Efficacy,Predictive Factors,and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen–ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy

Recently, ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA)–ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1 ng/ml were included. The ⁶⁸Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2–0.5 ng/ml) and low (>0.5–1.0 ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT ≥ 3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive ⁶⁸Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice.

Is an Initial Saturation Prostate Biopsy Scheme Better than an Extended Scheme for Detection of Prostate Cancer? A Systematic Review and Meta-analysis

Context

The optimal initial prostate biopsy core number is still an issue with many unanswered questions and significant controversy.

Objective

To compare diagnostic values of initial saturation prostate biopsy scheme and extended scheme with respect to prostate-specific antigen (PSA) levels, prostate volume (PV), and PSA density (PSAD).

Evidence acquisition

Electronic databases including Medline, Web of Knowledge, and the Cochrane Library were searched through November 1, 2012. Experts were consulted, and references from relevant articles were scanned. The meta-analysis was conducted with RevMan 5.1, according to the PRISMA guidelines. Mantel-Haenszel estimates were calculated and pooled under a fixed or random effect model, with data expressed as risk difference (RD) and 95% confidence interval (CI).

Evidence synthesis

We analyzed eight trials with a total of 11 997 participants who underwent transrectal ultrasound guided prostate biopsies for the first time and met inclusion criteria. Studies consisted of one paired design study, two randomized clinical trials, and five nonrandomized studies. Saturation biopsy scheme showed a significant advantage in prostate cancer (PCa) detection over an extended scheme (RD: 0.04; 95% CI, 0.01–0.08; p = 0.02). In addition, subgroup analyses found a saturation protocol to be superior to an extended protocol in the detection of PCa in men with PSA <10 ng/ml (RD: 0.04; 95% CI, 0.01–0.07; p = 0.002), PV >40 ml (RD: 0.05; 95%CI, 0.01–0.09; p = 0.02), or PSAD <0.25 ng/ml per gram (RD: 0.04; 95% CI, 0.00–0.09; p = 0.04).

Conclusions

The existing evidence indicates that an initial saturation biopsy scheme is more efficient than an extended scheme for PCa detection, especially for those men with lower PSA levels, higher PV, or lower PSAD, without increasing complications and the amount of insignificant cancer.     

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

Context

Randomized clinical trials have recently examined the benefit of adding docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naïve advanced prostate cancer (PCa).

Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Skeletal Metastases from Lung Cancer? A Systematic Review and Network Meta-analysis

BackgroundLung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer.Questions/purposesWe aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution.MethodsWe conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I² value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution.ResultsFor overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2).ConclusionIn this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research.Level of EvidenceLevel I, therapeutic study.     

Does Local Treatment of the Prostate in Advanced and/or Lymph Node Metastatic Disease Improve Efficacy of Androgen-Deprivation Therapy? A Systematic Review

Context

Androgen-deprivation therapy (ADT) plays a pivotal role in the management of locally advanced and metastatic prostate cancer (PCa). When and for how long to apply ADT have remained controversial issues.

Objective

To review randomised studies of ADT (orchiectomy or luteinising hormone-releasing hormone analogues) in PCa—both immediate and deferred/adjuvant studies—to elucidate a possible interaction between local treatment and ADT.

Evidence acquisition

Published randomised studies on ADT in various stages of PCa were included in this review.

Evidence synthesis

Studies of immediate versus deferred ADT without local treatment consistently showed only limited benefit for overall survival (OS; hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.83–0.97) and cancer-specific survival (CSS; HR: 0.79; 95% CI, 0.71–0.89). In contrast, ADT as an adjuvant to radiation therapy in patients with high-risk localised disease or locally advanced disease was associated with substantial OS and CSS benefits. A similar benefit was seen in patients with proven systemic disease (node-positive patients after radical prostatectomy). Overall, the data suggest a clinically important survival benefit (HR for OS: 0.69; 95% CI, 0.61–0.79) when a local treatment has been applied to the primary tumour. Possible mechanisms of this therapeutic effect are discussed.

Conclusions

We conclude that an interaction between local treatment and ADT is suggested by this systematic review. In patients with advanced and aggressive disease who are at a high risk to die from PCa and who are treated for their primary tumour with curative intent, immediate and sustained ADT improves OS and CSS significantly. The local therapy in T3 and/or lymph node–positive disease is an essential part of the optimal treatment. However, this intensive treatment is unnecessary in a substantial number of patients with T3 and/or N1 disease with a slow natural history or high competing death risk.     

Does the Addition of Biologic Agents to Chemotherapy in Patients with Unresectable Colorectal Cancer Metastases Result in a Higher Proportion of Patients Undergoing Resection? A Systematic Review and Meta-analysis

Background

Surgical resection provides the best opportunity for cure for metastatic colorectal cancer. Whether addition of a biologic agent to chemotherapy improves the rate of conversion from unresectable to resectable disease remains uncertain. We carried out a systematic review of the literature and meta-analysis to define the impact of biologic agents on resection.

Methods

We searched Medline, Embase, CENTRAL, and PubMed for randomized controlled trials published up until April 2017 comparing chemotherapy and biologics (intervention) vs. chemotherapy alone (control) in treatment-naïve patients with unresectable metastatic colorectal cancer. Study selection, data abstraction, risk of bias, and quality of evidence assessment were performed in duplicate. Random-effects meta-analysis was used to estimate the pooled odds ratio (OR) for resection rate and corresponding confidence interval (CI).

Results

Nine studies, including a total of 4345 patients, were analyzed. Seven studies assessed epithelial growth factor receptor (EGFR)-directed monoclonal antibodies, and two used antiangiogenic agents. The addition of a biologic agent to chemotherapy was associated with higher resection rate (OR 1.47, 95% CI 1.07–2.02; resection rate 8.4 vs. 6.1%). Subgroup analysis based on mechanism of action of drugs showed benefit for resection rate only with EGFR-directed agents (OR 1.70, 95% CI 1.10–2.64). Heterogeneity among studies was low (I ²  =?34%).

Conclusions

The addition of biologic agents to systemic chemotherapy in patients with initially unresectable metastatic colorectal cancer improved resection rate. The optimal biologic agent for this outcome cannot yet be determined.