Abstract Context Due to the complexity and challenging nature of radical prostatectomy (RP), it is likely that both short- and long-term outcomes strongly depend on the cumulative number of cases ...performed by the surgeon as well as by the hospital. Objective To review systematically the association between hospital and surgeon volume and perioperative, oncologic, and functional outcomes after RP. Evidence acquisition A systematic review of the literature was performed, searching PubMed, Embase, and Scopus databases for original and review articles between January 1, 1995, and December 31, 2011. Inclusion and exclusion criteria comprised RP, hospital and/or surgeon volume reported as a predictor variable, a measurable end point, and a description of multiple hospitals or surgeons. Evidence synthesis Overall 45 publications fulfilled the inclusion criteria, where most data originated from retrospective institutional or population-based cohorts. Studies generally focused on hospital or surgeon volume separately. Although most of these analyses corroborated the impact of increasing volume with better outcomes, some failed to find any significant effect. Studies also differed with respect to the proposed volume cut-off for improved outcomes, as well as the statistical means of evaluating the volume–outcome relationship. Five studies simultaneously compared hospital and surgeon volume, where results suggest that the importance of either hospital or surgeon volume largely depends on the end point of interest. Conclusions Undeniable evidence suggests that increasing volume improves outcomes. Although it would seem reasonable to refer RP patients to high-volume centers, such regionalization may not be entirely practical. As such, the implications of such a shift in practice have yet to be fully determined and warrant further exploration.
Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or ...without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer.
Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored.
Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP.
Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.
There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease.
To examine the efficacy of any form ...of LT±androgen deprivation therapy (ADT) in treating these individuals.
Using the National Cancer Database (2003–2011), we retrospectively identified 2967 individuals who received LT±ADT versus ADT alone for cN1 PCa. Only radical prostatectomy (RP) and radiation therapy (RT) were considered as definitive LT.
LT±ADT versus ADT alone.
Instrumental variable analyses (IVA) were performed using a two-stage residual inclusion approach to compare overall mortality (OM)-free survival between patients who received LT±ADT versus ADT alone. The same methodology was used to further compare OM-free survival between patients who received RP±ADT versus RT±ADT.
Overall, 1987 (67%) and 980 (33%) patients received LT±ADT and ADT alone, respectively. In the LT±ADT group, 751 (37.8%) and 1236 (62.2%) patients received RP±ADT and RT±ADT, respectively. In IVA, LT±ADT was associated with a significant OM-free survival benefit (hazard ratio=0.31, 95% confidence interval CI=0.13–0.74, p=0.007), when compared with ADT alone. At 5 yr, OM-free survival was 78.8% (95% CI: 74.1–83.9%) versus 49.2% (95% CI: 33.9–71.4%) in the LT±ADT versus ADT alone groups. When comparing RP±ADT versus RT±ADT, IVA showed no significant difference in OM-free survival between the two treatment modalities (hazard ratio=0.54, 95% CI=0.19–1.52, p=0.2). Despite the use of an IVA, our study may be limited by residual unmeasured confounding.
Our findings show that PCa patients with clinically pelvic lymph node-positive disease may benefit from any form of LT±ADT over ADT alone. While not necessarily curative by itself, the use of RP or RT could be the first step in a multi-modality approach aiming at providing the best cancer control outcomes for these individuals.
We examined the role of local treatment for clinically pelvic lymph node-positive prostate cancer. We found that the delivery of radical prostatectomy or radiation therapy may be associated with an overall mortality-free survival benefit compared with androgen deprivation therapy alone.
The delivery of local treatment for cN1 prostate cancer may be associated with an overall mortality-free survival benefit compared with androgen deprivation therapy alone, while no difference was found between radical prostatectomy and radiotherapy. These preliminary results warrant further consideration in randomized controlled trials.
Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will ...have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.
In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60–70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.
Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58–67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2–7·5). Most cancers were grade group 2 (79 78% of 101). At 24 months, 78 (88% 95% CI 79–94) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.
24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.
Insightec and the National Cancer Institute.
Objective
To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90‐day postoperative mortality during the index stay and upon readmission.
...Patients and methods
A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90‐day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics.
Results
An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0–9.7%, P < 0.001) and during readmission (2.0–13.1%, P < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac‐ (odds ratio OR 3.1, 95% confidence interval CI 1.9–5.1), pulmonary‐ (OR 4.8, 95% CI 2.8–8.4), and renal‐related (OR 3.6, 95% CI 2–6.7) complications had the most significant impact on the odds of mortality across categories examined.
Conclusions
The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality.
We examined the effect of veteran status on prostate specific antigen (PSA) screening and whether health coverage available to veterans mitigates racial disparities in PSA screening.
We conducted a ...cross-sectional analysis of non-Hispanic White (NHW) and non-Hispanic Black (NHB) men aged between 55 and 69 years who responded to the PSA screening survey in the 2018 Behavioral Risk Factor Surveillance System data. Complex weighted logistic regression models were used to evaluate predictors of PSA screening.
Screening prevalence was 43% in veterans (95% CI 42%-45%) versus 40% in nonveterans (95% CI 39%-40%, p <0.001). Among nonveterans, the prevalence of PSA screening was significantly lower in NHB (34%, 95% CI 31%-37%) versus NHW men (40%, 95% CI 39%-41%, p <0.001). Among veterans, NHB men had a significantly higher screening prevalence (48%, 95% CI 43%-54%) versus NHW men (42%, 95% CI 41%-44%, p=0.04). In adjusted analysis, veteran status (OR 1.11, 95% CI 1.01-1.21, p=0.02) and NHB race (OR 1.29, 95% CI 1.12-1.48, p <0.001) were significantly associated with receipt of PSA screening. Given that we found an interaction between veteran status and race (p
=0.03), a marginal analysis was performed. Compared to NHB nonveterans, NHB veterans had higher odds of undergoing PSA screening (OR 1.46, 95% CI 1.11-1.91, p=0.01). However, this association was not demonstrated when comparing NHW veterans versus nonveterans (OR 1.06, CI 0.97-1.16, p=0.22).
Veteran status and NHB race were found to be independent predictors of PSA screening. The interaction between veteran status and race suggests that access to health coverage available to veterans may mitigate racial differences in prostate cancer screening behaviors. Further studies are needed to translate such findings into the civilian health care system.
Abstract
Background
Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADRs) occur in every organ system, often ...due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes would be reported more frequently in association with ICIs.
Methods
We analyzed VigiBase, the World Health Organization pharmacovigilance database, to identify renal ADRs (rADRs), such as nephritis, nephropathy and vascular disorders, reported in association with ICI therapy. We performed a disproportionality analysis to explore if rADRs were reported at a different rate with one of the ICI drugs compared with rADRs in the entire database, using an empirical Bayes estimator as a significance screen and defining the effect size with a reporting odds ratio (ROR).
Results
We found 2341 rADR for all examined ICI drugs, with a disproportionality signal solely for nephritis ROR = 3.67, 95% confidence interval (CI) 3.34–4.04. Examining the different drugs separately, pembrolizumab, nivolumab and ipilimumab + nivolumab combination therapy had significantly higher reporting odds of nephritis than the other ICI drugs (ROR = 4.54, 95% CI 3.81–5.4; ROR = 3.94, 95% CI 3.40–4.56; ROR 3.59, 95% CI 2.71–4.76, respectively).
Conclusions
Using a pharmacovigilance method, we found increased odds of nephritis when examining rADRs associated with ICI therapy. Pembrolizumab, nivolumab and a combination of ipilimumab + nivolumab showed the highest odds. Clinicians should consider these findings and be aware of the increased risk of nephritis, especially in patients treated with pembrolizumab, when administering ICI therapy.
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