bluuebunny/crossref_metadata_2025 huggingface dataset:
Waning efficacy of COVID-19 vaccination at six months in patients (pts) with genitourinary malignancies.
Authors: Zengin Zeynep Busra , Meza Luis A , Malhotra Jasnoor , Salgia Sabrina , Ely Jennifer , Hsu Joann , Kelley Erin , Mead Heather , Dizman Nazli , Chehrazi-Raffle Alex , Govindarajan Ameish , Muddasani Ramya , Chawla Neal Shiv , Dorff Tanya B. , Lyou Yung , Karczewska Ewa , Trent Jeffrey M. , Salgia Ravi , Altin John , Pal Sumanta K.
Published: February 2022

185

Background: Short-term effectiveness of COVID-19 vaccination is widely demonstrated, but the emerging real-world data suggest that immunity may wane over-time (Levin et al. NEJM 2021). Herein we aimed to explore the long-term efficacy of the COVID-19 vaccination among pts with genitourinary cancer. Methods: In this study, pts with genitourinary malignancies (prostate, kidney, and bladder cancers) who had not received COVID-19 vaccination were included. Blood samples were collected prior to and after one dose of either an adenovirus- or mRNA-based COVID-19 vaccine at the 2- and 6-month timepoints. Additional blood samples from pts receiving systemic treatment were collected at 3 consecutive therapy cycles following vaccination. Antibody titers were assessed using the SCoV-2 Detect IgG ELISA assay and results were reported as immune status ratios (ISR). T-cell receptor (TCR) repertoire sequencing was performed using the MiXCR software (MiLabs) and custom strips were used to assess TCR abundance and homology clustering. Results: A total of 183 pts were enrolled, and 136 pts provided baseline blood samples. Among these, 59 (8:51 F:M) provided samples for both the 2- and 6-month timepoints by the 10/6/2021 data cut-off. In this subset of pts, median age was 66 (range 48-85) and 33 (55.9%), 25 (42.4%), and 1 (1.7%) pts had prostate, kidney, and bladder cancer, respectively. A majority of the pts (93.2%) were on systemic treatment with 23.7% on immune checkpoint inhibitors, 18.6% on targeted agents, and 1.7% on chemotherapy. The most commonly administered vaccines were BNT162b2 (61.0%) followed by mRNA-1273 (37.3%) and Ad26.COV2.S (1.7%). The mean (±standard deviation) ISR values at baseline and 2 months were 0.68±1.59 and 6.62±1.75, respectively. At the 6-month timepoint, mean ISR was 5.46±1.61; this was significantly lower than the 2-month antibody titers (p < 0.0001), and reflects a reduction of 17.6%. Further data on TCR sequencing will be presented at the meeting. Conclusions: To our knowledge, this is the first data assessing the long-term serologic outcomes of COVID-19 vaccination in pts with cancer. Our data suggest waning immunity over time in cancer pts. Strategies to prolong host immunity against SARS COV-2 (e.g., booster vaccination) are likely warranted.
Aspartyl (Asparaginyl) β-hydroxylase (AABH) as a serum biomarker for prostate cancer, to identify prostate cancer, regardless of PSA level.
Authors: Moshiri Mahmood , Moshiri Arsha , Pashaei Hamed , Moshiri Kiarash , Nazari Reza , Monhemi Hassan
Published: February 2022

226

Background: Prostate Cancer (PC) is the most common form of cancer in men in the United States. In their lifetime, approximately 1 out of every 6 American men will develop PC. The chances of developing PC increase dramatically after age 50 with more than 72% of cases occurring in individuals over 65 years of age. Methods: We have investigated the use of aspartyl (asparaginyl) β-hydroxylase (AABH) as a cancer biomarker. We have developed a sandwich ELISA for its detection. Here this assay was utilized to screen sera from patients with prostate cancer and PSA values in various ranges. Results: AABH levels were assessed in sera from 263 individuals with PC and 73 men over 50 years of age not known to have cancer. The levels of AABH in the two groups were > 3.00 ng/ml and < 3.00 ng/ml, respectively. The overall sensitivity and specificity of the test were 97.5% and 96%. AABH and PSA levels were also compared. The AABH values and sensitivities in individuals with PC and PSA values in the ranges < 2 ng/ml, 2-4 ng/ml and > 4 ng/ml were > 3.00 ng/ml, 99% (n = 115); > 3.00 ng/ml, 98% (n = 64) and > 3.00 ng/ml, 95% (n = 114). Conclusions: The present study of AABH indicates that cancer group can be clearly distinguished from normal healthy controls. Moreover, the study indicates that AABH might be used to identify disease in individuals with questionable PSA values. These results support to the establishment of routine screening of serum AABH as a means to detect those who need referral for prostate biopsy. The use of AABH testing may enhance current prostate cancer screening practices by both identifying individuals with low but suspicious PSA values who should be recommended for biopsy and reducing the number of false biopsies indicated by positive PSA tests. Serum AABH levels are significantly elevated in individuals with prostate cancer. Using a cutoff value of 3ng/ml, overall sensitivity of the assay for prostate cancer is 97%. The test has a specificity of 96% in healthy men over 50 years of age. AABH is elevated in prostate cancer tissue but NOT in normal prostate or in Benign Prostatic Hyperplasia (BPH). Serum AABH levels are NOT correlate with PSA levels.
Preoperative PI-RADS scores are associated with prostate cancer upstaging on surgical pathology.
Authors: Pockros Benjamin , Stensland Kristian D. , Parris Molly , Frankenberger Edward , Canes David , Moinzadeh Alireza
Published: February 2022

228

Background: Prostate Imaging Reporting and Data System (PI-RADS) scores can help identify clinically significant prostate cancer and improve patient selection for prostate biopsies. However, the role of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear. The purpose of this study was to evaluate the association of PI-RADS scores with prostate cancer upstaging. Upstaging on final pathology is a surrogate for biochemical recurrence, morbidity, and mortality. Methods: All patients from a single high-volume institution who underwent a prostate multiparametric MRI and radical prostatectomy between 2016-2020 were included in this retrospective analysis. Univariable and multivariable analyses were conducted to investigate potential associations with upstaging events, defined by pT3, pT4, or N1 on final pathology. A logistic regression model and receiver operative characteristic curves were constructed for the prediction of upstaging events based on PI-RADS score, prostate-specific antigen density (PSA-D), and biopsy Gleason grade groups. Results: 294 patients were included in final analysis. Upstaging events occurred in 137 (46.5%) of patients. On univariable analysis, patients who were upstaged on final pathology had significantly higher PI-RADS scores (OR 2.34 95% 1.64 - 3.40, p < 0.001) but similar PSA-D (OR 2.70 95% 0.94 – 8.43, p = 0.188) compared to patients who remained pT1 or pT2 on final pathology. On multivariable analysis, PI-RADS remained independently significantly associated with upstaging, suggesting it is an independent risk predictor for upstaging. Lymph node metastasis only occurred in patients with PI-RADS 4 or 5 lesions (n = 15). Our model using PSA-D, biopsy Gleason grade, and PI-RADS had a predictive AUC of 0.69 for upstaging events, an improvement from 0.59 using biopsy Gleason grade alone. Conclusions: PI-RADS scores are independent predictors for upstaging events and may play an important role in forecasting biochemical recurrence and lymph node metastasis. PI-RADS scores could improve shared decision making and help set expectations with patients. Modern nomograms should be updated to include PI-RADS to predict lymph node metastases and the likelihood of biochemical recurrence more accurately.[Table: see text]
Successful same-day discharge for robot-assisted radical prostatectomy: A systematic review and meta-analysis.
Authors: Uy Michael , Millan Braden , Jones Conor , Sands David , Matsumoto Edward , Bay Benjamin , Shayegan Bobby
Published: February 2022

238

Background: In the current era of enhanced recovery after surgery (ERAS), same day discharge (SDD) following robot-assisted radical prostatectomy (RARP) is emerging as the standard of care. In order to implement a safe and efficient SDD pathway, it is imperative to appropriately select candidates and have established discharge criteria. We conducted a systematic review and meta-analysis to summarize published pathways, as well as to evaluate the differences in peri-operative characteristics, complication/readmissions rates, and satisfaction/cost data, between in-patient (IP) RARP versus SDD-RARP. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered with PROSPERO (CRD42021258848). A comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Google Scholar, and conference abstract publications was performed comparing outcomes between IP-RARP and SDD-RARP. A leave-one-out sensitivity analyses was performed to control for heterogeneity and risk of bias. Results: A total of 14 studies (eight prospective and six retrospective cohort studies) were included with a pooled population of 3795 patients, including 2348 (61.9%) IP-RARPs and 1447 (38.1%) SDD-RARPs. SDD pathways varied, though many commonalities were present in patient selection (minimal comorbidities and lived close to the hospital [≤ 50-150 km]), peri-operative recommendations (judicious intra-operative intravenous fluids and short-acting narcotics), and post-operative management (immediate ambulation and diet, and non-narcotic analgesia). When compared to IP-RARP, SDD-RARP had no differences in ≥ Grade 3 Clavien–Dindo complications (RR: 0.4, 95% CI 0.2, 1.1, p = 0.07), 90-day readmission rates (RR: 0.6, 95% CI 0.3, 1.1, p = 0.10), or unscheduled ED visits (RR: 1.0, 95% CI 0.3, 3.1, p = 0.97). Cost savings per patient ranged between $367-2109 (USD), and overall satisfaction was high between 87.5-100%. Conclusions: Same day discharge following RARP is both feasible and safe, with comparable complication and readmission rates to IP-RARP. Additionally, SDD offers healthcare cost-savings with high patient satisfaction rates. Data from this study will further inform the uptake and development of future SDD pathways in contemporary urological care such that it may be offered to a broader patient population.
Salvage radiotherapy guided by functional imaging for macroscopic local recurrence following radical prostatectomy: A multicentric retrospective study.
Authors: Benziane-Ouaritini Nicolas , Zilli Thomas , Giraud Antoine , Ingrosso Gianluca , Di Staso Marco , Trippa Fabio , Meyer Emmanuel , Francolini Giulio , Schick Ulrike , Cosset Jean Marc , Martin Etienne , Ferrari Victoria , Achard Verane , Giraud Nicolas , Pasquier Corentin , Magné Nicolas , Pasquier David , Supiot Stephane , Latorzeff Igor , Sargos Paul
Published: February 2022

251

Background: For prostate cancer (Pca), salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) is currently the only curative treatment option in case of post-radical prostatectomy (RP) biochemical relapse (BR). Functional imaging techniques have shown that macroscopic recurrence (MR) in the prostate bed (PB) are frequent. In this study, we aimed to assess efficacy and safety of sRT in patients with MR inside the PB proven by functional imaging. Methods: A multicenter retrospective study was conducted in 16 European centers. Patients were included if they displayed BR after RP for Pca, with MR only in the PB proven by functional imaging. All patients had to be eligible for sRT. The overall population was divided along 4 groups according to the delivered treatment: dose escalation on MR (A), dose escalation on PB (B), double dose escalation MR+PB (C), no dose escalation (D). The primary endpoint was progression-free survival (PFS). Secondary outcomes included the metastasis-free survival (MFS), biochemical PFS (bPFS) and overall survival (OS). Grade ≥2 genito-urinary (GU) and gastro-intestinal (GI) acute and late toxicities were collected. Results: Between January 2000 and December 2019, 363 patients with isolated MR after RP for Pca were treated by sRT. The median pre-sRT PSA level was 0.63ng/mL (range, 0.2-23.6). At the time of BR, 266 (73%) patients presented MR in the PB proven by magnetic resonance imaging, and 110 (30%) by positron emission tomography. The median follow-up was 53.6 months (range, 47.52; 58.32). The 5-year PFS and MFS were 70% (95%CI [63.8-75.4]) and 83.7% (95%CI [78.4-87.8]), respectively. Grade ≥2 GU and GI late toxicities were found in 43 (12%) and 11 (3%) patients, respectively. A 5-year PFS benefit was highlighted for groups A, B and C (313 patients) when the MR dose was ≥72Gy: 72,8% (95%CI 64.6-79.4) versus 60.3% (95%CI 48,4-70,3), p = 0.03. Conclusions: In a modern series integrating functional imaging data, we confirmed that sRT is effective in the event of MR inside the PB, with an acceptable toxicity profile. Prospective data should further investigate the correlation between MR-targeted dose escalation and PFS.
High-dose external BEAM intensity-modulated radiotherapy (HD-IMRT) versus intensity-modulated radiotherapy plus HDR brachytherapy boost (LD-IMRT+HDR-B) dose escalation for intermediate- or high-risk prostate cancer
Authors: Guix Ines , Bartrina Jose Maria , Panichi Marco , Tello Jose Ignacio , Garcia Ivan , Del Campo Jose Maria , Quinzaños Luis , Lacorte Teresa Maria , Guix Teresa , Guix Benjamin , Guix Benjamin
Published: February 2022

263

Background: To report early & late toxicity & biochemical outcome in a prospective series of 1,465 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-IMRT or with LD-IMRT+HDR-B. Methods: Between 12/1999 and 10/2011, 1,465 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-IMRT to the prostate in 38 fractions (group 1; 733 patients) or 46 Gy LD-IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 732 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumor’s characteristics. Toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 94 pts of group 1 (12.8%) and 20 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 49 pts in group 1 (6.7%) and 10 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 112 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.001) in group 1 and 2 respectively; free-from-metastases survival 93.9% and 97.8% (p<0,002)for group 1 and 2 respectively; and cause-specific survival 90.1% and 98.2% (p<0.001). No complications grade 2-4 were seen in either group. Conclusions: IMRT + HDR brachytherapy boost was a safe and extremely effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced. Control rates were significantly better in the HDR-boosted patients as expected by higher effective-dose. Brachytherapy boost treated patients had a significant longer survival.
Survival outcomes in men with unfavorable intermediate-risk and high-risk prostate cancer treated with prostate-only versus whole pelvic radiation therapy.
Authors: Andruska Neal , Fischer-Valuck Benjamin Walker , Juarez Diaz Elizabeth , Agabalogun Temitope , Brenneman Randall , Gay Hiram Alberto , Michalski Jeff M. , Baumann Brian C.
Published: February 2022

264

Background: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT). Treatment is frequently intensified by electively treating the pelvic lymph nodes with whole pelvis radiotherapy (WPRT), but practice patterns differ and the benefits of WPRT are not clearly defined, with mixed results from clinical trials. The recent POP-RT trial showed improved biochemical control with WPRT but most patients were staged with PET/CT scan. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy in patients staged using conventional imaging. Methods: Men diagnosed between 2008-2015 with UIR or high-risk prostate cancer were retrospectively reviewed from the National Cancer Database (n = 28,724). Patients with involved nodes or distant metastases were excluded. Men received EBRT to a dose of 72-86.4 Gy and either prostate-only RT ± ADT (n = 13,549) or WPRT plus prostate RT ± ADT (n = 15,175). WPRT was delivered using a dose range of 40-50.4 Gy (1.8 – 2.0 Gy/fraction). The MSKCC nomogram was used to calculate risk of lymph node involvement. Unweighted or inverse probability of treatment weighting (IPTW) was used to perform multivariable analysis (MVA) using Cox regression modeling to compare OS hazard ratios, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, education, income, treatment facility type, PSA, Gleason score, clinical T-stage, use of ADT, lymph node risk score, and radiation dose. Results: 53% of men received WPRT, with national utilization of WPRT increasing from 2008 to 2015. For every 1% increase in risk of lymph node involvement, there was a 1% increased risk of death ( P<.001). WPRT trended toward improved OS in all men with UIR or high-risk (Hazard Ratio (HR): 0.95 [95% Confidence Interval: 0.90-1.006], P=.07). WPRT correlated with improved OS in men with grade group 5 (GG5) disease (HR: 0.87 [0.78-0.98]. P=.02) or risk of lymph node involvement ≥ 10% (HR: 0.93 [0.87-0.99], P=.03). Conclusions: WPRT is associated with improved OS in men with a lymph node risk score ≥ 10% or GG5 disease. These results complement the recent POP-RT randomized trial in mostly PET/CT-staged patients, demonstrating that a more heterogenous population of men staged without functional imaging appears to benefit from WPRT.
A genomic classifier for prostate cancer correlates with adverse pathologic features: Transcriptomic features of cribriform and intraductal carcinoma of the prostate.
Authors: Lone Zaeem M , Benidir Tarik , Rainey Magdalena , Nair Monica , Davicioni Elai , Gibb Ewan , Williamson Sean , Nguyen Jane , Gupta Shilpa , Ornstein Moshe Chaim , Tendulkar Rahul D. , Weight Christopher , Klein Eric A. , Mian Omar Y.
Published: February 2022

268

Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p<0.001). Patients who were CF+/IDC+ had a higher percentage of Gleason grade group >3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p<0.001). On multivariate logistic regression, predictors of high-risk GC score were presence of CF+/IDC+ features on final pathology (OR: 3.94, p<0.001) and pathologic Gleason grade group >3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p<0001). Conclusions: This is the largest series investigating the association of a clinically validated genomic classifier and pathologic features such as cribriform and intraductal carcinoma. These findings have implications for the use of genomic classifiers in settings where expert GU pathology is not readily available and in potentially unmasking adverse histology at the time of biopsy.[Table: see text]
Hereditary cancer risk assessment in the community urology practice setting.
Authors: Shore Neal D. , Lenz Lauren , Flake Darl D. , Meek Stephanie , Davis Thaylon , Copeland Karen , Finch Rob , Schiff William , Korman Howard , Rao Manoj , Belkoff Laurence , D'Anna Richard , Slavin Thomas , Cohen Todd
Published: February 2022

278

Background: Professional guidelines recommend hereditary cancer risk assessment (HCRA) for men with prostate cancer to inform both risk of cancer (primary or subsequent) and treatment decisions. The objectives of the study were to evaluate the feasibility of integrating a HCRA protocol in urology practice for patients with prostate cancer and determine the response of providers and patients to the HCRA protocol. Methods: This prospective study was divided into 4 segments: process integration (4 wks.), practice (4 wks.), post-integration (8 wks.), and follow up (10 wks.). Study site staff were trained to perform HCRA for men with prostate cancer (integration). The sites then incorporated recommendations from the integration process into their normal practice workflow (practice). During the post-integration period, the HCRA process was implemented with eligible patients consented to participate. Eligible patients were ≥18 years old, had a personal history of prostate cancer, and met National Comprehensive Cancer Network guidelines for genetic testing (2.2018). Patients and providers completed surveys regarding testing ≥ 8 weeks of test delivery or 1 week of end of data collection period, respectively (follow up). Results: In the 8 weeks prior to the study, 4.2% of patients completed testing at the study sites. During the study, 8.4% of patients completed testing, about 1/2 of eligible patients screened. Of all patients who completed testing and consented for their results to be summarized (N = 182), 10.4% (N = 19) tested positive for a single pathogenic variant (PV; monoallelic MUTYH N = 4; BRCA2 N = 3; ATM, BRCA1, BRIP1, CHEK2, HOXB13 N = 2 each; RAD51C, RAD51D N = 1 each). Not all men who tested positive or a PV reported a family history of cancer and not all PVs detected were in known prostate cancer risk genes. During follow up, most providers (61.0%) felt HCRA was as important as other assessments regularly performed and 68.3% planned to continue to use the HCRA process. In contrast, only 9.8% of providers did not believe HCRA was as important and 12.2% did not plan to continue to use the process. Of the patients that responded to the survey (N = 166), most had shared (62.0%) or planned to share (25.3%) their results with family members post-testing. Conclusions: Urologists and patients responded favorably to HCRA protocol integration. Based on this study, education around and incorporation of an HCRA process in a community urology practice setting for men with prostate cancer appears effective at increasing appropriate uptake of genetic testing. Clinical trial information: NCT04015102.
Disease progression and competing mortality for men undergoing active surveillance for low-risk prostate cancer.
Authors: Guram Kripa , Nelson Tyler J. , Deka Rishi , Sherer Michael Vincent , Rodrigues De Moraes Gustavo , Rose Brent S.
Published: February 2022

282

Background: Active surveillance is a common management strategy for men with low-risk prostate cancer. However, there is some concern that delaying definitive therapy could lead to progressive disease and a missed opportunity to cure the cancer. We sought to study the impact of Gleason grade progression on the risk of metastases and prostate cancer-specific mortality (PCSM). We then sought to compare the risks of PCSM with the risk of competing mortality in this real-world cohort of men on active surveillance. Methods: This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure of patients with a diagnosis of low-risk prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1, clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower. Active surveillance was defined as no definitive treatment within the first year after diagnosis with at least 1 additional re-staging biopsy after diagnostic biopsy. We identified men with pathologic upgrading to ≥GG2 and ≥GG3. We calculated the cumulative incidence of metastases, PCSM, and non-cancer mortality for men with and without pathologic upgrading. Results: The cohort included 8562 men with low-risk PC. Pathologic upgrading to ≥GG2 and ≥GG3 occurred in 3227 and 1200 men, respectively. For all patients, the 8-year cumulative incidence of metastases and PCSM was 0.8% (95% CI: 0.6-1.0%) and 0.4% (CI:0.3-0.6%), respectively. Pathologic upgrading to ≥GG2 was associated with an increased risk of metastases at 8 years (1.2% vs 0.5%, p < 0.001). Pathologic upgrading to ≥GG3 was also associated with an increased risk of metastases at 8 years (2.7% vs 0.5%, p < 0.001). In contrast, pathologic upgrading to ≥GG2 was not associated with an increased risk of PCSM at 8 years (0.5% vs 0.4%, p = 0.793). Similarly, pathologic upgrading to ≥GG3 was not associated with an increased risk of PCSM at 8 years (0.7% vs 0.4%, p = 0.82). The 8-year cumulative incidence of non-cancer mortality for all patients was 6.5% (95% CI:5.9-7.1%). Overall, the risk of non-cancer mortality was 16.25 (6.5/0.4) times higher than the risk of PCSM, regardless of upgrading status. Conclusions: For men with low-risk PC on active surveillance, pathologic upgrading was associated with a small increased risk of metastases but no increased risk of death from prostate cancer. Regardless of upgrading status, the risk of non-cancer mortality was substantially higher than the risk of PCSM. Future work is required to better tailor the intensity of follow up for surveillance protocols for men at risk of competing mortality.
Growth kinetics and progression rates of cystic renal masses on active surveillance.
Authors: Tse Justin , Shen Luyao , Yoon Luke , Kamaya Aya
Published: February 2022

298

Background: The Bosniak classification is used to risk stratify the probability of cancer among cystic renal masses using CT or MRI and assigns a class ranging from I-IV. Bosniak III and IV masses have the highest probabilities of cancer and are treated similarly to solid renal masses per 2021 American Urological Association (AUA) Guidelines. The purpose of this study was to determine the growth kinetics and progression rates of unresected Bosniak III and IV masses defined by Bosniak Classification, version 2019 (v2019). Methods: In this retrospective and IRB-approved study, CT and MRI images of 107 cystic renal masses from 100 patients (34 women, 66 men; range 28-92 years) with unresected Bosniak III and IV masses from 2005-2021 were reviewed. Cystic renal masses on baseline imaging were assigned a category based on v2019 by two abdominal radiologists, with discrepancies resolved by a third, such that each mass had a single Bosniak class assignment. Mass dimensions over serial imaging were measured using orthogonal planes by a radiologist with 3D laboratory training. Linear growth rate (mm/year) and volumetric growth rate (mL/year) were calculated. “Progression” off of active surveillance was defined as any of the following: linear growth rate > 5 mm a year, volume doubling rate ≤ 1 year, or increased stage based on TNM. Results: 107 cystic renal masses were categorized as 51 Bosniak III and 56 Bosniak IV masses on baseline exam. Median follow-up time was 406 days. Linear growth rate for Bosniak III masses was 0.4 ± 4.3 mm/year while linear growth rate for Bosniak IV masses was 2.3 ± 4.9 mm/year (p = 0.036; Student’s t-test). 12/51 (24%) Bosniak III masses progressed based on above definitions while 26/56 (46%) Bosniak IV masses progressed (p = 0.016; Fisher’s exact test). 13 masses upgraded from a Bosniak III to IV during surveillance, but category upgrades were not associated with progression (p = 0.131; Fisher’s exact test). 2 patients developed lung metastases; both masses were Bosniak IV and were biopsy proven papillary and clear cell renal cell carcinomas. Conclusions: Although currently treated similarly by AUA Guidelines, unresected Bosniak IV masses grow faster than Bosniak III masses and are more likely to progress off of active surveillance.
Association of cabozantinib dose reductions for toxicity with clinical effectiveness in metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer Information System (CKCis).
Authors: Graham Jeffrey , Basappa Naveen S. , Ghosh Sunita , Zhang Hanbo , Hansen Aaron Richard , Lalani Aly-Khan A. , Heng Daniel Yick Chin , Soulieres Denis , Castonguay Vincent , Kollmannsberger Christian K. , Pavic Michel , Wood Lori , Kapoor Anil , Bjarnason Georg A.
Published: February 2022

316

Background: Cabozantinib (cabo) is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in mRCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. We explored whether cabo dose reductions (a surrogate for toxicity) were associated with improved clinical outcomes in mRCC. Methods: Using the CKCis database, we performed an analysis of patients treated with cabo in the second-line or later between 2011-2021. We divided the cohort into those needing a dose reduction (DR, defined as less than the starting dose at time of treatment discontinuation) and those who did not (no-DR). We compared outcomes by dose reduction status, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS). Results: We identified 260 patients who received cabo, of which 103 (41.0%) needed a DR. Across all lines, the ORR was similar between the DR and non-DR groups: 19.6% vs. 18.9% (p = 0.903) respectively. The median TTF was 12.75 months (95% CI 10.38 – 17.64) in the DR group vs. 6.44 months (95% CI 5.49 – 8.67) in the no-DR group. After adjusting for IMDC risk, the hazard ratio (HR) for TTF comparing DR vs. no-DR was 0.69 (95% CI 0.50 - 0.97, p-value = 0.03). The median OS was 29.6 months (95% CI 19.58 – 42.64) in the DR group vs. 15.28 (95% CI 11.04 – 22.64) in the no-DR group. After adjusting for IMDC risk, the HR for OS comparing DR vs. no-DR was 0.65 (95% CI 0.43 - 0.98, p = 0.04). Conclusions: Cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, appear to be associated with improved TTF and OS in mRCC. Toxicity driven/individualized dosing strategies for cabo alone and in combination with immunotherapy, warrant further investigation.[Table: see text]
Efficacy of first-line combination therapy in metastatic renal cell carcinoma (mRCC) patients (pts) with poor performance status (PS).
Authors: Carril Lucia , Colomba Emeline , Romero-Ferreiro Carmen , Cerbone Luigi , Ratta Raffaele , Barthélémy Philippe , Vindry Clarisse , Cherifi Francois , Boughalem Elouen , Linassier Claude , Fornarini Giuseppe , Gross-Goupil Marine , Saldana Carolina , Martin Soberón Maria Cruz , de Velasco Guillermo , Pernaut Cristina , Alves Costa Silva Carolina , Flippot Ronan , Escudier Bernard , Albiges Laurence
Published: February 2022

320

Background: Immune checkpoint combination therapy (ICI-combo) is the new standard of care for mRCC in first-line setting. However, pts with poor PS (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-combo in this group of pts is still unknown. Methods: We performed a multicentre retrospective study of PS≥2 mRCC pts who received ICI-combo, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (PA) as first-line treatment between 2017-2021. Patient’s characteristics, clinical outcomes and toxicity were retrospectively reviewed. We analysed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and grade ≥3 treatment-related adverse events (G≥3 AEs) in pts treated with NI or PA. The association between LIPI (Lung Immune Prognostic Index) and ORR, PFS and OS was also evaluated. Results: We identified 56 mRCC pts with PS≥2 treated with ICI-combo across 13 institutions. Thirty-six and 20 pts were treated with NI and PA respectively. Median age at diagnosis was 64 (31-83) years, 38 (68%) were male, 16 (29%) had prior nephrectomy and 40 (71%) had synchronous metastatic disease at diagnosis. Respectively, 19 (34%) and 37 (66%) pts were intermediate and poor risk according to IMDC. Fifty pts (89%) were clear cell RCC, and only 4 pts had sarcomatoid features reported. At the time of analysis (median follow-up 11.1 months(mo)) 45% pts were dead. The ORR for the entire cohort was 27%; ORR was numerically higher with PA (42%) than with NI (20%) but did not reach statistical significancy (p=0.157). Median PFS (mPFS) and mOS in the entire cohort were 4.4 mo and 15.9 mo respectively. No significant differences in PFS, OS or the rate of G≥3AEs were seen between the NI and PA groups. Efficacy and toxicity outcomes are described in the table below. No significant differences in OS or PFS according to the IMDC risk score were observed (p=0.818). However, LIPI was significantly associated with OS (poor LIPI: HR=8.18; p=0.004) and PFS (Intermediate LIPI: HR=2.4; p=0.048 and poor LIPI: HR=8.59; p<0.001). LIPI was predictive of response in patients treated with NI (p=0.024). Conclusions: We report the first cohort of PS≥2 mRCC pts treated with ICI-combo in first-line setting. No significant differences in ORR, PFS or OS were seen between NI and PA. LIPI was significantly associated with both OS and PFS, and was predictive of ORR in the NI group. Prospective real-world studies are needed to confirm these results.[Table: see text]
Cost effectiveness of adjuvant pembrolizumab after nephrectomy for RCC: Insights for patient selection from a Markov model.
Authors: Sharma Vidit , Wymer Kevin M , Joyce Daniel D. , Moriarty James P. , Borah Bijan J , Thompson R. Houston , Costello Brian Addis , Leibovich Bradley C. , Boorjian Stephen A.
Published: February 2022

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Background: KEYNOTE-564 demonstrated that adjuvant pembrolizumab after nephrectomy for high-risk clear cell renal cell carcinoma (RCC) decreased the risk of disease progression and – albeit with immature follow-up (2 years) – found a signal of improved overall survival as well. Herein, we used extrapolations from a Markov-model, accounting for the costs and toxicities of pembrolizumab relative to its efficacy, to investigate its utility at a population level. Methods: A decision-analytic Markov Model was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus placebo after nephrectomy for high risk RCC, using data from KEYNOTE-564 to inform model probabilities. Transition probabilities not found in KEYNOTE-564, in addition to utility values, were extracted from the literature. Base case analyses were conducted with 5-year and 15-year time horizons (using extrapolations from 2-year outcomes), and 3-week time cycles. Primary outcomes were Quality-adjusted life years (QALYs), 2021 US Medicare costs, and Incremental cost-effectiveness ratios (ICERs). The willingness-to-pay threshold was set at $100,000/QALY. One-way sensitivity analyses were used to identify cost-effectiveness thresholds of individual parameters while probabilistic sensitivity analyses with 100,000 Monte-Carlo simulations were used to simultaneously vary all model inputs. Results: Pembrolizumab was associated with higher QALYs and costs relative to placebo (Table). Pembrolizumab was not cost-effective at a 5-year time horizon but was cost-effective at 15 years and beyond. One-way sensitivity analysis noted that pembrolizumab became cost-effective at 5-years if: 1) its administration cost was less than $5,064 (base = $10,278) or 2) if the 5-year risk of progression was 18.8% higher in placebo vs pembrolizumab (base = 9%). Using pembrolizumab’s reported hazard ratio of 0.68 for progression from KEYNOTE-564, we estimated that pembrolizumab would be cost-effective at 5-years for all patients with a Mayo Progression Free Survival Score of 10 or higher. Probabilistic sensitivity analysis found that pembrolizumab was cost-effective for 29% and 58% of microsimulations at 5 and 15 years, respectively. Conclusions: At current prices, adjuvant pembrolizumab was not cost-effective for all trial patients at a population level at 5-years after treatment but may be cost-effective for time horizons over 15 years. Instead, adjuvant pembrolizumab was found to be cost-effective only for the highest risk subsets of RCC at 5-years. Longer term trial data of progression-free survival and overall survival are necessary to confirm these extrapolations.[Table: see text]
Does presence of diabetes mellitus impact patient oncological outcomes in renal cell carcinoma: A multicenter analysis.
Authors: Saidian Ava , Walia Arman , Patil Dattatraya , Saito Kazutaka , Patel Devin , Nguyen Mimi Vu , Chakoumakos Madison , Ghali Fady , Narasimhan Rekha S , Perry John M , Meagher Margaret , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj A.
Published: February 2022

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Background: Diabetes mellitus (DM) has been hypothesized to be a risk factor for development of renal cell carcinoma (RCC). We evaluated impact of DM on survival outcomes in RCC. Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC). The cohort was divided into three subgroups (patients with stage I vs. stage II vs. stage III RCC) for descriptive, survival and multivariable analysis of outcomes. Kaplan Meier Analysis (KMA) was used to compare diabetic and non-diabetic patients in the different stage subgroups to evaluate overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Cox Regression multivariable analysis (MVA) was used to elucidate independent risk factors for all-cause mortality (ACM). Results: 2,927 patients with stage I RCC (709-DM/ 2218 non-DM), 2,513 with stage II RCC (688 DM/1825 non-DM) and 460 with stage 3 RCC (355 DM/ 105 non-DM) were analyzed. MVA revealed DMII having no impact on CSM (p=0.118) or PFS (p=0.316) across all stages. MVA for ACM revealed age (HR 1.026, p<0.001), male sex (HR=1.425, p<0.001), hypertension (HR=1.693, p <0.001) and tumor size (HR=1.064, p<0.001) as independent risk factors. KMA identified increased ACM in stage I (p<0.001) and stage III (p<0.001) RCC patients with non-DM compared to diabetic patients. Conclusions: Our findings suggest that DM may have impact on survival of in RCC, but this impact is mostly driven by non-oncologic, as opposed to oncologic effects. Further investigation is requisite.
The survival outcomes of the metastatic renal cell carcinoma with rhabdoid differentiation in immunotherapy era: Princess Margaret Cancer Center experience.
Authors: Al-Ezzi Esmail Mutahar , Mittal Abhenil , Wilson Brooke , Iafolla Marco , Spiliopoulou Pavlina , Sridhar Srikala S. , Fallah-Rad Nazanin , Chung Peter W. M. , Perlis Nathan , Hansen Aaron Richard
Published: February 2022

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Background: Patients (pts) diagnosed with metastatic renal cell carcinoma (mRCC) with rhabdoid differentiation (RD) have a poor prognosis due to aggressive tumor behavior and inherent treatment resistance to targeted therapies. However, recent data has demonstrated the survival benefit of immunotherapy (IO) in mRCC. Here, we report survival outcomes of pts with mRCC with RD treated with targeted therapy and or IO. Methods: This retrospective survival analysis was performed in pts with mRCC and RD treated with targeted treatment and IO at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Overall survival (OS) was calculated using the Kaplan-Meier method (log-rank). OS hazard ratio (HR) were calculated using cox proportional hazards model. IBM SPSS Statistics v26 was used to conduct statistical analyses. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. A total of 57 (12%) pts diagnosed with mRCC had RD and were treated with targeted and or IO agents. Of these, 42 (73.7%) pts had pure RD and 15 (26.3%) pts had mixed RD and sarcomatoid features. Median age was 62 yrs (35-86yrs) and 42 (73.7%) were male. Overall, as per the IMDC score, 5(8.8%), 27(47.4%) and 25(43.8%) pts were categorized as good, intermediate, and poor risk, respectively. In total, 34 (59.6%) pts were treated with targeted therapy only during their first and second line treatment course and 23 (40.4%) pts received IO alone or in combination with targeted treatment in the first or second line. With a median follow up of 53.4 months (range, 38.3-68.4 months), the median OS for the whole mRCC with RD cohort was 23.1 months (95% CI: 14.6-31.5). The median OS in all pts treated with targeted therapy only vs IO receipt was 13.1 months (95%CI: 5.4-20.8 months) vs not reached; p = 0.026, respectively. HR for OS was 0.44 (95%CI: 0.22-0.93; p = 0.03) favoring IO receipt. Conclusions: While the number of pts included in our retrospective review was small, our analysis has suggested that pts with mRCC and RD have poor survival outcomes that may be improved with IO treatment. RD is a histopathological feature that could identify pts who may benefit from IO therapy. Further analysis is needed to explore the impact of RD on IO treatment response.
Network meta-analysis (NMA) of second-line (2L) treatment options in metastatic renal cell carcinoma.
Authors: Recio-Boiles Alejandro , Obeng-Kusi Mavis , Choi Briana , Abraham Ivo
Published: February 2022

337

Background: Immune checkpoint inhibitors, in combination either with a cytotoxic T-lymphocyte-associated protein 4 or tyrosine kinase inhibitor are approved for first-line (1L) therapy of metastatic renal cell carcinoma (mRCC). Of those, several have been shown to improve median progression-free survival (mPFS) in the 2L. A recent NMA by Irbaz et al. (PMID 33824031) identified the most effective 1L treatments for mRCC. In the absence of head-to-head randomized clinical trials (RCT), we performed an indirect comparison of 2L treatments for mRCC. Methods: We conducted literature searches in Medline, Embase, Cochrane Library, and Google Scholar to identify RCTs evaluating 2L treatments in mRCC. We extracted the mPFS hazard ratios (HR) and 95% confidence intervals (CI). We used a normal likelihood model that incorporates log HRs of the treatment differences for conducting the NMA. P-scores, measuring the certainty that one treatment is better than another averaged over all competing treatments, were used to rank treatments. Higher p scores indicate better outcomes. Data were analyzed with R netmeta package v.1.5-0. Results: All 8 therapies included in this analysis showed benefits in mPFS over placebo (Table). The combination of lenvatinib+everolimus had the lowest hazard of disease progression or death and pazopanib was the highest compared to placebo. Lenvatinib+everolimus ranked highest with a p-score of 0.96 followed by cabozantinib (0.88), and lenvatinib (0.79); with others having p-scores of 0.60 or less (placebo p-score 0.00). Conclusions: This NMA revealed that lenvatinib+everolimus and cabozantinib are most likely to produce the highest PFS benefit in 2L in mRCC. Future studies are needed to evaluate 1L and 2L sequencing options to further inform clinical practice. [Table: see text]
Efficacy and safety of nivolumab in renal cell carcinoma patients with BONE metastases: Results of the GETUG: AFU 26 nivoren multicenter phase II study.
Authors: Velev Maud , Dalban Cécile , Chevreau Christine , Gravis Gwenaelle , Negrier Sylvie , Laguerre Brigitte , Gross-Goupil Marine , Ladoire Sylvain , Ferrari Victoria , Geoffrois Lionnel , Curcio Hubert , Priou Frank , Thomas Quentin Dominique , Mione Cécile , Barthélémy Philippe , Tantot Florence , Escudier Bernard , Chabaud Sylvie , Albiges Laurence , Thibault Constance
Published: February 2022

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Background: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies in which patients were treated with antiangiogenic agents. Since the development of immune checkpoint inhibitors, few data are available regarding the prognosis impact of BM or the efficacy and safety of checkpoint inhibitors in patients with bones metastatic RCC. GETUG-AFU26-NIVOREN (NIVOREN) is a French multicenter prospective study in which patients were treated with nivolumab after failure of one or more antiangiogenic tyrosine kinase inhibitors. We therefore aim to evaluate the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients with BM enrolled in NIVOREN trial. Methods: All adult patients with BM at inclusion were included in our study. The primary endpoint of this ancillary study was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE) in patients with BM. Clinical data were collected prospectively, except for SRE data which were collected retrospectively in a complementary consent report form. Results: Among 720 patients treated with nivolumab in the NIVOREN study, 194 had BM at inclusion. After a median follow-up of 23.9 months, the median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (HR = 1.42 CI95% [1.13-1.79], p = 0.0023). After adjustment on sex, age, IMDC group and line of treatments, the difference was not significant (HR = 1.24, CI95% [0.98-1.56], p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, HR = 1.30 CI95% [1.08-1.56]), as well as the ORR (14.8% versus 23.3%). The safety profile was similar between patients with or without BM at inclusion. The incidence of SRE in the BM population was 36% during the treatment period with nivolumab. A post-hoc analysis evaluating the impact of bone-targeting agents in association with nivolumab on SRE incidence was performed. There was a statistically significant benefit in patients treated with bone-targeting agents on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895], p = 0.0276). Conclusions: Nivolumab is associated with shorter OS, PFS, and lower ORR in patients with BM. Our study confirms, in the era of immunotherapy that patients with BM are associated with poorer prognosis and suggests that association with bone-targeting agents decreases the incidence of SRE. Clinical trial information: 2015-004117-24.