Defining the challenges and opportunities for using patient-derived models in prostate cancer research.

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.

Treatment of primary cancer in metastatic hormone-sensitive prostate cancer.

PURPOSE OF REVIEW: Recently, there has been emerging interest in the treatment of primary tumours in metastatic prostate cancer based on major trials that have provided evidence for radiation therapy and cytoreductive radical prostatectomy. Preclinical studies have further established the molecular features of metastatic disease that provide a rationale for primary treatment. RECENT FINDINGS: Several randomised controlled trials and other prospective studies have demonstrated a benefit in overall survival, predominantly in low-volume disease. Advancements in precision medicine also offer insight into improving selection, staging and monitoring. SUMMARY: In this review, the authors highlight and review recent data on emerging and established treatment options and shift towards personalised medicine for hormone-sensitive metastatic prostate cancer.

The role of localised prostate cancer treatment in renal transplant patients: A systematic review.

Objective: To systematically review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients. Method: A systematic review was conducted adhering to PRISMA guidelines. Searches were performed in the Cochrane Library, Embase, Medline, the Transplant Library and Trip database for studies published up to September 2022. Risk of bias was assessed with the Cochrane Risk of Bias in Non-Randomised Studies of Interventions for non-randomised studies tool. Results: A total of 60 studies were identified describing 525 patients. The majority of studies were either retrospective non-randomised comparative or case series/reports of poor quality. The vast majority of studies were focussed on prostate cancer after renal transplantation. Overall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (high-intensity frequency ultrasound) and 21 patients were placed on active surveillance. The mean age was 61 years old, the mean PSA level at diagnosis was 9.6 ng/mL and the mean follow-up time was 31 months. The majority of patients had low-risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%). All prostate cancer mortality cases were in high-risk prostate cancer (≥Gleason 8). The cancer-specific survival results were similar between surgery and radiotherapy at 1 and 3 years. Conclusion: Localised prostate cancer treatment in renal transplant patients should be risk stratified. Surgery and radiation treatment for localised prostate cancer in renal transplant patients appear equally efficacious. Given the limitations of this study, future research should concentrate on developing a multicentre RCT with long-term registry follow-up.

Modified Supine Percutaneous Nephrolithotomy in the Elderly: Outcomes and Safety.

With increases in the aging population, conditions affecting older people and relevant surgical techniques are becoming more pertinent. Modified supine percutaneous nephrolithotomy (PCNL) is increasingly being adopted. There are limited data on the safety of this position in the elderly patient population. We describe our experience of the modified supine position in patients aged 70 years and older. Between April 2011 and March 2021, patients aged 70 years and older undergoing a modified supine PCNL performed by a single surgeon were prospectively evaluated. Data including patient age, operative time, complications, stone clearance, and length of stay were collected and analysed. Sixty-nine procedures were performed on 67 patients with a mean age was 76.5 years. Median total operative time was 95 min with 20 (29%) patients having a combined procedure with ureterorenoscopy. Preoperative mean stone burden was 23.5 mm and complete stone clearance was achieved in 46 (66.7%) patients. Twelve (17.4%) patients had complications during their hospitalisation. Six were Clavien-Dindo class II or less and one Clavien-Dindo class V. The modified supine position for PCNL is safe in the elderly patient population and has advantages including reduced handling of patients and achieving adequate stone-free rates. These benefits are particularly important in the elderly population, which frequently has a reduced tolerance to adaptation.

Can 68 Ga-PSMA positron emission tomography and multiparametric MRI guide treatment for biochemical recurrence after radical prostatectomy?

OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) and Gallium-68 (68 Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in guiding salvage therapy for patients with biochemical recurrence (BCR) post-radical prostatectomy. PATIENTS AND METHODS: Patients were evaluated with paired mpMRI and 68 Ga-PSMA PET/CT scans for BCR (prostate-specific antigen [PSA] >0.2 ng/mL). Patient, tumour, PSA and imaging characteristics were analysed with descriptive statistics. RESULTS: A total of 117 patients underwent paired scans to investigate BCR, of whom 53.0% (62/117) had detectable lesions on initial scans and 47.0% (55/117) did not. Of those without detectable lesions, 8/55 patients proceeded to immediate salvage radiotherapy (sRT) and 47/55 were observed. Of patients with negative imaging who were initially observed, 46.8% (22/47) did not reach threshold for repeat imaging, while 53.2% were rescanned due to rising PSA levels. Of these rescanned patients, 31.9% (15/47) were spared sRT due to proven distant disease, or due to absence of disease on repeat imaging. Of the original 117 patients, 53 (45.3%) were spared early sRT due to absence of disease on imaging or presence of distant disease, while those undergoing delayed sRT still maintained good PSA responses. Of note, patients with high-risk features who underwent sRT despite negative imaging demonstrated satisfactory PSA responses to sRT. Study limitations include the observational design and absence of cause-specific or overall survival data. CONCLUSION: Our findings support the use of mpMRI and 68 Ga-PSMA PET/CT in guiding timing and necessity of salvage therapy tailored to detected lesions, with potential to reduce unnecessary sRT-related morbidity. Larger or randomized trials are warranted to validate this.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

Prostate-specific antigen testing for prostate cancer: Time to reconsider the approach to screening.

BACKGROUND: Prostate cancer is now the most common cancer in men in Australia. Men should be aware of the potential risk of significant prostate cancer despite the lack of symptoms. Screening for prostate cancer using prostate-specific antigen (PSA) has been controversial. General practice guidelines can be confusing leading to men not being tested for prostate cancer. Reasons cited include overdiagnosis and overtreatment with associated morbidity. OBJECTIVE: This article aims to highlight the current evidence for PSA testing and advocate for updating outdated guidelines and resources. DISCUSSION: Current evidence shows that a risk-stratified approach to PSA screening helps to assess that risk. Recent studies show improved survival rates with early intervention compared with observation/delayed treatment. Imaging, including magnetic resonance imaging and prostate-specific membrane antigen positron emission tomography, have made a significant difference in the management pathway. Biopsy techniques have progressed to minimise sepsis risk. Quality and patient-reported outcomes registry data highlight the increased use of active surveillance in patients with low to intermediate risk of prostate cancer, reducing treatment-associated harms in men with low risk of progression. There have also been improvements in medical therapeutics for advanced disease.

Patterns of chemotherapy use in muscle-invasive bladder cancer in a tertiary centre.

Objectives: Although neoadjuvant chemotherapy (NAC) has been demonstrated to have significant benefits to survival in patients with muscle-invasive bladder cancer (MIBC), the current utilization of NAC in Australia is unknown. The aim of this study was to evaluate the patterns of neoadjuvant and adjuvant chemotherapy (AC) use in patients undergoing cystectomy for MIBC at a large tertiary institution in Australia. Methods: A retrospective study was conducted using data of patients who underwent a radical cystectomy (RC) at a high-volume centre for MIBC between 2011 and 2021. Results: Of 69 patients who had a cystectomy for ≥ pT2 bladder cancer, 73.9% were eligible for NAC. However, of those eligible, only five patients received NAC (9.8%). Of the total patients who were eligible for AC, only 44.4% received postoperative chemotherapy. Common reasons for the lack of uptake were due to patients being unfit or declining treatment. There was no difference in progression-free survival or overall survival in those who received NAC and AC. Conclusions: The majority of patients undergoing RC for MIBC received AC compared to NAC, reflecting the real-world challenge of NAC uptake. This highlights the need for ongoing improvements in selection and usage of NAC and less reliance of AC utilization post RC.

Defining Diagnostic Criteria for Prostatic Ductal Adenocarcinoma at Multiparametric MRI.

Background Prostatic ductal adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer that often warrants multimodal therapy and poses a significant diagnostic challenge clinically and at imaging. Purpose To develop multiparametric MRI criteria to define DAC and to assess their diagnostic performance in differentiating DAC from prostatic acinar adenocarcinoma (PAC). Materials and Methods Men with histologically proven DAC who had multiparametric MRI before radical prostatectomy were retrospectively identified from January 2011 through November 2018. MRI features were predefined using a subset of nine DACs and then compared for men with peripheral-zone DACs 1 cm or greater in size and men with matched biopsy-confirmed International Society of Urological Pathology grade group 4-5 PAC, by four independent radiologists blinded to the pathologic diagnosis. Diagnostic performance was determined by consensus read. Patient and tumor characteristics were compared by using the Fisher test, t-tests, and Mann-Whitney U test. Agreement (Cohen κ) and sensitivity analyses were also performed. Results There were 59 men with DAC (median age, 63 years [interquartile range, 56, 67 years]) and 59 men with PAC (median age, 64 years [interquartile range, 59, 69 years]). Predefined MRI features, including intermediate T2 signal, well-defined margin, lobulation, and hypointense rim, were detected in a higher proportion of DACs than PACs (76% [45 of 59] vs 5% [three of 59]; P < .001). On consensus reading, the presence of three or more features demonstrated 76% sensitivity, 94% specificity, 94% positive predictive value [PPV], and 80% negative predictive value [NPV] for all DACs and 100% sensitivity, 95% specificity, 81% PPV, and 100% NPV for pure DACs. The DACs and PACs showed no difference in contrast enhancement (100% vs 100%; P >.99, median T2 signal intensity (254 vs 230; P = .99), or apparent diffusion coefficient (median, 677 10-6 mm2/sec vs 685 10-6 mm2/sec; P = .73). Conclusion The presence of intermediate T2 signal, well-defined margin, lobulation, and/or hypointense rim, together with restricted diffusion and contrast enhancement at multiparametric MRI of the prostate, suggests prostatic ductal adenocarcinoma rather than prostatic acinar adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article.

Optimizing the diagnosis and management of ductal prostate cancer.

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.

Oncologic outcomes among Black and White men with grade group 4 or 5 (Gleason score 8-10) prostate cancer treated primarily by radical prostatectomy.

BACKGROUND: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis. CONCLUSIONS: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.

Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies.

BACKGROUND: Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC). OBJECTIVE: To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC. DESIGN, SETTING, AND PARTICIPANTS: A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models. RESULTS AND LIMITATIONS: A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation. CONCLUSIONS: Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed. PATIENT SUMMARY: This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.

Long-term renal functional outcomes following ureteroureterostomy performed during multi-organ resection for non-urothelial cancers.

Objectives: To evaluate the long-term renal function outcomes after ureteroureterostomy (UU) in patients undergoing multi-organ resection for non-urothelial cancers. The secondary aim was to examine the length of ureteric defect that can be successfully bridged with UU. Patients and methods: We retrospectively reviewed the charts of patients who underwent UU between 1995 and 2012 at our institution. Renal imaging studies performed before and after UU were used to determine whether hydronephrosis was present. Renal function was assessed by comparing estimated glomerular filtration rate (eGFR) before and at the last follow-up after UU. Results: Nineteen patients underwent UU during multi-organ resection for non-urothelial cancers. Median follow-up time was 62 months. Overall, UU had a high success rate, with one patient (5.2%) developing progressive hydronephrosis with a >20% drop in eGFR from baseline due to UU failure. Four additional patients developed progressive hydronephrosis due to cancer recurrence involving the UU. There were no statistically significant differences between pre- and post-UU eGFR in these patient cohort. All patients with a ureteric defect of ≤5 cm underwent successful reconstruction. Conclusions: UU maintains long-term renal function in the majority of patients undergoing multi-organ resection for non-urothelial cancers and can be successfully utilized if the resected ureteric length is ≤5 cm.

The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin.

OBJECTIVES: To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette-Guérin (BCG) in a contemporary cohort. PATIENTS AND METHODS: We performed an Institutional Review Board-approved database review to identify patients with non-muscle-invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors. RESULTS: A total of 579 patients (median follow-up 4.6 years) received BCG induction for NMIBC; 90% had high-grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and ß-blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes. CONCLUSION: Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.

Cancer in Lockdown: Impact of the COVID-19 Pandemic on Patients with Cancer.

The lockdown measures of the ongoing COVID-19 pandemic have disengaged patients with cancer from formal health care settings, leading to an increased use of social media platforms to address unmet needs and expectations. Although remote health technologies have addressed some of the medical needs, the emotional and mental well-being of these patients remain underexplored and underreported. We used a validated artificial intelligence framework to conduct a comprehensive real-time analysis of two data sets of 2,469,822 tweets and 21,800 discussions by patients with cancer during this pandemic. Lung and breast cancer are most prominently discussed, and the most concerns were expressed regarding delayed diagnosis, cancellations, missed treatments, and weakened immunity. All patients expressed significant negative sentiment, with fear being the predominant emotion. Even as some lockdown measures ease, it is crucial that patients with cancer are engaged using social media platforms for real-time identification of issues and the provision of informational and emotional support.

Patterns of metastases of prostatic ductal adenocarcinoma.

BACKGROUND: The current study was conducted to investigate the patterns of metastases in men with metastatic prostatic ductal adenocarcinoma (DAC) and recurrence patterns after therapy. METHODS: All patients with a new diagnosis of DAC with de novo metastases and those with localized disease who developed metastases after treatment and were treated at the study institution from January 2005 to November 2018 were included. All patient and tumor characteristics and outcome data were collected. RESULTS: A total of 164 patients (37.7%) had metastatic DAC, including 112 with de novo metastases and 52 who developed metastases after treatment. Men with de novo metastases were found to have a significantly higher median prostate-specific antigen level and International Society of Urological Pathology grade but a lower cT3 and/or T4 classification compared with those with metastases that developed after treatment (all P < .05). Approximately 87% of men with de novo metastases progressed despite multiple systemic therapies, 37.6% required intervention for the palliation of symptoms, and 10.1% responded to systemic therapy and underwent treatment of the primary tumor. Men with de novo metastatic DAC and those who developed metastases after treatment had multiple metastatic sites (including bone and viscera), with higher rates of lung metastases noted in the posttreatment group (23.2% vs 44.2%; P = .01). A total of 45 patients who were treated with curative intent developed metastases at a median of 22 months (range, 0.9-74.8 months) after treatment, at low prostate-specific antigen levels (median, 4.4 ng/mL [interquartile range, 1.7-11.1 ng/mL]). CONCLUSIONS: The current study described the metastatic patterns of DAC in both patients with de novo metastatic disease and those who later progress to metastases. Men receiving treatment for DAC with curative intent require stringent long-term follow-up with imaging modalities, including chest imaging given the predilection toward lung metastases noted among these patients.

Downgrading from Biopsy Grade Group 4 Prostate Cancer in Patients Undergoing Radical Prostatectomy for High or Very High Risk Prostate Cancer.

PURPOSE: We examined rates of Grade Group 4 downgrading at radical prostatectomy among men diagnosed with high and very high risk prostate cancer at biopsy. MATERIALS AND METHODS: A pooled cohort of 1,776 patients from 3 tertiary referral centers who underwent radical prostatectomy for National Comprehensive Cancer Network® high risk (prostate specific antigen greater than 20 ng/ml, or Grade Group 4-5, or clinical stage T3 or greater) or very high risk (primary Gleason pattern 5, or more than 4 biopsy cores with Grade Group 4-5, or 2 or more high risk features) disease from 2005 to 2015 were reviewed. Overall 893 patients with Grade Group 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to Grade Group 3 or less at radical prostatectomy. RESULTS: Overall 333 (45%) cases were downgraded to Grade Group 3 or less at radical prostatectomy. Of these cases 198 (27%) had concordant Grade Group 4 biopsy and radical prostatectomy pathology and 195 (27%) were upgraded at radical prostatectomy to Grade Group 5. Of high risk cases with biopsy Grade Group 4 disease 49% had any downgrading vs 29% of very high risk cases (p <0.0001). Downgrading to Grade Group 2 or less occurred in 16% (98 of 604) of high risk and 7% (8 of 122) of very high risk cases (p <0.01). Downgraded cases had a lower prostate specific antigen, fewer positive biopsy cores and lower clinical stage (p <0.01). On multivariable analysis fewer positive biopsy cores were significantly associated with downgrading at radical prostatectomy (p <0.01). CONCLUSIONS: In this cohort of patients with high risk/very high risk prostate cancer, downgrading from biopsy Grade Group 4 at radical prostatectomy occurred less frequently than in other published reports. Any downgrading was significantly less common in very high risk compared to high risk patients, and downgrading to Grade Group 2 or less occurred in a minority of cases in high risk and very high risk patients.

Can online support groups address psychological morbidity of cancer patients? An artificial intelligence based investigation of prostate cancer trajectories.

BACKGROUND: Online Cancer Support Groups (OCSG) are becoming an increasingly vital source of information, experiences and empowerment for patients with cancer. Despite significant contributions to physical, psychological and emotional wellbeing of patients, OCSG are yet to be formally recognised and used in multidisciplinary cancer support programs. This study highlights the opportunity of using Artificial Intelligence (AI) in OCSG to address psychological morbidity, with supporting empirical evidence from prostate cancer (PCa) patients. METHODS: A validated framework of AI techniques and Natural Language Processing (NLP) methods, was used to investigate PCa patient activities based on conversations in ten international OCSG (18,496 patients- 277,805 conversations). The specific focus was on activities that indicate psychological morbidity; the reasons for joining OCSG, deep emotions and the variation from joining through to milestones in the cancer trajectory. Comparative analyses were conducted using t-tests, One-way ANOVA and Tukey-Kramer post-hoc analysis. FINDINGS: PCa patients joined OCSG at four key phases of psychological distress; diagnosis, treatment, side-effects, and recurrence, the majority group was 'treatment' (61.72%). The four groups varied in expression of the intense emotional burden of cancer. The 'side-effects' group expressed increased negative emotions during the first month compared to other groups (p<0.01). A comparison of pre-treatment vs post-treatment emotions showed that joining pre-treatment had significantly lower negative emotions after 12-months compared to post-treatment (p<0.05). Long-term deep emotion analysis reveals that all groups except 'recurrence' improved in emotional wellbeing. CONCLUSION: This is the first empirical study of psychological morbidity and deep emotions expressed by men with a new diagnosis of cancer, using AI. PCa patients joining pre-treatment had improved emotions, and long-term participation in OCSG led to an increase in emotional wellbeing, indicating a decrease in psychological distress. It is opportune to further investigate AI in OCSG for early psychological intervention as an adjunct to conventional intervention programs.

The cytoreductive prostatectomy in metastatic prostate cancer: what the individual trials are hoping to answer.

OBJECTIVE: To review the ongoing randomised trials of cytoreductive prostatectomy (CRP) in de novo hormone-sensitive metastatic prostate cancer (HSPC) in order to identify their goals and assess their strengths and weaknesses. METHODS: PubMed, MEDLINE and clinical trials websites searches were performed to identify currently ongoing trials of CRP in de novo HSPC. RESULTS: Nine randomised clinical trials in CRP were identified and included: Southwest Oncology Group (SWOG) 1802, Surgery in Metastatic Carcinoma of Prostate (SIMCAP), Adjuvant Treatments to the Local Tumour for Metastatic Prostate Cancer: Assessment of Novel Treatment Algorithms (IP2-ATLANTA), Testing Radical prostatectomy in men with prostate cancer and oligoMetastases to the bone (TRoMbone), Impact of Radical Prostatectomy as Primary Treatment in Patients with Prostate Cancer with Limited Bone Metastases (g-RAMPP), Cytoreductive Prostatectomy vs Cytoreductive Prostate Irradiation as a Local Treatment Option for Metastatic Prostate Cancer: a Multicentric Feasibility Trial (LoMP II), Androgen-Deprivation Therapy or Androgen-Deprivation Therapy Plus Definitive Treatment (Radiation or Surgery) (FUSCC-OMPCa), and the Testing Radical Prostatectomy in Chinese Men with Prostate Cancer and oligoMetastases to the Bone study. Each study was different; assessing various primary outcome measures including overall survival (OS), progression-free survival and feasibility to randomise between standard therapy and CRP or between radiation therapy and CRP in the metastatic setting. In the oligometastatic setting, the trials assess OS, feasibility to randomise and time to castration resistance. Similarly, a number of secondary endpoints ranging from cancer-specific outcomes to quality-of-life outcomes are being investigated. The inclusion criteria in these trials also varied in terms of volume of metastatic disease (oligometastatic to high-volume metastatic disease), diagnosis of metastases (imaging based vs biopsy confirmed), imaging modalities used (conventional to newer modalities), as well as outcomes and follow-up regimes. CONCLUSION: While there are differences in each protocol, each trial aims to address different aspects of CRP in de novo HSPC. Therefore, the specific goals of each study and the limitations have to be taken into consideration when interpreting the results of these trials.