Abstract Context Overexpression of immune checkpoint molecules affects tumor-specific T-cell immunity in the cancer microenvironment, and can reshape tumor progression and metastasis. Antibodies ...targeting checkpoints could restore antitumor immunity by blocking the inhibitory receptor-ligand interaction. Objective To analyze data and current trends in immune checkpoint targeting therapy for urologic cancers. Evidence acquisition Systematic literature search for clinical trials in the PubMed and Cochrane databases up to August 2014 according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Endpoints included oncologic results, tumor response rates, safety, and tolerability. Evidence synthesis Anti-CTLA-4 monotherapy has demonstrated biochemical responses in prostate cancer. One phase 3 trial assessing ipilimumab efficacy in castration-resistant disease was negative overall. Nevertheless, ipilimumab may significantly improve overall survival compared with placebo in subgroups of patients with favorable prognostic features. In renal cancer, phase 1 trials showed interesting stabilization or long-lasting objective response rates approaching 50% using anti-PD-1/PD-L1 drugs in heavily pretreated metastatic patients. In bladder cancer, one phase 2 trial indicated a good safety profile for ipilimumab as a neoadjuvant drug before radical cystectomy. Overall, immune-related effects such as colitis and dermatitis were common and well tolerated. Conclusions Our systematic review shows that antibodies blocking immune checkpoints offer interesting and long-lasting response rates in heavily pretreated patients with advanced urologic cancers. More promising results are currently provided by anti-CTLA-4 antibodies in prostate cancer and by PD-1/PD-L1 inhibitors in renal cancer. These should encourage new clinical trials of immune therapy combinations and immunotherapy monotherapy combined with conventional anticancer drugs. In bladder cancer, the use of targeted immunotherapy still remains underevaluated; however, preliminary results reported at recent conferences seem encouraging. Patient summary Data from studies support the activity and safety of immune checkpoint inhibitors in urologic cancers, alone or in combination with conventional cancer therapies. Encouraging data in other oncologic fields could translate into interesting responses in urological cancers.
Abstract Context The incidence of muscle invasive bladder cancer (MIBC) increases with age. With increased life expectancy the number of elderly MIBC patients is expected to increase. Existing ...guidelines on management of MIBC do not preclude curative treatments for elderly patients. However, it is necessary to assess the risks and benefits of a treatment to avoid overtreatment that results in decreased health-related quality of life without prolonging survival. Objective To report on overall survival (OS), cancer specific survival (CSS), and morbidity after curative treatment in elderly patients, defined as age >70 yr, with nonmetastatic MIBC and to compare this with the outcome of younger MIBC patients. Evidence acquisition A systematic review was performed using Medline, PubMed, and Embase databases. Articles were included if they addressed one of the three research questions: 1) Does a geriatric assessment improve outcome in elderly patients with MIBC? 2) Do elderly patients have inferior survival, both CSS and OS, after curative therapy compared to younger patients with MIBC? 3) Do elderly patients have an increased complication rate, defined as perioperative mortality (POM) and both early and late complication rate, after curative therapy compared to younger patients with MIBC? Only articles including >100 patients and with a clear age–stratification were included. Evidence synthesis Forty-two articles were retrieved for review. No article directly addressed the use of geriatric assessment. OS and CSS worsen significantly with age both after radical cystectomy and radiotherapy regimens. While POM significantly increases with age, morbidity seems comparable between younger and older patients. Conclusions Although a proportion of elderly patients with MIBC will benefit from curative treatment, we observed worse OS, CSS, and POM with age. The impact of age on late morbidity is less clear. Prospective studies evaluating geriatric assessments are critically needed to optimize MIBC management in the elderly. Patient summary We performed a systematic review to evaluate the outcome and complication rate in elderly patients with muscle invasive bladder cancer. We observed that overall survival and cancer specific survival significantly decrease and perioperative mortality significantly increases with age. The impact of age on late morbidity is less clear. There is a need for geriatric assessments to select those patients that will benefit from curative treatment.
Although magnetic resonance imaging (MRI) is broadly implemented into active surveillance (AS) protocols, data on the reliability of serial MRI in order to help guide follow-up biopsy are ...inconclusive.
To assess the diagnostic estimates of serial prostate MRI for prostate cancer (PCa) progression during AS.
We systematically searched PubMed, Scopus, and Web of Science databases to select studies analyzing the association between changes on serial prostate MRI and PCa progression during AS. We included studies that provided data for MRI progression, which allowed us to calculate diagnostic estimates. We compared Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) accuracy with institution-specific definitions.
We included 15 studies with 2240 patients. Six used PRECISE criteria and nine institution-specific definitions of MRI progression. The pooled PCa progression rate, which included histological progression to Gleason grade ≥2, was 27%. The pooled sensitivity and specificity were 0.59 (95% confidence interval CI 0.44–0.73) and 0.75 (95% CI 0.66–0.84) respectively. There was significant heterogeneity between included studies. Depending on PCa progression prevalence, the pooled negative predictive value for serial prostate MRI ranged from 0.81 (95% CI 0.73–0.88) to 0.88 (95% CI 0.83–0.93) and the pooled positive predictive value ranged from 0.37 (95% CI 0.24–0.54) to 0.50 (95% CI 0.36–0.66). There were no significant differences in the pooled sensitivity (p = 0.37) and specificity (p = 0.74) of PRECISE and institution-specific schemes.
Serial MRI still should not be considered a sole factor for excluding PCa progression during AS, and changes on MRI are not accurate enough to indicate PCa progression. There was a nonsignificant trend toward improved diagnostic estimates of PRECISE recommendations. These findings highlight the need to further define the optimal triggers and timing of biopsy during AS, as well as the need for optimizing the quality, interpretation, and reporting of serial prostate MRI.
Our study suggests that serial prostate magnetic resonance imaging (MRI) alone in patients on active surveillance is not accurate enough to reliably rule out or rule in prostate cancer progression. Other clinical factors and biomarkers along with serial MRI are required to safely tailor the intensity of follow-up biopsies.
Serial prostate magnetic resonance imaging (MRI) in patients on active surveillance is not accurate enough to reliably rule out or rule in prostate cancer progression. Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations offer some improvements in serial MRI assessment; however, at present, other clinical factors along with serial MRI are required to safely tailor active surveillance and follow-up biopsies.
Abstract Context Pelvic lymph node dissection (PLND) in prostate cancer is the most effective method for detecting lymph node metastases. However, a decline in the rate of PLND during radical ...prostatectomy (RP) has been noted. This is likely the result of prostate cancer stage migration in the prostate-specific antigen-screening era, and the introduction of minimally invasive approaches such as robot-assisted radical prostatectomy (RARP). Objective To assess the efficacy, limitations, and complications of PLND during RARP. Evidence acquisition A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1990 to December 2012. The literature search used the following terms: prostate cancer, radical prostatectomy, robot-assisted , and lymph node dissection. Evidence synthesis The median value of nodal yield at PLND during RARP ranged from 3 to 24 nodes. As seen in open and laparoscopic RP series, the lymph node positivity rate increased with the extent of dissection during RARP. Overall, PLND-only related complications are rare. The most frequent complication after PLND is symptomatic pelvic lymphocele, with occurrence ranging from 0% to 8% of cases. The rate of PLND-associated grade 3–4 complications ranged from 0% to 5%. PLND is associated with increased operative time. Available data suggest equivalence of PLND between RARP and other surgical approaches in terms of nodal yield, node positivity, and intraoperative and postoperative complications. Conclusions PLND during RARP can be performed effectively and safely. The overall number of nodes removed, the likelihood of node positivity, and the types and rates of complications of PLND are similar to pure laparoscopic and open retropubic procedures.
Objectives
To evaluate the relationship between metabolic syndrome and the frequency and severity of lower urinary tract symptoms (LUTS).
Patients and Methods
In all, 4666 men aged 55–100 years ...consulting a general practitioner during a 12‐day period in December 2009 have been included in this observational study. LUTS were defined according to the International Prostate Symptom Score (IPSS) and metabolic syndrome with the National Cholesterol Education Program/Adult Treatment Panel III definition. We studied the correlation between metabolic syndrome and its individual components, and the severity of LUTS (IPSS and treatment for LUTS). Analyses were adjusted for body mass index, age, and prostate‐specific antigen level.
Results
Metabolic syndrome was reported in 51.5% of the patients and 47% were treated for LUTS. There was a significant link between metabolic syndrome and treated LUTS (P < 0.001). The risk of being treated for LUTS also increased with an increasing number of metabolic syndrome components present. Metabolic syndrome was positively correlated with the severity of the LUTS (P < 0.001) for overall IPSS and both voiding and storage scores (P < 0.001). Each component of the metabolic syndrome (except high‐density lipoprotein‐cholesterol) appeared as an independent risk factor of high IPSS and of LUTS treatment in multivariate analysis. Metabolic syndrome was positively correlated with prostate volume.
Conclusions
Our results suggest a significant relationship between LUTS linked to benign prostatic hyperplasia and metabolic syndrome, in terms of frequency and severity. The risk of being treated for LUTS also increased with an increasing number of metabolic syndrome components present. The prevention of such modifiable factors by the promotion of dietary changes and regular physical activity practice may be of great importance for public health.
Purpose
Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches ...such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field.
Methods
We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses.
Results
Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet.
Conclusion
Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.
Abstract Context The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that ...low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment. Objective To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa. Evidence acquisition A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer. Evidence synthesis The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score ≤6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume < 0.5 cm3 . Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression. Conclusions The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa.
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