External validation of genomic classifier based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer

Introduction & Objectives: A genomic classifier-based risk stratification nomogram to identify candidates for adjuvant radiation therapy (aRT) after radical prostatectomy (RP) has been proposed (ref: Dalela et al. JCO). Validation study for this model is still lacking. The aim of our study was to externally validate the aforementioned nomogram using a contemporary cohort of men treated with robot-assisted RP. Materials & Methods: A total of 350 patients who underwent RARP, (2013-2018), had adverse pathology features (positive margin,and/or pT3a/b). Genomic profile data was available for all these men. The decision and the timing to administer aRT, and androgen deprivation therapy was based on patient life expectancy, treatment expectations, and PSA kinetics. The metastasis-free survival (MFS) was estimated using the Kaplan-Meier method. The external validity of the nomogram was tested using the concordance index, calibration plot, and decision curve analysis. Results: Median (IQR) follow-up was 26.5 (17.48-36.44) Months. 19.6% had Gleason score ≥8. Non-confined disease (pT3a/b) was noted in 67.61% of the cohort. Overall,14% (49/350) of the patients received aRT. 3.4% of the patients (12/350) developed metastasis. Overall 3-year MFS was 0.95% (95%CI: 0.92 – 0.98). The c-index of the nomogram was 0.837, with favorable calibration characteristics. DCA showed a positive net benefit for probabilities range between a 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model, and 0 for treating all the patients. Conclusions: Our findings corroborate the validity of this genomic based risk-stratification tool using a contemporary cohort in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether or not administer aRT is worthwhile

Role of robot-assisted radical prostatectomy in the management of high-risk prostate cancer

We aimed to evaluate the role of robot-assisted radical prostatectomy (RARP) in the management of high-risk prostate cancer (PCa), with a focus on oncological, functional and perioperative outcomes. Further, we also aimed to briefly describe our novel modification to conventional RARP that allows immediate organ retrieval and examination for intra-operative surgical margin assessment. A literature search of PubMed was performed for articles on the management of high-risk PCa. Papers written in English and concerning clinical outcomes following RARP for locally advanced and high-risk PCa were selected. Outcomes data from our own center were also included. A total of 10 contemporary series were evaluated. Biopsy Gleason score ≥ 8 was the most common cause for classification of patients into the high-risk PCa group. Biochemical failure rate, in the few series that looked at long-term follow-up, varied from 9% to 26% at 1 year. The positive surgical margin rate varied from 12% to 53.3%. Urinary continence rates varied from 78% to 92% at 1 year. The overall complication rates varied from 2.4% to 30%, with anastomotic leak and lymphocele being the most common complications. Long-term data on oncological control following RARP in high-risk patients is lacking. Short-term oncological outcomes and functional outcomes are equivalent to open radical prostatectomy (RP). Safety outcomes are better in patients undergoing RARP when compared with open RP. Improved tools for predicting the presence of organ-confined disease (OCD) are available. High-risk patients with OCD would be ideal candidates for RARP and would benefit most from surgery alone

Variation in prostate cancer care at commission on cancer designated facilities

INTRODUCTION & OBJECTIVES: Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the impact of Commission on Cancer facility type and the single facility on prostate cancer treatment patterns is unknown. MATERIAL & METHODS: We used the National Cancer Data Base between 2004 and 2013 to identify men diagnosed with loco-regional prostate cancer. The cohort was stratified based on the National Comprehensive Cancer Network prostate cancer risk-classes. Cochran-Armitage tests evaluated temporal trends. Random effects hierarchical logit models assessed treatment variation at Commission on Cancer-facility and institution level. RESULTS: In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk-groups between 2004-2013 (p\u3c0.0001). Observation for low-risk prostate cancer increased from 16.3% in 2004-2005 to 32.0% in 2012-2013 (p\u3c0.0001). Significant treatment variation was observed based on Commission on Cancer-facility type. for all riskgroups, rates of treatment according to facility type ranged from 28.4% to 76.9% for radical prostatectomy, 3.6% to 16.2% for brachytherapy, 13.7% to 28.1% for external beam radiation therapy, 1.3% to 7.3% for androgen deprivation therapy, 4.6% to 19.1% for observation, and 0% to 2.1% for cryotherapy. The highest rates of observation for low-risk disease were observed in academic centers. After adjusting for sociodemographic and facility factors, the highest proportions of treatment variation attributable to the single institution were observed for cryotherapy (59%, 95%CI 0.45-0.73) and brachytherapy (46%, 95%CI 38-53%), while the lowest proportion of treatment variation was observed for androgen deprivation therapy (14%, 95%CI 12-15%), and Observation (15%, 95%CI 14-17%). The results were consistent in the sensitivity analysis and in all National Comprehensive Cancer Network risk-groups. CONCLUSIONS: The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions. Policy makers should address these variations to harmonize prostate cancer treatment

Survival associated with radical prostatectomy versus radiotherapy for high-risk prostate cancer: A contemporary, nationwide observational analysis

INTRODUCTION & OBJECTIVES: The optimal primary treatment for men with clinically high-risk prostate cancer (PCa) is controversial as both radical prostatectomy (RP) and radiotherapy (RT) are associated with potential advantages and disadvantages. Our objective was to compare the overall mortality-free survival of high-risk PCa patients treated with primary RP vs. primary RT with neoadjuvant/adjuvant androgen deprivation therapy [ADT], within the National Cancer Data Base (NCDB). MATERIAL & METHODS: Within the NCDB, a total of 87,875 high-risk PCa patients fulfilled our prespecified inclusion criteria (53,197 in RP group and 34,678 in RT+ADT group). We employed an instrumental variable analysis (IVA) approach using the yearly rate of RP as the instrument, to mitigate the impact of both observed and unobserved confounders. Multiple sensitivity analyses were performed, including stratification for age, comorbidity, ADT utilization and high dose (\u3e75.6 Gy) RT. In addition, the overall mortality-free survival of RP was compared to that of RT reported in three recently published randomized controlled trails (RCTs), after selecting only RP patients who fitted inclusion/exclusion criteria of these RCTs RESULTS: On IVA adjusting for socio-demographic, facility- and tumor-specific covariates, RP was associated with lower overall mortality compared to RT+ADT (hazard ratio (HR) 0.52; 95% CI, 0.47-0.57; p\u3c0.001) in the overall analysis, in patients with age ≤65 years with CCI 0 (HR 0.48; p\u3c0.001), in patients \u3e65 years with CCI 0 (0.53; p\u3c0.001), those receiving RT with neoadjuvant (HR 0.52; p\u3c0.001) or adjuvant ADT (HR 0.47; p\u3c0.001), or treated with high dose (≥75.6 Gy) RT (HR 0.54; p\u3c0.001). While the survival outcomes for patients treated with RT (+/-ADT) in the RCTs were not statistically different from similarly treated and appropriately selected patients within the NCDB, RP was associated with greater overall mortality-free survival than any of the arms represented in the RCTs. CONCLUSIONS: Our results suggest that in patients with clinically high-risk PCa, primary RP is associated with greater overall mortality-free survival than primary RT+ADT in patients with clinically high-risk PCa, regardless of baseline characteristics. These findings, in lieu of a randomized trial, can guide the clinicians to carefully choose the primary modality of treatment for patients with high-risk PCa

Variation in locoregional prostate cancer care and treatment trends at commission on cancer designated facilities: a national cancer data base analysis 2004 to 2013.

BACKGROUND: Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the effect of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. PATIENTS AND METHODS: We used the National Cancer Data Base to identify men diagnosed with prostate cancer, between 2004 and 2013. Our cohort was stratified on the basis of the National Comprehensive Cancer Network prostate cancer risk classes. Cochran-Armitage tests were used to evaluate temporal trends. Random effects hierarchical logit models were used to assess treatment variation at Commission on Cancer facility and institution level. RESULTS: In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk groups between 2004 and 2013 (P \u3c .0001). Observation for low-risk prostate cancer increased from 16.3% in 2004 to 2005 to 32.0% in 2012 to 2013 (P \u3c .0001). Significant treatment variation was observed on the basis of Commission on Cancer facility type. Across all risk groups, the lowest rates of radical prostatectomy and highest rates of external beam radiation therapy were observed in community cancer programs. The highest rates of observation for low-risk disease were observed in academic centers. Treatment variation according to institution ranged from 14% (95% confidence interval, 0.12-0.15) for androgen deprivation therapy up to 59% (95% confidence interval, 0.45-0.73) for cryotherapy. CONCLUSION: The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions

Predicting lymph node invasion in patients treated with robot-assisted radical prostatectomy.

INTRODUCTION: To develop a nomogram to predict lymph node invasion (LNI) in the contemporary North American patient treated with robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We included 2,007 patients treated with RARP and pelvic lymph node dissection (PLND) at a single institution between 2008 and 2012. D\u27Amico low risk patients underwent an obturator and hypogastric PLND, while extended PLND was reserved for intermediate/high risk patients. Logistic regression analysis tested the relationship between LNI and all available predictors. Independent predictors of LNI were used to develop a novel nomogram. Discrimination, calibration and decision-curve analysis were used to analyze the performance of our novel nomogram, and compare it to open radical prostatectomy (ORP)-based models, namely the Godoy nomogram. RESULTS: Overall, 5.3% of our patients harbored LNI. Median number of lymph nodes removed was 6.0 (interquartile range: 4-11). The most parsimonious multivariable model to predict LNI consisted of the following independent predictors: PSA value, clinical stage, and primary and secondary Gleason scores (all p ≤ 0.02). The discrimination of our novel model was 86.2%, and its calibration was virtually optimal. Using a 2% nomogram cut off, 58% of patients would be spared PLND, while missing only 9.4% of individuals with LNI. The novel nomogram compared favorably to the Godoy nomogram, when discrimination, calibration and net-benefit were used as benchmarks. CONCLUSIONS: Approximately 5% of contemporary North American patients harbor LNI at RARP. Our novel nomogram can accurately identify these patients, and this may help to improve patient selection, and avoid unnecessary PLND in the majority of patients