King’s Health Partners’ Prostate Cancer Biobank (KHP PCaBB)

Prostate cancer affects approximately 1.1 million men worldwide [1], yet much remains unknown about this complex disease. The heterogeneous nature of prostate cancer makes it difficult to elucidate the specific mechanisms of disease aetiology and progression. As such, urological biobanking aims to provide a resource to bridge this gap through the translation of research into practical applications, thereby spurring advancements in both public health and personal patient care [2].

Currently, more than 12 prostate biorepositories in the UK have been established for current or prospective research such as ProtecT, ProMPT and the Wales Cancer Bank [3]. While all biobanks record clinical information of disease, few include the demographic characteristics of donors; leaving pockets of unexplored territory in prostate cancer research.

King’s Health Partners (KHP) sees nearly 20,000 suspected cancer patients each year, drawn from a referral base of over two million people across South East London (Fig. 1) and treats approximately 6500 cancer patients [4]. Because of its outreach, patients referred to KHP have a wide ethnic and socioeconomic diversity, hence its biobanks are a valuable and often unique resource for medical research of various diseases, including prostate cancer. The KHP Prostate Cancer Biobank (KHP PCaBB) was established in 2013 as part of the KHP Cancer Biobank and recruit donors from the Urology or Oncology Departments at Guy’s Hospital. Patients may be approached to give their consent for biobanking at any point in their treatment pathway (Fig. 2), which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. As such, the KHP PCaBB consists of patients who gave consent for biobanking after 1 January 2013, but whose samples may have been collected before that date. Prostate cancer patients are currently asked to donate samples of blood and surplus prostate tissue as well as permitting access to their data. Clinical data continues to be added throughout the course of their disease.

A recent audit of the KHP Prostate Cancer Biobank revealed that between 2013 to 2015, 1796 patients were diagnosed with prostate cancer at KHP and 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had given consent compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy’s and St Thomas’ NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity and socioeconomic status (Table 1). Greater differences were observed in clinical characteristics, with treatment type differing significantly between the patients who had given consent and total patient population (Table 2).

The KHP PCaBB is both a clinically and demographically representative database; therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.

All cohort descriptions presented below are based on the 549 patients who gave consent between January 2013 and December 2015 (Tables 1 and 2). Recruitment to the Biobank is ongoing (Fig. 3).

The KHP PCaBB is both a clinically and demographically representative database – making it an ideal platform for research in the field of prostate cancer. The multi-ethnic foundation of our patient population grants our biobank the potential to contribute to investigations on aetiological and pathophysiological differences in prostate cancer between various ethnic groups, especially amongst UK residents of Black descent [12]. Furthermore, the clinical diversity of our repository makes it possible to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.

The following are examples to highlight the possible areas where KHP PCaBB can contribute to prostate cancer research:

Afro-Caribbean men are three times more likely to develop prostate cancer than white men [13] and, are more likely to present with aggressive, higher-stage disease [14]. There are several hypotheses that surround this observation, one of which attributes this difference to reduced expression of Duffy antigen/receptor for chemokines (DARC) on the red blood cells of Black men. DARC is commonly expressed in Caucasians while approximately 95% of endemic African populations lack its expression [15].

DARC acts as a malaria parasite receptor. As such, in many African countries where malaria is fairly common, the lack of DARC expression in these populations may have resulted from an evolutionary selection process that favoured resistance towards malarial infection [15]. However, the DARC protein does confer beneficial effects – most notably, by sequestering key angiogenic chemokines including IL-8, Gro- alpha 1, MCP-1 and RANTEs from blood, thereby preventing prostate tumour development and progression [15]. Theoretically reduced expression of DARC may result in increased risk of prostate cancer incidence and severity.

In an ongoing study by Galustian and colleagues, blood samples from 100 white men and 60 black men with a diagnosis of prostate cancer were supplied by the KHP PCaBB to investigate genotypic characteristics of DARC status as well as the corresponding levels of chemokines to identify its association to cancer severity (Galustian et al., unpublished).

A renewed interest in cancer immunotherapy over the past years has resulted in significant breakthroughs for patients with various tumour types, resulting in new systemic cancer treatments translating into true survival benefits. Although immunotherapy is currently not considered a standard treatment for advanced prostate cancer, there is a substantial body of evidence suggesting that prostate cancer is immunogenic. The Hayday laboratory at King’s College London recently showed that the body harbours a natural mechanism, termed Lymphoid Stress-Surveillance (LSS), which displays a high level of inter-individual variation and could underpin heterogeneity in immune-mediate tumour surveillance [16]. There is evidence to suggest that this rapid LSS mechanism plays an important role in prostate cancer development and progression [17, 18]. However, the status of LSS in human prostate cancer remains largely unexplored.

By using blood samples in a longitudinal study, the Hayday group is examining peripheral immune responses of prostate cancer patients undergoing treatment at KHP [19]. LSS profiles of various prostate cancer patients are being investigated including the following cohorts: ‘High Risk’ (n = 25) and ‘Low Risk’ (n = 25) localised prostate cancer, ‘Post Prostatectomy’ (n = 25) and patients with advanced prostate cancer receiving abiraterone acetate (n = 15) and docetaxel (n = 15). Patterns of LSS are currently being investigated to predict individual PCa-specific mortality and responses to treatments.

Data collected for the KHP PCaBB constructs a comprehensive demographic and clinical profile of each prostate cancer patient who has given consent for biobanking. The KHP PCaBB has thereby amassed a rich data and tissue repository that is largely reflective of both the demographic and clinical diversity within the total prostate cancer patient population seen at KHP, however this is not reflected by the various prostate cancer treatment types as surgical patients represented more than half of biobank participants.