Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

Comparison of contemporary methods for estimating prostate tumour volume in pathological specimens.

OBJECTIVE: To evaluate the accuracy of various prostate tumour volume (TV) estimation methods. To determine the most appropriate estimation method for current clinical practice. PATIENTS AND METHODS: Radical prostatectomy (RP) specimens from multiple institutions were analysed by a single uro-pathologist between September 2009 and May 2011. Tumour properties including thickness, width and length were collected and TV was established using computer-assisted image analysis (CAIA). TV estimation methods including; square, cuboidal and ellipsoidal estimations were calculated using previously reported formulae. The estimation methods were compared against the 'gold-standard' and the accuracy of identifying clinically significant tumours of TV ≥0.5 cc was determined. RESULTS: In all, 299 consecutive specimens were analysed by a single uropathologist. The median index TV on CAIA was 1.42 cc. Of the four estimation methods, the ellipsoid methods produced the closest correlation with the gold-standard (r(2) 0.91, P = 0.71). This correlation lost accuracy when larger tumours (TV >4 cc) were excluded from the analysis (r(2) = 0.73, P = 0.003). Sensitivity and specificity for identifying clinically significant tumours was 94% and 92% respectively, when using the ellipsoid estimation. CONCLUSIONS: In current uro-pathology, the ellipsoidal estimation method appears to be the most suitable for estimating TV in prostate cancers. This method is cheap, reproducible and sensitive and can be safely used as a surrogate for CAIA volumes when such technology is not available.

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer.

BACKGROUND AND OBJECTIVE: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer. METHODS: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA. KEY FINDINGS AND LIMITATIONS: PSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when managed with androgen deprivation therapy for biochemical recurrence (adjusted hazard ratio [AHR] 0.54 [0.34-0.87]; n = 174). PSMA low tumors possess molecular markers of resistance to radiotherapy. Consistent with this, patients with high PSMA tumors experience longer time to recurrence following primary radiotherapy (AHR 0.50 [0.28-0.90]; n = 248). In the SAKK09/10 trial (n = 224), patients with high PSMA tumors who were managed with salvage radiotherapy experienced longer time to progression in the 64-Gy arm (restricted mean survival time [RMST] +7.60 [0.05-15.16]), but this effect was mitigated in the 70-Gy arm (RMST 3.52 [-3.30 to 10.33]). Limitations include using PSMA RNA as a surrogate for PET SUVmax. CONCLUSIONS AND CLINICAL IMPLICATIONS: PSMA levels in treatment-naïve prostate cancer differentiate tumor biology and treatment susceptibilities. These results warrant validation using PET metrics to substantiate management decisions based on imaging.

Incorporating VR-RENDER Fusion Software in Robot-Assisted Partial Prostatectomy: The First Case Report.

Currently, the active surveillance of men with favorable intermediate-risk localized prostate cancer (PCa) is a longstanding controversy, in terms of their oncological outcomes, and radical prostatectomy would constitute a similar concern of overtreatment, regarding its functional outcomes. Thus, focal therapy could be considered in men belonging to favorable intermediate-risk group. Among all focal therapies, high-intensity focused ultrasound (HIFU) was the most studied methodology in clinical trials. Although HIFU provided better functional outcomes than radical prostatecomy, the oncological outcomes were inferior in men with intermediate-risk localized PCa. Two articles have been published discussing the feasibility and clinical outcomes of robot-assisted partial prostatectomy (RAPP), and both the functional and oncological outcomes were superior than those with HIFU. However, the rate of positive surgical margins (PSMs) was reported as high in the literature. Here, we present a case of favorable intermediate-risk localized PCa with an isolated tumor at the anterior apex. After reconstructing a personal three-dimensional (3D) image, we utilized it in a 3D image-guided precise excise, followed by intraoperative frozen specimen review. We found that this method may present a resolution to the high PSM rate documented in the current literature regarding RAPP. This method merits further study with a well-designed prospective study.

More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer.

BACKGROUND: The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. OBJECTIVE: The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. DESIGN, SETTING, AND PARTICIPANTS: We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. RESULTS AND LIMITATIONS: The average number of RLNs was 20.8 (median: 19; interquartile range: 14-25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p=0.02). Other predictors of CSM were Gleason score 8-10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p ≤ 0.006). The study is limited by its retrospective nature. CONCLUSIONS: In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. PATIENT SUMMARY: We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

Predicting survival of patients with node-positive prostate cancer following multimodal treatment.

BACKGROUND: According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes. OBJECTIVE: To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)-free rate in pN1 patients. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated. RESULTS AND LIMITATIONS: All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p=0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5-83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature. CONCLUSIONS: Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.

Survival following biochemical recurrence after radical prostatectomy and adjuvant radiotherapy in patients with prostate cancer: the impact of competing causes of mortality and patient stratification.

BACKGROUND: Data regarding the natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) and adjuvant radiotherapy (aRT) are limited. OBJECTIVE: To evaluate cancer-specific (CSM) and other-cause mortality (OCM) in prostate cancer patients with BCR after RP and aRT. DESIGN, SETTING, AND PARTICIPANTS: We identified 336 patients with BCR treated between 1990 and 2006 at two tertiary care centers. INTERVENTION: All patients underwent RP plus aRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression analyses were used to evaluate the association between clinicopathologic variables and CSM. The coefficients of CSM-independent predictors were used to develop a novel nomogram. Patients were stratified into groups according to nomogram-calculated CSM probability and median age. Competing-risks survival analyses were used to estimate CSM and OCM for each group. RESULTS AND LIMITATIONS: Ten-year CSM and OCM were 21.5 and 21.7%, respectively. On multivariable analyses, short time to BCR, pathologic Gleason score ≥ 8, and positive lymph node count of more than two at RP were significantly associated with increased CSM rate (all p ≤ 0.01). These variables were used to develop a novel nomogram, which was used to stratify patients according to their 10-yr, nomogram-calculated, CSM probability: ≤ 10% versus >10-30% versus >30%. On competing-risks analysis, 10-yr CSM rate for these groups was 6%, 15%, and 42%, respectively, for patients aged ≤ 68 yr, versus 8%, 19%, and 42% for patients aged >68 yr. Likewise, 10-yr OCM rate was 24%, 9%, and 10%, respectively, for patients aged ≤ 68 yr, versus 37%, 20%, and 28%, respectively, for patients aged >68 yr. The study is limited by its retrospective design. CONCLUSIONS: Short time to BCR, pathologic Gleason score ≥ 8, and more than two positive lymph nodes were independent predictors of CSM in patients with BCR after RP and aRT. Men with these features may benefit from additional secondary therapies, ideally, in a clinical trial setting.

Magnetic resonance imaging/ultrasound-fusion biopsy significantly upgrades prostate cancer versus systematic 12-core transrectal ultrasound biopsy.

BACKGROUND: Gleason scores from standard, 12-core prostate biopsies are upgraded historically in 25-33% of patients. Multiparametric prostate magnetic resonance imaging (MP-MRI) with ultrasound (US)-targeted fusion biopsy may better sample the true gland pathology. OBJECTIVE: The rate of Gleason score upgrading from an MRI/US-fusion-guided prostate-biopsy platform is compared with a standard 12-core biopsy regimen alone. DESIGN, SETTING, AND PARTICIPANTS: There were 582 subjects enrolled from August 2007 through August 2012 in a prospective trial comparing systematic, extended 12-core transrectal ultrasound biopsies to targeted MRI/US-fusion-guided prostate biopsies performed during the same biopsy session. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The highest Gleason score from each biopsy method was compared. INTERVENTIONS: An MRI/US-fusion-guided platform with electromagnetic tracking was used for the performance of the fusion-guided biopsies. RESULTS AND LIMITATIONS: A diagnosis of prostate cancer (PCa) was made in 315 (54%) of the patients. Addition of targeted biopsy led to Gleason upgrading in 81 (32%) cases. Targeted biopsy detected 67% more Gleason ≥4+3 tumors than 12-core biopsy alone and missed 36% of Gleason ≤3+4 tumors, thus mitigating the detection of lower-grade disease. Conversely, 12-core biopsy led to upgrading in 67 (26%) cases over targeted biopsy alone but only detected 8% more Gleason ≥4+3 tumors. On multivariate analysis, MP-MRI suspicion was associated with Gleason score upgrading in the targeted lesions (p<0.001). The main limitation of this study was that definitive pathology from radical prostatectomy was not available. CONCLUSIONS: MRI/US-fusion-guided biopsy upgrades and detects PCa of higher Gleason score in 32% of patients compared with traditional 12-core biopsy alone. Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors.