bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of time to definitive treatment for intermediate-risk and high-risk prostate cancer: Are delays associated with worse outcomes?
Authors: Nguyen David-Dan , Haeuser Lorine , Paciotti Marco , Reitblat Chanan , Cellini Jacqueline , Lipsitz Stuart R. , Cone Eugene Blanchard , Trinh Quoc-Dien 
Published: March 2021

233 Background: Prostate cancer (PCa) is an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized PCa are acceptable, especially for low-risk PCa. We sought to determine if treatment delays for intermediate-risk and high-risk PCa negatively impacted oncological outcomes. Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE, and the Cochrane Database of Systematic Reviews, from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence (BCR), pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer-specific survival, and overall survival. Due to significant heterogeneity between studies, a meta-analysis was not possible. Results: After identifying 1793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all PCa and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of BCR and pathological findings, but not worse survival. Conclusions: Definitive treatment for intermediate-risk and high-risk PCa can be delayed up to 3 months without any oncological consequences. Some evidence suggests that delays beyond 6-9 months are associated with a higher risk of BCR and varying worse pathological findings; as such, care should be given to provide definitive treatment within 9 months. To date, there is no evidence of worse cancer-specific or overall survival as a result of delayed treatment for intermediate-risk and high-risk PCa.
Post-radical prostatectomy (RP) outcome for patients with high-risk prostate cancer treated with intense neoadjuvant hormone therapy (NHT): Results of a pooled analysis of contemporary clinical trials.
Authors: McKay Rana R. , Berchuck Jacob E , Kwak Lucia , Xie Wanling , Silver Rebecca , Bubley Glenn , Chang Peter K. , Wagner Andrew , Zhang Zhenwei , Kibel Adam S. , Taplin Mary-Ellen 
Published: March 2021

238 Background: Patients with high-risk prostate cancer have an increased risk of recurrence and death from prostate cancer. Intense NHT prior to RP has been associated with favorable pathologic responses in a subset of patients with high-risk disease. We conducted a pooled analysis of post-RP outcomes of four, multicenter, randomized, clinical trials of intense NHT prior to RP. Methods: All patients included were enrolled on trials evaluating intense NHT followed by RP. The primary endpoint was time to biochemical recurrence (BCR), defined as the time from RP to prostate specific antigen (PSA) >0.1 ng/mL or start of first post-RP therapy. Secondary endpoints included metastasis-free survival (MFS), overall survival (OS), and time to testosterone recovery. We evaluated outcomes in the overall population, favorable responders (defined as a pathologic complete response or minimum residual disease ≤ 5 mm at RP), and non-responders. We correlated pathologic parameters, including RP pathologic response, PTEN status, ERG status, and presence of intraductal carcinoma with BCR. Results: 121 patients were included of whom 78.5% (n=95) had high-risk disease by NCCN risk categories. Following NHT, 20.7% (n=25) had 0-5 mm of residual tumor (including 9.1%, n=11, with pathologic complete response). Overall, 52 patients (43.0%) experienced BCR, of whom two were exceptional responders (Table). Testosterone recovery was observed in 94.0% of patients (n=109/116). PTEN loss and presence of intraductal carcinoma were associated with shorter time to BCR. Conclusions: In this pooled analysis of clinical trials, we demonstrate that patients who achieve a favorable pathologic response to NHT prior to RP experienced a decreased PSA relapse rate and prolonged time to BCR. Larger residual tumor volumes and tissue-based parameters, including PTEN loss and intraductal carcinoma, were associated with BCR. Additional follow-up is warranted to evaluate the impact on long-term outcomes. Clinical trial information: NCT00298155; NCT00924469; NCT01547299; NCT02268175 . [Table: see text]
Sixty-day unplanned readmissions after robot-assisted versus open-radical prostatectomy.
Authors: Lingamaneni Prasanth , Baral Binav , Moturi Krishna Rekha , Shrivastava Trilok , Darweesh Omnia , Gupta Shweta 
Published: March 2021

244 Background: Options for clinically localized prostate cancer include radical prostatectomy, radiation therapy and active surveillance. Robot-assisted radical prostatectomy (RARP) is increasingly being used, and now accounts for the majority of radical prostatectomies performed in the United States. The aim of our study was to evaluate differences in the patient population undergoing open versus robot-assisted prostatectomy, and to compare 60-day readmissions after index hospitalization for radical prostatectomy. Methods: We utilized the Nationwide Readmission database (NRD) to obtain data on patients with prostate cancer admitted in 2016 and 2017 for radical prostatectomy in the United States. We used T-test to compare means of continuous variables and chi-square test to compare proportions of categorical variables. Multivariable logistic regression was used evaluate risk factors for 60-day unplanned readmissions. Results: A total of 115,551 patients met the inclusion criteria, of which 80.1% underwent RARP. Patients undergoing RARP were slightly older (64.8 vs 63.1 years, p < 0.0001), more likely to have private insurance (51.7% vs 44.3%, p < 0.0001) and undergo surgery at a teaching hospital (83% vs 74.6%, p < 0.0001). Importantly, open prostatectomy (OP) patients had higher rates of co-morbidities, including, hypertension, diabetes mellitus, chronic kidney disease, obstructive lung disease, heart failure, coronary artery disease and malnutrition (p < 0.01 for these co-morbidities). Hospital stay was longer in those who underwent OP (3.1 vs 1.7 days, p < 0.0001), and they were more likely to be discharged to nursing facility (3.0% vs 0.4%, p < 0.0001) or with home health care (10.9% vs 4.8%, p < 0.0001). Hospitalization charges were higher in the RARP population ($60k vs 57k, p = 0.04). Inpatient mortality was low in both groups (0.3% for OP and ~0% for RARP, p < 0.001). 60-day readmission rate was higher in those who underwent OP (9.3% vs 5.0%, p > 0.0001). Overall, the three leading causes for readmission included sepsis (10.6%), post-procedure infection (8.4%) and venous thromboembolism (VTE, 8.3%). Even after adjustment for age and comorbidities, those who underwent OP had higher risk of all-cause readmission (aOR 1.39, 95% CI 1.25-1.53, p < 0.001) and readmissions for sepsis (aOR 1.36, 95% CI 1.02-1.81, p = 0.03) and post-procedure infection (aOR 1.38, 95% CI 1.06-1.81, p = 0.02). Risk of readmission for VTE was similar in both groups. Conclusions: Nationwide, there are differences in demographics and comorbid illness burden in prostate cancer patients selected for open and robot-assisted radical prostatectomy. Better short-term outcomes in the RARP cohort may be partially attributed to lower comorbidity burden in this group. However, despite adjustment for comorbidities, higher risk for all-cause readmissions and readmissions for infectious complications persisted in the OP group.
Extraperitoneal versus transperitoneal approach for robot-assisted radical prostatectomy: An updated systematic review and meta-analysis.
Authors: Uy Michael , Cassim Raees , Kim Jaehoon , Hoogenes Jennifer , Shayegan Bobby , Matsumoto Edward 
Published: March 2021

261 Background: Extraperitoneal RARP (EP-RARP) has recently become a popular surgical approach and is often compared to the transperitoneal RARP (TP-RARP). We conducted a systematic review and meta-analysis of the available literature to evaluate the differences in peri-operative characteristics, oncological and functional control, and surgical complications between EP-RARP and TP-RARP. Methods: A comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Google Scholar, and select conference abstract publications was performed for eligible studies comparing outcomes between EP-RARP versus TP-RARP. This was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered with PROSPERO. A leave-one-out sensitivity analyses was performed to control for heterogeneity and risk of bias. Results: A total of 16 studies (three randomized controlled trials, five prospective, and eight retrospective studies) were included with a total pooled population of 3897 patients including 2201 (56.5%) EP-RARPs and 1696 (43.5%) TP-RARPs. When compared to TP-RARP, EP-RARP offers faster operative time (MD: -14.4 minutes; 95% CI: -26.3, -2.3; p = 0.02), decreased length of post-operative stay (MD: -0.9 days, 95% CI: -1.3, -0.4, p < 0.0001), decreased rates of post-operative ileus (RR: 0.2, 95% CI: 0.1, 0.7, p = 0.009) and inguinal hernia formation (RR: 0.2, 95% CI: 0.1, 0.5, p = 0.001). There were no significant differences in total complications, estimated blood loss, positive surgical margins, or urinary continence at 6 months post-RARP. Conclusions: Based on the available evidence, EP-RARP delivered similar oncological and functional outcomes, while also offering faster operative time, decreased length of post-operative stay, and decreased rates of post-operative ileus and inguinal hernia formation when compared to the TP-RARP. These findings provide evidence-based data for surgical approach optimization and prompts future research to examine whether these findings hold true with recent advances in single-port RARP and outpatient RARP.
Evaluation of treatment patterns and outcomes in patients diagnosed with genitourinary (GU) cancers with linked claims plus prior authorization data.
Authors: Lal Lincy S. , Elliott Caitlin , Korrer Stephanie , DaCosta Byfield Stacey , Chastek Benjamin , Patel Tejas 
Published: March 2021

284 Background: Integration of clinical and claims data allows for the examination of outcomes and characteristics which is essential for real world evidence generation and clinical decision making. We describe utilization of clinical data collected from an oncology Prior Authorization (PA) program integrated with claims data to evaluate treatment patterns, resource utilization, and total costs of care during therapy for patients with newly diagnosed metastatic and non-metastatic renal (R), bladder (B), and testicular (T) cancers. Methods: Commercially insured patients with a GU cancer diagnosis, from 2/2016 to 12/2019 with both clinical information from a PA tool (based on NCCN guidelines) and claims from the Optum Research Database were identified. Demographics, clinical information (metastatic status and line of therapy), treatment duration, resource utilization, and all-cause costs were collected, and uploaded to a dynamic web-based Tableau dashboard. Analysis was conducted for non-metastatic and metastatic settings based on the first observed treatment episode. Drug additions or switches incremented line of therapy; single drug discontinuations did not. All cost data were adjusted to 2019 values. Results: A total of 3,736 patients were included; 13% were censored (i.e. on treatment at the end of the study period). 916 patients (25%) were metastatic and 2,820 (75%) were in their adjuvant/neoadjuvant (A/N) line. 60% of the population was ≥55 years old and 85% were male. The top regimen in A/N line for each cancer type were: nivolumab (R), BCG(B), bleomycin + carboplatin/cisplatin+ etoposide (T). The top regimen in metastatic cancer were: nivolumab (R), carboplatin/cisplatin + gemcitabine (B), bleomycin + carboplatin/cisplatin + etoposide (T). The median duration of A/N line ranged from 50(B) to 119(R) days while the median duration for metastatic line range from 71(T) to 82(R) days. The highest rate of inpatient admissions was observed in patients with R (31%). Of the three cancers, R was the most expensive in the A/N and metastatic settings with mean (standard deviation) costs of $192,308 ($269,358) and $136,293 ($146,632), respectively. Conclusions: Combination of clinical and claims data provide valuable information on real world outcomes in routine clinical care and may support treatment selection decisions at the point of care.
The impact of hypertension on response rates in patients with renal cell carcinoma.
Authors: Maslov Diana , Tawagi Karine , KC Madhav , Goel Richa , Yuan Helen , Bamnolker Adi , Blake Zoe , Song William , Johnson Daniel , Matrana Marc Ryan 
Published: March 2021

287 Background: There are many clinical trials that demonstrate the benefits of immunotherapies and targeted therapies in patients (pts) with advanced or metastatic RCC (mRCC). Most of these studies specifically exclude many real-world pts with comorbidities such as autoimmune disease, heart failure, and hypertension. Data on treatment efficacy and adverse events in patients with a history of uncontrolled hypertension is lacking, as there have been few studies analyzing more recently approved RCC drug regimens in real-world practice. Methods: We retrospectively collected data from pts with mRCC treated with immunotherapy and/or targeted therapies. Patient characteristics, performance status, treatment type, reason for treatment discontinuation, treatment response/progression per RECIST v1.1, survival, and presence of clinical trial exclusion criteria such as hypertension, heart failure, presence of autoimmune disease, renal or liver failure, and International Metastatic RCC Database Consortium (IMDC) Risk score were collected. Results: A total of 198 pts were included. The majority of patients received Tyrosine Kinase Inhibitors (TKIs) (42.42% pazopanib (n = 84), 21.71% sunitinib (n = 43), 13.64% cabozantinib (n = 27)), whereas 10.61% were on combination of axitinib + pembrolizumab (n = 21) and 11.62% received ipilimumab + nivolumab (n = 23), and. 71.72% of patients who qualified for systemic therapy had a history of uncontrolled hypertension, whereas 28.28 % of total patients had no history of uncontrolled hypertension. The median time on first-line treatment was 5.17 months. A history of hypertension did not significantly affect Overall Survival (OS), 15.90 months median OS for those with hypertension vs 27.80 median OS for those with no hypertension (p = 0.38). Median OS for all patients was 22.80 months. There was also no difference in response rate between those with a history of hypertension vs those with no history of uncontrolled hypertension (p = 0.65) or in Progression Free Survival (PFS) (p = 0.97) Data on how many patients developed exacerbations of hypertension on therapy will be available at time of presentation. Conclusions: Uncontrolled hypertension typically excludes patients from clinical trial enrollment. We found no difference in median OS in those with a history of hypertension compared to those with normal blood pressures. Further large-scale studies are needed to further determine outcomes in patients with hypertension on systemic therapy for mRCC.
Association of cabozantinib residual concentration (Ctrough) and blood clearance (Cl/F) with toxicity (tox) and progressive disease (PD) in metastatic renal cell carcinoma (mRCC) patients (pts): Results from a monocentric pharmacokinetics (PK) study.
Authors: Cerbone Luigi , Combarel David , Foulon Stéphanie , Geraud Arthur , Alves Carolina , Colomba Emeline , Carril Lucia , Derosa Lisa , Flippot Ronan , Mir Olivier , Escudier Bernard , Paci Angelo , Albiges Laurence 
Published: March 2021

292 Background: Cabozantinib is a TKI with a substantial efficacy in mRCC. It is associated with a relevant tox leading frequent dose modifications (DM) or drug discontinuations (DD). While an exposure/safety relation has been demonstrated for this drug, an exposure/efficacy relation is still unknown. Cl/F is a measure of elimination of a drug from blood or plasma and lower Cl/F of cabozantinib has been previously associated with increased DM rate in mRCC. Methods: We performed a monocentric PK (INDS MR 5612140520) study in patients with mRCC. Blood draw for assessment of cabozantinib PK was performed at least 8 hours from the last drug dose. Ctrough was estimated with the following equation: Ctrough=Cmeas*0,5DI-24/t1/2. Ctrough and Cl/F were compared in patients with or without a relevant tox and in PD pts vs SD/PR pts. Relevant tox was defined either as G3-4 tox or G2 tox leading to DM or DD. Differences in Ctrough and CL were assessed between the groups with Mann Withney U test. Results: From 01.10.19 to 31.08.20 66 pts were included in this analysis. Twenty one relevant tox and 29 PD were observed. Ctrough was higher in pts experiencing relevant tox than in those who did not: 624,6 ng/ml (IQR 494-1030,2 ng/ml) vs 505,2 ng/ml (IQR 329,2-910,2), p0.012. Conversely Cl/F was lower in relevant tox vs not tox1,85 l/h (IQR 1,4-2,2 l/h) vs 2.27 l/h (IQR 1,7-3,2), p 0.024. In PD pts, Ctrough was lower than in SD/PR pts: 419ng/ml (IQR 317,2 -549,1 ng/ml) vs 554 ng/ml (IQR 416,9-795,6), p 0.0105, while Cl/F was higher in PD patients: 2,6 l/h (IQR 2,14-3,44 l/h) vs SD/PR patients 1.9 l/h (1,930 l/h;IQR 1,35-2,53 l/h); p= 0.011. Time from day cycle 1 to PK blood draw was significatively longer in non-tox pts and numerically longer in PD pts, which have the lowest Ctrough and the highest Cl/F. Conclusions: Cabozantinib toxicity is associated to a higher Ctrough and a lower Cl/F. Cabozantinib PD is associated to a lower Ctrough and a higher Cl/F. Cl/F should be assessed alongside with Ctrough in Cabozantinib PK blood test; Ctrough may decrease and conversely Cl/F may increase with time on treatment. [Table: see text]
Osteonecrosis of the jaw in metastatic renal cell carcinoma (mRCC) patients treated with zolendronic acid and denosumab: An observational retrospective multicenter trial.
Authors: Stellato Marco , Santini Daniele , Sepe Pierangela , Anesi Cecilia , Claps Melanie , Mennitto Alessia , Guadalupi Valentina , Zecca Ernesto , Bracchi Paola , Procopio Giuseppe , Verzoni Elena 
Published: March 2021

299 Background: Bone is one of the most common site of metastasis occurring in 30% of metastatic renal cell carcinoma (mRCC) patients (pts)3,4. Skeletal metastases from mRCC are usually osteolytic and associated to high rate of morbidity and complication through skeletal related events (SRE). Bone-targeted therapies (BTT) such as zolendronic acid (ZOL AC) and denosumab (Dmab), shown to decrease the time-to-first and subsequent SREs12. Osteonecrosis of the jaw (ONJ) is a rare but potentially serious adverse event associated with BTT. It occurs in 1-2% of pts treated with BTT and in 10-17% of mRCC pts treated with ZOL AC or Dmab. Vascular endothelial growth factor-Tyrosine kinase inhibitors (VEGF-TKI) represent the backbone treatment for mRCC. Nevertheless, it is unclear whether the association of DMAB and ZOL AC to VEGF-TKITTagents could be associated to higher incidence of ONJ. Methods: We retrospectively collected data, from 2 Italian referring centers for mRCC, about 74 pts with bone metastases from mRCC who received, concurrently or sequentially to VEGF-TKI or immune-oncology (IO), AC ZOL and DMAB from January 2013 to January 2020. All pts provided informed consent for inclusion in the study. Results: All pts received VEGF-TKI as first line treatment. 17 pts received AC ZOL whereas 57 received DMAB. All pts received odontological consultation and orthopantomography before start BTT. The median time of Dmab and AC ZOL exposure was 11.6 months. ONJ occurred in 10/74 pts (7.4%): 6/10 pts were on first line treatment and 4/10 on second line. Treatments administered at the time of ONJ diagnosis were nivolumab (1/10), cabozantinib (2/10), sorafenib (1/10), sorafenib (1/10), sunitinib (4/10) and one pts was off therapy. Conclusions: In this real-life Italian population, treatment with BTT in mRCC pts treated with VEGF-TKI inhibitors and IO is associated to higher incidence of ONJ compared to previous report of pts treated with BTT for bone metastasis and lower compared to previous reports in mRCC. Despite the retrospective collection, we provided one of the largest sample of pts treated concurrently with VEGF-TKI or IO and BTT. Physicians should be careful in the use of BTT combined with other treatments in mRCC pts.
Long-term survival outcomes of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: A systematic review and individual patient data meta-analysis.
Authors: Esagian Stepan M. , Ziogas Ioannis A. , Kosmidis Dimitrios , Hossain Mohammad D. , Tannir Nizar M. , Msaouel Pavlos 
Published: March 2021

317 Background: The role of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy agents remains controversial. We used reconstructed individual patient data (IPD) to compare the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone for mRCC. Methods: We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: July 21, 2020). We reconstructed the Kaplan-Meier curves and subsequently recuperated IPD for overall (OS), progression-free (PFS) and cancer-specific survival (CSS) from individual studies. We performed one-stage random-effects frequentist and Bayesian meta-analyses of OS, PFS, and CSS using parametric and non-parametric estimates. We also performed a subgroup analysis focusing on upfront CN and excluding patients with deferred CN. The risk of bias was assessed using the ROBINS-I and RoB2 tools. Results: Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. No studies were found to be at critical risk of bias. A total of 3,990 patients were included, with 2,234 in the CN group and 1,756 in the non-CN group. Our frequentist meta-analysis showed superior OS (HR = 0.58, 95% CI: 0.54-0.62, p<0.0001) and CSS (HR = 0.63, 95% CI: 0.53-0.75, p < 0.0001) in favor of CN. No clinically meaningful differences were observed in the PFS between the two groups (HR = 0.90, 95% CI: 0.80-1.02, p=0.09). The OS benefit was also observed in the upfront CN subgroup (HR = 0.70, 95% CI 0.63-0.78, p<0.001). Similar results were obtained with non-parametric frequentist and Bayesian approaches (Table). Conclusions: The combination of CN and targeted therapy for mRCC is associated with superior long-term survival outcomes compared with targeted therapy alone. Careful patient selection based on prognostic factors is required to achieve optimal outcomes. [Table: see text]