Search

Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population. An analysis of the first 753 metastatic castration-resistant prostate cancer (mCRPC) patients within ePAD demonstrated that 43% were aged 75 years and older. Older patients were more likely to have comorbidities including ischemic heart disease, diabetes and previous stroke. Treatment outcomes were similar in all age groups. However, older patients receiving chemotherapy were more likely to stop treatment due to toxicity. Furthermore, in a smaller ePAD analysis involving additional chart reviews within 3 high volume centres, at least one relative or absolute contraindication to abiraterone was seen in 72% of our cohort and with enzalutamide in 14%. In total, 47% had potential clinically significant drug interactions with abiraterone and 67% with enzalutamide. Registry-based randomised controlled trials (RRCTs) are a novel trial methodology aiming to bridge the gap between retrospective registry analyses and traditional randomised controlled trials. We conducted the REAL-Pro study in advanced prostate cancer, comparing cognition, depression and falls risk between CRPC patients receiving abiraterone or enzalutamide. The study closed early due to slow recruitment and a changing treatment landscape, highlighting the need for further research to understand clinician and patient perspectives towards pragmatic trials such as RRCTs and subsequently develop strategies to optimise future trial design and recruitment. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has demonstrated limited activity in prostate cancer to date. This likely reflects an immune suppressive tumor microenvironment (TME), with previous studies suggesting low PD-L1 expression and a sparse immune cell infiltrate. We aimed to further characterise the immune TME in primary prostate cancer and correlate immune subset densities with clinical outcomes. Methods: Two distinct cohorts of patients treated with radical prostatectomy were identified, based on the development of biochemical recurrence (BCR), one subgroup with high International Society of Urological Pathologists (ISUP) grade group, recurrent disease and a second with low grade, non-recurrent disease. A prostate immunohistochemical (IHC) antibody cocktail was used to differentiate tumor and peritumoral benign tissue. Specific CD8+, CD4+, FoxP3+, CD20+ and CD68+ cell subsets were identified using IHC staining of consecutive slides. PD-L1 and CD8/PD-L1 dual staining were also performed. Cell subset densities were quantified within tumor and peritumoral regions. We used descriptive statistics to report cell subset densities and T-tests to compare groups by age, grade and the development of BCR. Univariable and multivariable logistic regression were used to analyse risk factors for BCR and the development of metastatic disease. Results: A total of 175 patients were included, with a median age of 63 years and median pre-operative PSA of 8.2ng/ml. BCR occurred in 115 patients (66%) and 56 (32%) developed metastatic disease. CD68+ cells were the most abundant (median 648.8/mm2 intratumoral, 247.6/mm2 peritumoral), while PD-L1+ and PD-L1/CD8+ cell density was low overall (PD-L1+ median 162.4/mm2 intratumoral, 141.7/mm2 peritumoral; PD-L1/CD8+ (median 5.52/mm2 intratumoral, 3.41/mm2 peritumoral). Overall, grade group and T-stage were independently associated with BCR and metastatic disease. Higher density of peritumoral PD-L1+ cells was an independent risk factor for BCR (OR 5.33, 95%CI 1.31–21.61, p = 0.019).Although higher densities of CD8+ and CD4+ cells were observed in higher grade group 3–5 tumors, these were not associated with the development of BCR or metastasis. Conclusions: In our cohort of prostate cancer patients who underwent radical prostatectomy, higher grade group and T-stage were independent predictors of BCR and metastasis. Despite higher grade group being associated with higher CD8+ cell density, PD-L1+ and PD-L1/CD8+ cell densities were low overall, suggesting lower T cell receptor recognition of tumor antigens. Further understanding of this phenomenon would influence development of future immunotherapeutic strategies in prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen positron emission tomography-computed tomography use prior to systemic therapy in metastatic castration-resistant prostate cancer Abbreviations (m)CRPC (metastatic) castration-resistant prostate cancer ePAD electronic Prostate Cancer Australian Database FDG fluorodeoxyglucose HSPC hormone-sensitive prostate cancer LN lymph nodes PET positron emission tomography PSMA prostate-specific membrane antigen WBBS whole-body bone scan Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-CT imaging has demonstrated greater sensitivity compared to conventional imaging modalities with CT and whole-body bone scan (WBBS) in the detection of metastatic prostate cancer [[1]]. A further 15 patients (17%) had dedicated CT alone in addition to PSMA PET-CT, while eight (9%) had additional WBBS alone in addition to PSMA PET-CT (Fig. [Extracted from the article]

Health economic outcomes of real-world treatment sequencing of androgen receptor-targeted agents (ARTA) and docetaxel (DOC) remain unclear. Data from the electronic Castration-resistant Prostate cancer Australian Database (ePAD) were analyzed including median overall survival (mOS) and median time-to-treatment failure (mTTF). Mean total costs (mTC) and incremental cost-effectiveness ratios (ICER) of treatment sequences were estimated using the average sample method and Zhao and Tian estimator. Of 752 men, 441 received ARTA, 194 DOC, and 175 both sequentially. Of participants treated with both, first-line DOC followed by ARTA was the more common sequence (n = 125, 71%). mOS for first-line ARTA was 8.38 years (95% CI: 3.48, not-estimated) vs. 3.29 years (95% CI: 2.92, 4.02) for DOC. mTTF was 15.7 months (95% CI: 14.2, 23.7) for the ARTA-DOC sequence and 18.2 months (95% CI: 16.2, 23.2) for DOC-ARTA. In first-line, ARTA cost an additional $13,244 per mTTF month compared to DOC. In second-line, ARTA cost $6726 per mTTF month. The DOC-ARTA sequence saved $2139 per mTTF compared to ARTA-DOC, though not statistically significant. ICERs show ARTA had improved clinical benefit compared to DOC but at higher cost. There were no significant cost differences between combined sequences. [ABSTRACT FROM AUTHOR]

The authors comment on a study by N. Sayegh and colleagues published within the issue which highlighted the advances in the therapeutic armamentarium of advanced prostate cancer. Topics include importance of addressing the barriers to treatment access in the global management of metastatic prostate cancer, importance of the role of multidisciplinary team in ensuring a holistic approach to overall patient care, and role of specialist nurses in support patients.

Aim: Optimal treatment for newly diagnosed metastatic hormone‐sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D‐ADT). This study sought to define the therapy used and associated activity following D‐ADT. Methods: Retrospective analysis of patients with mHSPC treated with one or more cycles of D‐ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first‐line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate‐specific antigen (PSA) reduction >50% and time from 1L to second‐line (2L) treatment initiation. Results: A total of 93 patients received D‐ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9–16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9–7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second‐line treatment was 7.3 months (1.3–27.4), which did not differ significantly between treatment groups. Conclusions: Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D‐ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D‐ADT needed. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusion International practice guidelines recommend administration of bone‐modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal‐related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear.To describe real‐world practice of Australian breast oncologists.Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)‐Positive Australian Patient (TABITHA), a multi‐site Australian HER2+ MBC registry.Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32–87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first‐line systemic anti‐HER2 therapy (95% vs 83%; P = 0.04), to present with bone‐only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4‐weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data.Three‐quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence. [ABSTRACT FROM AUTHOR]