Management of patients with advanced prostate cancer in the Asia Pacific region: 'real-world' consideration of results from the Advanced Prostate Cancer Consensus Conference (APCCC) 2017.

OBJECTIVE: The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real-world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017). FINDINGS: Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration-naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor-targeting agents appear to be well tolerated in Asian men with metastatic castration-resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision-making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower-income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side-effect profiles of some drugs and influence prescribing. CONCLUSIONS: As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team-based approach to treatment planning and care, delivery of best-practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.

Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. METHODS: Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Multiparametric MRI maps for detection and grading of dominant prostate tumors.

PURPOSE: To develop an image-based technique capable of detection and grading of prostate cancer, which combines features extracted from multiparametric MRI into a single parameter map of cancer probability. MATERIALS AND METHODS: A combination of features extracted from diffusion tensor MRI and dynamic contrast enhanced MRI was used to characterize biopsy samples from 29 patients. Support vector machines were used to separate the cancerous samples from normal biopsy samples and to compute a measure of cancer probability, presented in the form of a cancer colormap. The classification results were compared with the biopsy results and the classifier was tuned to provide the largest area under the receiver operating characteristic (ROC) curve. Based solely on the tuning of the classifier on the biopsy data, cancer colormaps were also created for whole-mount histopathology slices from four radical prostatectomy patients. RESULTS: An area under ROC curve of 0.96 was obtained on the biopsy dataset and was validated by a "leave-one-patient-out" procedure. The proposed measure of cancer probability shows a positive correlation with Gleason score. The cancer colormaps created for the histopathology patients do display the dominant tumors. The colormap accuracy increases with measured tumor area and Gleason score. CONCLUSION: Dynamic contrast enhanced imaging and diffusion tensor imaging, when used within the framework of supervised classification, can play a role in characterizing prostate cancer.

Managing advanced prostate cancer in the Asia Pacific region: "Real-world" application of Advanced Prostate Cancer Consensus Conference 2019 statements.

AIM: The second Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) gathered insights into the real-world application in the Asia-Pacific (APAC) region of consensus statements from the 3rd Advanced Prostate Cancer Consensus Conference (APCCC 2019). METHODS: The 4-h our virtual meeting in October 2020 brought together 26 experts from 14 APAC countries to discuss APCCC 2019 recommendations. Presentations were prerecorded and viewed prior to the meeting. A postmeeting survey gathered views on current practice. RESULTS: The meeting and survey highlighted several developments since APAC APCCC 2018. Increased access and use in the region of PSMA PET/CT imaging is providing additional diagnostic and staging information for advanced prostate cancer and influencing local and systemic therapy choices. Awareness of oligometastatic disease, although not clearly defined, is increasing. Novel androgen receptor pathway antagonists are expanding treatment options. Cost and access to contemporary treatments and technologies continue to be a significant factor influencing therapeutic decisions in the region. With treatment options increasing, multidisciplinary treatment planning, shared decision making, and informed choice remain critical. A discussion on the COVID-19 pandemic highlighted challenges for diagnosis, treatment, and clinical trials and new service delivery models that will continue beyond the pandemic. CONCLUSION: APAC-specific prostate cancer research and data are important to ensure that treatment guidelines and recommendations reflect local populations and resources. Facilitated approaches to collaboration across the region such as that achieved through APAC APCCC meetings continue to be a valuable mechanism to ensure the relevance of consensus guidelines within the region.

Measurement of serum PSA as a predictor of symptoms scored on the IPSS for patients with benign prostatic hyperplasia.

OBJECTIVES: To investigate if serum PSA levels would correlate with patients' symptoms. Serum prostate-specific antigen (PSA) levels correlate to size of the prostate gland. Prostate gland size has a direct correlation to the symptoms experienced by patients. PATIENTS AND METHODS: A retrospective analysis of cross-sectional data collected on levels of serum PSA and symptom scores using the International Prostate Symptom Score (IPSS) collected from males who attended the prostate clinic in Christchurch Public Hospital with a diagnosis of benign prostatic hyperplasia (BPH) in the period of January 2007 to January 2012. A total of 833 subjects were found and a Pearson product moment correlation analysis (r value) and a coefficient of determination (R2 value) was calculated to compare PSA levels versus symptom scores. RESULTS: PSA compared to IPSS showed a mild trend with a r-value of 0.1375 (p=0.00003): showing a mild statistically significant correlation between these two parameters. However R2 value was only 0.0189 meaning each unit increase of serum PSA only influences 1.89% of the change in the symptom score. PSA vs QoL scores, there was a mild correlation found with the r-value of 0.207 (p=0.00001). However the R2 value was only 0.043, showing only a mild 4.3% influence by PSA on quality of life. CONCLUSION: PSA would not be a good predictor for symptom scores and hence it is unable to accurately gauge the symptomatic severity in BPH patients.

Infection-related hospital admissions after transrectal biopsy of the prostate.

BACKGROUND: Urosepsis is the most common complication requiring hospital admission after transrectal biopsy of the prostate. This study aims to assess the local incidence and causative organisms of hospital admissions with urosepsis after transrectal ultrasound-guided prostate (TRUS) biopsy. As morbidity is high, treatment must be commenced empirically prior to cultures. A review of bacterial antibiotic susceptibilities was undertaken to guide optimal treatment of post-biopsy urosepsis. METHODS: A total of 1421 patients underwent TRUS biopsy in a single city over a 2-year period. All patients received prophylactic antibiotics prior to the procedure. A retrospective review of a prospectively collated database was performed in all patients admitted to Christchurch Hospital, the only acute admitting hospital in Christchurch, with infection within 30 days after biopsy. Hospital admission records were reviewed, including urine and blood culture results. RESULTS: Forty patients (2.8%) were admitted with infection after the biopsy, the majority occurring within the first week after procedure and four required intensive care unit (ICU) admission (10%). The most common organism isolated on urine and blood cultures was Escherichia coli. Significant E. coli resistance was seen to fluoroquinolones, amoxicillin and trimethoprim. CONCLUSION: Rates of infection after TRUS biopsy and antibiotic resistance are increasing internationally. Treatment for urosepsis should be aggressive as 10% of those patients admitted required ICU admission. TRUS biopsy with ciprofloxacin prophylaxis led to infectious complications comparable with other international reports and appears to remain an appropriate prophylactic antibiotic of choice. Infections requiring hospital admission were all susceptible to a combination of ceftriaxone and gentamicin, and would be an effective initial antibiotic of choice.

Radical prostatectomy for high-risk clinically localized prostate cancer: a prospective single institution series.

OBJECTIVE: The objective of this paper is to report on the pathologic and biochemical progression-free outcomes of patients who underwent radical prostatectomy for high-risk localized prostate cancer. METHODS: Data was collected prospectively from 299 patients who underwent radical prostatectomy for high-risk clinically localized prostate cancer by 2 surgeons at a single institution. High risk was defined as 1 or more of 3 adverse factors: prostate-specific antigen (PSA) >20, biopsy Gleason score 8 to 10 and clinical stage T3. PSA recurrence was defined as PSA >0.4 ng/mL or any salvage therapy. RESULTS: Median age was 63.3 years (46.1-75.9). Median follow-up was 4.7 years (range 0.5-17.3 years). PSA at diagnosis was >20 ng/mL in 31.4%. Biopsy Gleason score was 8 to 10 in 66.9%. Clinical stage was T3 in 24.4%. 81.6% of patients had a single baseline risk factor, 15.7% had 2 risk factors and 2.7% had all 3 risk factors. Neoadjuvant therapy was administered to 184 patients (61.5%). Pathologic stage was organ-confined in 39.6%, specimen-confined in 26%, non-specimen-confined in 26.4%, and 8% had lymph node positive disease. Overall survival, cancer-specific survival and biochemical progression-free survival was 99%, 99.67% and 70.2%, respectively. Univariate analysis showed that PSA at diagnosis, percentage of cores positive and number of risk factors were predictors of PSA recurrence (p < 0.05). Multivariate analysis showed that PSA at diagnosis was an independent predictor of PSA recurrence (p < 0.05). CONCLUSION: Radical prostatectomy is associated with favourable biochemical progression-free, clinical and overall survival in selected men with high-risk localized prostate cancer, and should therefore be considered an option in these patients. Baseline PSA >20 ng/mL is a significant independent predictor of PSA recurrence.

Intermittent androgen suppression for prostate cancer.

Although androgen deprivation therapy (ADT) has been a cornerstone of the management of prostate cancer for more than 50 years, controversy remains regarding its optimum application. Intermittent androgen suppression (IAS) has been researched since the mid-1980s as a way of reducing the adverse effects and cost of continuous androgen suppression. With preclinical evidence suggesting a potential benefit in terms of time to androgen independence, IAS has been the focus of a number of clinical phase II and III trials. Overall, these trials suggest that IAS is neither inferior nor superior to continuous androgen suppression, with respect to time to castration resistance and cancer-specific survival, but has significant advantages in terms of adverse effects, quality of life and cost. A number of unresolved questions remain, however, including how to select patients for therapy, the optimum duration of therapy, when to restart therapy after the off cycle, and how to define progression to castration-resistant disease. Landmark randomized clinical trials comparing IAS to continuous androgen suppression are in progress and will hopefully answer many of these questions. In future, the use of second-line drugs in the off-treatment phase holds potential for delaying disease progression in men on IAS. At present, men with advanced disease who are deemed candidates for ADT should be informed of IAS as a treatment option, considered experimental from an informed consent point of view, but promising based on current evidence.