• Gene: BRCA1&2, the mutations that occur in these genes is associated with hereditary prostate cancer and an increased risk of developing aggressive forms of the disease

Therapeutic target protein:

• Protein: Androgen receptor (AR). The overexpression of AR is a therapeutic target for prostate cancer treatment and is associate

Epidemiology and Disparities

The epidemiology in prostate cancer reveals significant trends in incidence and mortality rates as follows:

• Incidents and Mortality rates

Most common solid organ malignancy in US

Black men experience higher risk compared to any other racial & ethnic groups

Black men face a disproportionately higher mortality rate

• Disparities affecting black men

They face a higher incidence of prostate cancer

mortality rate for black men are approx double

There is ongoing research into screening practices and access to care

Also looking at treatment considerations for black men

• Ongoing investigations and considerations

To address the disparities affecting black men

Screening aims to enhance early detection and intervention

Advanced Prostate Cancer Management Updates

American Urological Association/Society of Urologic Oncology (AUA/SUO) guidelines on:

Biochemical recurrence without metastatic disease

the revised guidelines provide updated recommendations on pationts who:

• experience rising prostate-specific antigen (PSA) levels after failure of local therapy

• Does not present with demonstrateble metastatic disease through conventional imaging

The treatment options available are observation or clinical trial enrolment or systemic treatments that would impact treatment-related adverse events and the patients quality of life

The introduction of advanced imaging modalities such as Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET) allows for:

• Enhanced sensitivity and specificity in the detection of metastatic diseases

• Updates that have influenced the approach to managing patients with rising PSA levels post-local therapy

Metastatic hormone-sensitive prostate cancer (mHSPC)

The prognosis assessment and treatment recomendations are based on:

• The extent of metastatic disease in newly diagnosed mHSPC patients

• The role of PSMA PET imaging in this assessment

• The utilisation of androgen deprivation therapy (ADT) in combination with androgen pathway-directed therapy

• Chemo, based on recent clinical trials and evidence

Non-metastatic castration-resistant prostate cancer (nmCRPC)

Role of PSMA PET imaging:

• Used for monitoring the disease status of men with nmCRPC

• It enhances sensitivity and accuracy in detecting potential metastatic lesions

• It has more precise disease monitoring and treatment planning

Impact of PSADT

• PSA doubling time (PSADT) in assessing disease progression

• Identifies high risk patients

Recommendations for imaging intervals

• For there to be regular imaging evaluations for men with nmCRPC

• The integration of PSMA PET imaging-disease monitoring and the potential for early detection of metastatic progression

Metastatic castration-resistant prostate cancer (mCRPC)

The updated guidelines emphasise the necessity for annual imaging in mCRPC patients without PSA progression or new symptoms

They introduce the potential use of 177Lu-PSMA-617 in the context of progressive mCRPC, based on positive PSMA PET imaging study and its impact on patient outcomes

Significance of PET imaging:

• advanced molecular imaging technique used in the evaluation of prostate cancer

• utilises PET in combination with a radiotracer

• Targets the PSMA

• It has influence the diagnosis and management of advanced prostate cancer

Guidelines that support PSMA PET imaging speak about how:

• It identifies metastatic sites not previously detected with conventional imaging

• There are potential implications of such findings in patient outcomes and therapeutic decisions

Therapeutic decision making and Systematic updates

mHSPC and mCRPC have evidence-based recommendations for therapeutic decision-making

Recommendations encompass:

• Androgen receptor pathway inhibitors

• Chemotherapy

• Novel agents such as 177Lu-PSMA-617

Therapeutic decision-making in mHSPC and mCRPC

Evidence based guidelines prove clear recommendations that:

• For mHSPC, the guidelines emphasise that the use of ADT in combination with either androgen pathway-directed therapy, abiraterone acetate plus prednisone, apalutamide, or enzalutamide

• The evidence on chemotherapy supports the significant extension of overall survival and progression-free survival in mHSPC patients

In mCRPC - ADT with abiraterone acetate plus prednisone, docetaxel, or

enzalutamide

 Additionally, the novel agent 177Lu-PSMA-617 - particularly those with progressive

disease following prior treatments

The inclusion of 177Lu-PSMA-617 in the guidelines reflects the evolving landscape of

therapeutic options for advanced prostate cancer.

Role of Biomarkers and other systemic therapies

•To identify DNA repair deficiencies

• To have microsatelite instability (MSI) status

• To see tumour mutational burden has gained prominence

The guidelines explore the potential importance of germline and somati tuour testing by predicting responses to PARP inhibitors such as olaparib, rucaparib, and niraparib

PARP inhibitors target DNA replication machinary

• Has promising outcomes in tumours with deficienciesin homologous recombination repair, such as those with BRCA1 or BRCA2 mutations

The guidelines explore the potential of immunotherapies in the management of advanced prostate cancer.

• The treatments generally show less efficacy in prostate cancer compared to other malignancies due to the relatively low tumour mutational burden of most prostate cancers

Unmet Needs and Future Directions

Management of prostate cancer continues to face various unmet needs

 Disparities in outcomes, the demand for personalized care, and the exploration of the optimal

sequencing of therapies

Disparities in Outcomes and Personalized Care

 Subpopulations such as Black patients

 Understanding the societal and biological factors contributing to these disparities

• Ensure equitable access to high-quality care and improved outcomes

Demand for personalized care

 Predictive markers for treatment selection based on tumour and host biology

Personalized care can enable tailored treatment approaches

 Individual patient characteristics