can improve biochemical control in PCa patients regardless of the risk group.10 Intensity-modulated radiotherapy (IMRT) is an advanced form of high-precision radiotherapy that offers a safer approach to dos escalation and allows sparing of adjacent normal tissues, especially those in the rectum and bladder.11 The efficacy and safety of IMRT have been demonstrated in Chinese patients with PCa, showing favorable toxicity profile with <5% severe acute and late gastrointestinal, and genitourinary complications.11

In addition, biological dose escalation through prostate SBRT has improved patient convenience, system capacity and tumor control with decreased cost and side effects.12 Hence, SBRT is considered as an alternative to conventional IMRT in the treatment of PCa.3

ADT alone is no longer considered as a standard treatment for localized PCa. However, in high risk localized PCa patients with planned radiotherapy, ADT is recommended as a neoadjuvant for a period of 4 to 6 months and an adjuvant for 2 to 3 years.3

Additionally, novel agents, such as ARIs, have been introduced into the treatment practice of localized PCa. These agents can be effective in achieving prostatic androgen suppression and have the potential to reduce tumor burden in men with intermediate-to high-risk PCa, but further robust data is needed to consolidate their role in this setting.

Emerging treatment strategies in metastatic prostate cancer

The optimal treatment for metastatic PCa (mPCa) depends on the number and type of bone and lymph node metastases.2 Standard treatment for mPCa is ADT with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, or bilateral orchiectomy. The efficacy of the LHRH agonists or antagonists was proven to be non-inferior to bilateral orchiectomy in mPCa.13 Additionally, survival benefits were comparable between intermittent and continuous ADT.14

The use of ADT has been associated with deleterious effects on bone health. Vitamin D3 and calcium supplements are, therefore, recommended to reduce ADT-associated osteoporosis in patients with mPCa.2 In addition to ADT, combination with chemotherapy or ARIs such as abiraterone, enzalutamide, or apalutamide, should be considered for patients with newly-diagnosed distant metastatic disease, in particular with high metastatic disease burden (4 or more metastasis) or adverse disease features (Gleason score 8 or presence of visceral metastasis).15,16

Apart from systemic treatment, the addition of prostate radiotherapy has been evaluated by two randomized controlled trials in newly diagnosed metastatic hormone-naive PCa.17,18 In a combined cohort of over 2,000 patients, prostate radiotherapy with ADT improved survival (absolute survival benefit of 7% at 3 years) over systemic therapy alone in patients with low metastatic burden but not in high-burden patients.17 Therefore, prostate radiotherapy with ADT is now a recommended first-line option for newly diagnosed men with low metastatic burden PCa.

Castration resistance is a common challenge in mPCa. mCRPC is determined by disease progression despite ADT or castration, as defined by serum testosterone lower than 50ng/dL or 1.7nmol/L. Three consecutive rises in PSA one week apart resulting in 50% increases from baseline (with PSA above 2ng/mL), either two or more new bone lesions on bone scan or a soft tissue lesion using Response Evaluation Criteria in Solid Tumors (RECIST) are regarded as the clinically relevant endpoints to determine as disease progression.2

Without further effective treatment in patients with mCRPC, lethal events would be the ultimate consequences. Nowadays, first-line treatment options for mCRPC are ARIs with abiraterone or enzalutamide, chemotherapy with docetaxel, and alpha-emitting radioisotopes with radium-223.19,20 The two most important factors in selecting the treatment strategy are the presence of symptomatic disease and the response to primary ADT. In mCRPC patients who have progressed despite docetaxel chemotherapy, further treatment options with abiraterone, cabazitaxel, enzalutamide, or radium-223 could be offered.2

Assessment of treatment response in mCRPC patients through regular blood tests (at least 3 times a month), including PSA, alkaline phosphatase and lactate dehydrogenase, are highly recommended.2 Clinical assessment notably symptomatic control, and regular follow-up imaging, e.g. bone scan, CT scan or PSMA-PET scan, is important in determining the disease control.2

Message to the physicians

In Hong Kong, the annual number of new cases of PCa is rising. Excellent survival rates were demonstrated when the disease is diagnosed and treated at the localized stage. Although there is no cure for the advanced metastatic stage of PCa, the latest treatment therapies can help slow the disease progression, maintain quality of life and prolong life.

Conclusion

The advancements in the diagnosis of prostate cancer, e.g. TPUS prostate biopsy and PSMA-PET scan etc., has refined the accuracy in staging of this increasingly prevalent disease in Hong Kong. Localized PCa is highly curable with the contemporary surgical approach or radiotherapy technique, while active surveillance with the purpose of reserving radical treatment till progression might be an option for low risk disease. With the promising efficacy of chemotherapy, novel ARIs, and the prostate radiotherapy, ADT should no longer be considered as the sole treatment for mPCa. Nowadays, the contemporary treatment options have dramatically changed the landscape of mPCa, resulting in long lasting clinical responses with manageable toxicity and preserving quality of life. Collectively, endeavors in clinical research and advanced disease management are now transforming the incurable metastatic conditions into a chronic illness.

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