Introduction
This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC).
Materials and methods
PubMed, ...Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS).
Results
We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58–0.95) and better PFS (pooled HR 0.51, 95% CI 0.30–0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55–0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53–1.14).
Conclusion
This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.
Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment ...clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED
®
, Web of Science™, and Scopus
®
databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients’ demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio HR: 3.24, 95% confidence interval CI 2.57–4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42–2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18–8.20), higher neutrophil–lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07–1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52–4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.
A placebo is an inert substance normally used in clinical trials for comparison with an active substance. However, a placebo has been shown to have an effect on its own; commonly known as the placebo ...effect. A placebo is an essential component in the design of conclusive clinical trials but has itself become the focus of intense research. The placebo effect is partly the result of positive expectations of the recipient on the state of health. Conversely, a nocebo effect is when negative expectations from a substance lead to poor treatment outcomes and/or adverse events. Randomized controlled trials in functional urology have demonstrated the importance of the placebo and nocebo effects across different diseases such as overactive bladder, urinary incontinence, lower urinary tract symptoms and interstitial cystitis/painful bladder syndrome, as well as male and female sexual dysfunction. Understanding the true nature of the placebo-nocebo complex and the scope of its effect in functional urology could help urologists to maximize the positive effects of this phenomenon while minimizing its potentially negative effects.
Purpose
The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with ...recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC).
Methods
We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut‐off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut‐off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index).
Results
Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02–1.47,
p
= 0.03), but not with PFS (HR: 0.96, 95% CI 0.65–1.44,
p
= 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00–1.46,
p
= 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model.
Conclusion
Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.
Purpose
To evaluate the potential predictive value of the preoperative serum albumin to globulin ratio (AGR) for oncological outcomes in patients treated with radical prostatectomy (RP) for ...clinically non-metastatic prostate cancer (PCa).
Methods
Pre-operative AGR was assessed in a multi-institutional cohort of 6041 patients treated with RP. Logistic regression analyses were performed to assess the association of the AGR with advanced disease. We performed Cox regression analyses to determine the relationship between AGR and biochemical recurrence (BCR).
Results
The optimal cut-off value was determined to be 1.31 according to receiver operating curve analysis. Compared to patients with a higher AGR, those with a lower preoperative AGR had worse BCR-free survival (
P
< 0.01) in the Kaplan–Meier analysis. Pre- and post-operative multivariable models that adjusted for the effects of established clinicopathologic features, confirmed its independent association with BCR hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31–1.75,
P
< 0.01, HR 1.55, 95% CI 1.34–1.79,
P
< 0.01, respectively. However, the addition of AGR to established prognostic models did not improve their discrimination.
Conclusion
While AGR is significantly associated with BCR, in the present study, the clinical impact of AGR was not large enough to affect patient management. Longer follow-up is necessary to observe the true effect of AGR.
PURPOSE OF REVIEWThe aim of this article is to review incidence, risk factors, and optimal management of de-novo urothelial carcinoma in transplant recipients.
RECENT FINDINGSThere is a two to ...three-fold increased risk for de-novo malignant tumors after solid-organ transplantation, but there is currently no consensus regarding optimal management of de-novo urothelial carcinoma in transplanted patients. Known risk factors include polyomavirus BK, aristolochic acid, and smoking. Data suggest a higher rate of high-grade tumors, as well as predominantly higher stage at primary diagnosis, for both NMIBC and muscle-invasive bladder cancer (MIBC). Treatment for NMIBC includes TURB, mitomycin, and Bacille de Calmette-Guérin instillation with special concern to the immunosuppressive regime. Treatment of MIBC or advanced urothelial carcinoma includes radical cystectomy with chemotherapy if the patient is eligible. A screening should be performed in all transplant recipients, to allow early diagnosis.
SUMMARYDe-novo urothelial carcinoma in transplant recipients is more frequent than in the general population and these tumors were more likely to be high-grade tumors and diagnosed at an advanced stage. There is very little information available on the optimal treatment for these patients. However, aggressive treatment and a strict management according the given recommendations are of the utmost importance.
PURPOSE OF REVIEWThere is heightened awareness and trends towards centralizing high-risk, complex surgeries such as radical cystectomy to minimize complications and improve survival. However, after ...nearly a decade of mandated and/or passive centralization of care, debate regarding its benefits and harms continues.
RECENT FINDINGSDuring the past decade, mandated and passive centralization has led to an increase in radical cystectomies performed in high-volume hospitals (HVHs) and, perhaps by high-volume surgeons (HVS), in addition to efforts to increase the uptake of multidisciplinary strategies in the management of radical cystectomy patients. Consequently, 30 and 90-day mortality rates and overall survival have improved, and major complications and transfusion rates have decreased. Factors impacting surgical quality, such as negative surgical margin(s), pelvic lymphadenectomy and/or lymph node yield rates have increased. However, current studies have not demonstrated a coadditive impact of centralization on oncological outcomes (i.e. cancer-specific and recurrence-free survival). The benefits of centralization on oncologic survival of radical cystectomy remain unclear given the varied definitions of HVHs and HVSs across studies. In fact, centralization of radical cystectomy could lead to an increase in patient load in HVHs and for HVSs, thereby leading to longer surgery waiting times, a factor that is important in the management of muscle-invasive bladder cancer.
SUMMARYThe benefits of centralization of radical cystectomy with multidisciplinary management are shown increasingly and convincingly. More studies are necessary to prospectively test the benefits, risks and harms of centralization.
Background
Current guidelines recommend assessing the prognosis in high-risk upper tract urothelial carcinoma patients (UTUC) after surgery. However, no specific method is endorsed. Among the various ...prognostic models, nomograms represent an easy and accurate tool to predict the individual probability for a specific event. Therefore, identifying the best-suited nomogram for each setting seems of great interest to the patient and provider.
Objectives
To identify, summarize and compare postoperative UTUC nomograms predicting oncologic outcomes. To estimate the overall performance of the nomograms and identify the most reliable predictors. To create a reference tool for postoperative UTUC nomograms, physicians can use in clinical practice.
Design
A systematic review was conducted following the recommendations of Cochrane’s Prognosis Methods Group. Medline and EMBASE databases were searched for studies published before December 2021. Nomograms were grouped according to outcome measurements, the purpose of use, and inclusion and exclusion criteria. Random-effects meta-analyses were performed to estimate nomogram group performance and predictor reliability. Reference tables summarizing the nomograms’ important characteristics were created.
Results
The systematic review identified 26 nomograms. Only four were externally validated. Study heterogeneity was significant, and the overall Risk of Bias (RoB) was high. Nomogram groups predicting overall survival (OS), recurrence-free survival (RFS), and intravesical recurrence (IVR) had moderate discrimination accuracy (c-Index summary estimate with 95% confidence interval 95% CI and prediction interval PI > 0.6). Nomogram groups predicting cancer-specific survival (CSS) had good discrimination accuracy (c-Index summary estimate with 95% CI and PI > 0.7). Advanced pathological tumor stage (≥ pT3) was the most reliable predictor of OS. Pathological tumor stage (≥ pT2), age, and lymphovascular invasion (LVI) were the most reliable predictors of CSS. LVI was the most reliable predictor of RFS.
Conclusions
Despite a moderate to good discrimination accuracy, severe heterogeneity discourages the uninformed use of postoperative prognostic UTUC nomograms. For nomograms to become of value in a generalizable population, future research must invest in external validation and assessment of clinical utility. Meanwhile, this systematic review serves as a reference tool for physicians choosing nomograms based on individual needs.
Systematic Review Registration
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282596
, identifier PROSPERO CRD42021282596.
Purpose
To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa).
Methods
...Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008–2020). Kaplan–Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP).
Results
Median time follow-up was 35 (19–64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5,
p
= 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5,
p
= 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4,
p
= 0.03), relative to their BxPCa counterparts.
Conclusion
AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.
Objectives
Insulin‐like growth factor‐I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly ...investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐2 and ‐3 on outcomes after radical cystectomy.
Methods
A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐2 and ‐3 with outcomes.
Results
On multivariable analysis adjusting for the effects of preoperative variables, lower insulin‐like growth factor‐I binding protein‐2 levels were associated with an increased risk of lymph node metastasis and (any non‐organ confined disease) any non‐organ confined disease. Insulin‐like growth factor‐I binding protein‐3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin‐like growth factor‐I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin‐like growth factor‐I binding protein‐2 and ‐3 plasma levels were associated with recurrence‐free survival, cancer‐specific survival, and overall survival. insulin‐like growth factor‐I binding protein‐2 and ‐3 levels and improved the discrimination of a standard reference model for the prediction of recurrence‐free survival, cancer‐specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively).
Conclusions
Preoperative insulin‐like growth factor‐I binding protein‐2 and ‐3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.
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