bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of abiraterone acetate for high-risk nnon-metastatic prostate cancer.
Authors: Lester-Coll Nataniel Hernan , Ahmed Shahid Sattar , Wallace H. James , Sprague Brian L. , Ades Steven
Published: March 2023

358

Background: In a primary analysis of the STAMPEDE protocol, the addition of Abiraterone acetate to androgen deprivation therapy (ADT) in men with castration sensitive, high-risk, non-metastatic prostate cancer was associated with significantly higher rates of metastasis-free survival compared with ADT alone. However, the cost-effectiveness of Abiraterone in this population remains unaddressed. Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) associated with ADT with or without Abiraterone. This analysis was performed from a United States healthcare sector perspective. We estimated drug acquisition costs using the Federal Supply Schedule. Given current heterogeneity in prescription drug coverage, we used both brand-name and generic drug prices. The willingness-to-pay (WTP) threshold was $100,000 per QALY. Analyses were performed over the published STAMPEDE trial with median follow-up duration of 72 months. Model input parameters were based on the STAMPEDE trial data as well as best available and most recent data provided in the published literature. Sensitivity analyses explored uncertainty with regard to the model assumptions. Results: Using brand-name pricing, the addition of Abiraterone to ADT was associated with an increase in net costs by $217,616, and an increase in QALYS by 0.79. Therefore, the ICER associated with brand-name Abiraterone was $277,156 per QALY. Sensitivity analyses revealed that the monthly price of Abiraterone would need to be less than or equal to $2,581 in order to be cost-effective at a WTP threshold of $100,000 per QALY. In contrast, generic Abiraterone was associated with an increase in net costs by $45,325, and a cost-effective ICER of $57,726 per QALY. Conclusions: Abiraterone for high-risk non-metastatic prostate cancer is cost-effective using generic pricing. However, current brand-name pricing is roughly four times the threshold of cost-effectiveness, underscoring the need to increase access to generic drugs in the United States.
Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): Individual patient data meta-analysis from the MARCAP Consortium.
Authors: Ong Wee Loon , Wilhalme Holly , Millar Jeremy Laurence , Steigler Allison , Denham James William , Joseph David John , Roy Soumyajit , Malone Shawn , Nickols Nicholas George , Rettig Matthew , Valle Luca Faustino , Steinberg Michael L. , Sun Yilun , Zaorsky Nicholas George , Spratt Daniel Eidelberg , Kishan Amar Upadhyaya
Published: March 2023

366

Background: The kinetics of testosterone recovery (TR) vary following cessation of androgen deprivation therapy (ADT) of various durations when given in combination with radiotherapy for prostate cancer. Time to TR will impact on quality of life. We aim to identify factors affecting the time to TR following ADT use. Methods: We included trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone data is available. Time to non-hypogonadal TR (NHTR) (>8.0nmol/L) and time to full TR (FTR) (>10.5nmol/L) were estimated from the date of first available testosterone at trial enrolment to the date of TR using the Kaplan-Meier method. The effect of interactions between duration of ADT and patients’ age on TR was evaluated. Results: There were 1439 men with non-castrate testosterone at baseline (>1.7nmol/L) who met the inclusion criteria for analysis, of which 220, 765 and 454 men had 3-, 6-, and 18-months of ADT. There were 959 (67%) men who had FTR at last follow-up. For men who had 3-, 6-, and 18-months of ADT, the median time (range) to NHTR were 5.5 (1.6-76.3), 12.2 (0.8-53.6), and 30.1 (2.8-90.4) months respectively, while the median time (range) to FTR were 6.2 (1.8-75.7), 15.2 (0.8-86.0), and 36.0 (18.1-85.5) months respectively. In the subset of 1160 men who had normal testosterone at baseline (>10.5nmol/L), 851 (69%) men had FTR, with a median time (range) to FTR of 5.5 (1.8-75.7), 12.7 (1.8-86.0), and 30.8 (18.1-84.1) months for men who had 3-, 6- and 18-months ADT, respectively. For any given duration of ADT, men aged above 65 years were less likely to have FTR compared to those aged under 65 years – HR=0.67 (95%CI=0.46-0.99), HR=0.80 (95%CI=0.67-0.96), HR=0.64 (95%CI=0.51-0.81) for men who had 3-, 6-, and 18-months ADT respectively. There was no evidence of interaction between the effect of ADT duration on time to FTR and age (interaction P=0.3 for entire cohort). Conclusions: This is the largest pooled analysis of prospectively collected serial testosterone data from randomized trials, indicating substantial delay in FTR in men receiving longer durations of ADT. Approximately one-third of the men did not achieve FTR, which may have life-long impact on quality of life.
Access to care and health care quality metrics in urban versus rural patients (pts) with advanced prostate cancer (aPC).
Authors: Li Haoran , Sahu Kamal Kant Kant , Kumar Shruti Adidam , Mathew Thomas Vinay , Tripathi Nishita , Gebrael Georges , Sayegh Nicolas , Chigarira Beverly , Jo Yeonjung , Swami Umang , Gupta Sumati , Maughan Benjamin L. , Agarwal Neeraj
Published: March 2023

37

Background: Compared to the urban population, pts in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. Herein we aimed to compare the health care quality metrics and outcomes between pts with aPC from rural versus urban areas treated at a tertiary cancer hospital. Methods: In this IRB approved retrospective study, eligibility criteria were: presence of aPC, treatment at a single center (NCI-Designated Comprehensive Cancer Center (NCI-CCC), between 10/2017 to 9/2021). Rural-urban commuting area (RUCA) codes from the 2010 census /were used to classify the pts’ residences as urban (1-3) or rural (4-10) areas. The straight-line to distance of the pts’ place of residence from our institute was also calculated and included in the analysis. The median household income data were obtained and calculated from “The Michigan Population Studies Center”, based on individual zip codes. Results: A total of 994 pts were eligible and included (83.9% urban vs 16.1% rural). The baseline demographic profile and tumor characteristics were similar between the two groups. The median household income of pts from urban areas was higher by $8604/annum than that from rural areas (p<0.0001). There was no difference between urban versus rural pts in terms of receipt of lines of systemic therapies, clinical trial accrual, and receipt of tumor genomic profiling. No significant difference was found in the median overall survival between the two population (83.7 versus 92.8 months; p=0.14). Conclusions: These hypothesis generating data show that access to quality care, as available in an NCI-CCC can mitigate the disparities in the quality of health care delivery and clinical outcomes in urban versus rural pts with aPC. [Table: see text]
HDR brachytherapy and radiotherapy as salvage treatment for macroscopic recurrence in the prostate bed after radical prostatectomy.
Authors: Guix Benjamin , Panichi Marco , Garcia Ivan , Gonzalez Emma , Najjari Dina , Guix Ines , Costa Fernando , Sole Josep Maria , Guix Teresa , Quinzaños Luis
Published: March 2023

370

Background: To present early and late toxicity, biochemical, local, regional and distant control and survival in a prospective series of 75 patients with macroscopic local recurrence in the prostate bed after radical prostatectomy treated by salvage HDR brachytherapy. Methods: Between 12/1999 and 12/2020, 75 patients (pts) with exclusive macroscopic recurrence in the prostate bed after radical prostatectomy without nodal or distant metastases, were included in the study. Pts were prospectively treated by 46 Gy IMRT radiotherapy to the surgical bed followed by 16 Gy HDR brachytherapy in 2 implants of 8Gy each, one week apart and hormone therapy for 36 months. Rectal limitant dose was 85% and for urethra 115% of the prescribed dose. Toxicity was recorded according to the EORTC/RTOG criteria. Special attention to PSA levels, biochemical, local, nodal and distant metastases control and survival, as well as to quality of life was taken. Results: All pts completed treatment. No pts experienced grade 3 or higher rectal or urinary toxicity. odos los pacientes completaron el tratamiento. 2 pts presented G1 rectal toxicity (ocasional rectorragia) and 1 pts G2 rectitis (persistent rectorragia), that ceased with topic treatment (cortisone ointment) 1 Pts had G1 urethral toxicity (dysuria), that spontaneously disappeared qat few months no requiring any medical intervention. No patient developed stenosis, necrosis or urethral fistula during follow-up. With a median follow-up of 102 months, 13 pts had failure of the disease: 6 biochemical-only, 2 local recurrence, 2 pelvic recurrence, 1 paraaortic recurrence and 2 distant metastases. 2 patients died by the disease and 1 patient died by other cause (age related). Conclusions: IMRT plus HDR brachytherapy was a safe treatment without any early or late significant side-effect. Combined treatment by IMRT and HDR plus androgen deprivation was extraordinary effective in the control or macroscopic local recurrences in the prostatectomy bed after radical prostatectomy. Further studies are warranted.
Development and clinical validation of a novel biopsy-based six-gene signature to accurately risk-stratify men with early-stage prostate cancer to aid treatment decision making.
Authors: Krzyzanowska Agnieszka , Barron Stephen , Higgins Debra , Loughman Tony , Sheehan Katherine , Chan-Ju Wang Angel , Fender Bozena , McGuire Leah M , Galvin David Jonathan , O'Neill Amanda , Fay Joanna , O'Grady Anthony , O'Leary Des , Watson William , Bjartell Anders , Gallagher William M.
Published: March 2023

374

Background: Prostate cancer (PCa) is diagnosed in over 1.2 million men worldwide annually, making it the second-most common non-cutaneous cancer in men. Most men have indolent PCa and can safely defer treatment with active surveillance. However, many patients are commonly treated with surgery (radical prostatectomy, RP) or radiation therapy, which are associated with a significant reduction in quality of life. Molecular signatures have been developed to assist clinicians in stratifying patients based on their risk of aggressive PCa; while these have shown promise, there remains a significant opportunity for improving prognostic capacity. Methods: A panel of fourteen prognostic genes was identified from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. Gene expression was measured by reverse-transcription quantitative polymerase chain reaction in RP samples from an Irish cohort of men diagnosed with PCa and treated with RP (PCRC, n=426). Cross-validated logistic regression analysis identified a six-gene molecular risk score (MRS) with strong prognostic performance to predict aggressive PCa, i.e., adverse pathology (AP) at RP or biochemical recurrence (BCR). The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score to create a molecular plus clinical risk score (MCRS). The MRS and MCRS were clinically validated in biopsy samples from an independent Swedish cohort of men diagnosed with PCa and treated by RP (UPCA, n=100). Results: We identified a six-gene signature, consisting of four prognostic and two reference genes, with improved prognostic value over clinical features. In the clinical biopsy validation study univariable analysis, the AUC of the signature for AP was 0.72 (MRS) and 0.82 (MCRS) versus 0.72 for EAU risk categories and 0.82 for CAPRA. The C-index for BCR was 0.62 (MRS) and 0.74 (MCRS) versus 0.65 for EAU risk categories and 0.73 for CAPRA. Furthermore, in bivariable analysis, the six-gene signature added statistically significant (p < 0.001) prognostic value to EAU risk categories and CAPRA. Conclusions: The six-gene prognostic signature has strong performance for AP and BCR in an independent clinical biopsy validation study. MCRS can provide improved prognostic stratification and inform optimal patient management post-diagnosis.
Prediction of early prostate cancer recurrence using a liquid biopsy approach.
Authors: Rahbar Kambiz , Kidd Mark , Seitzer Konstantin Egon , Schrader Andres Jan , Boegemann Martin , Modlin Irvin Mark
Published: March 2023

386

Background: A critical clinical concern after radical prostatectomy for prostate cancer (PCa) is the timely identification of residual disease. Recurrent disease (biochemical recurrence: BCR) develops in approximately 30% of radical prostatectomies within 5 years of surgery. Currently, clinicopathological variables, including pathological tumor stage (pT-stage), Gleason score and PSA, or algorithmic combinatorial calculations (e.g., CAPRA-S) are used to predict BCR. Early and objective prediction of individuals at high risk of BCR would enable stratification of follow-up strategies and facilitate therapeutic therapy. To achieve these goals, we developed a liquid biopsy, the PROSTest, to identify PCa. This is a 27 multigene algorithmic signature with a high sensitivity and specificity (>90%) for PCa detection. We investigated if the PROSTest had utility as a predictive biomarker for BCR. Methods: Prospective recruitment of 60 PCa for radical prostatectomy with assessment of standard pathological, clinical and biomarker (PSA) data. D’Amico Risk scores and CAPRA-S were calculated. Blood was collected for PROSTest measurement pre-surgery. Target genes were amplified using qPCR and scored (0-100) using algorithmic analysis. Pre-surgical PROSTest scores were evaluated as predictors of BCR and compared with standard criteria as well as DR and CAPRA-S scores. Data was evaluated using Mann-Whitney U-test, multiple regression analyses, Kaplan-Meier survival analysis and Cox-proportional modeling. All data: median (range). Results: Consent was obtained in 48 (80%) patients. Median age (range) was 64 (50-82). Gleason was predominantly 7 (85%; 26: 7A, 15: 7B); TNM was primarily T2c (48%) and T3a (32%) with nodal disease evident in 8% and 0% cM1 disease. Resections were R0 (85%) and 7 R1. The median follow-up was 42 days (range: 14-782). Early BCR occurred in 8 (17%) patients. This included 3/7 (43%) of R1 and 5/41 (12%) R0 resections. PSMA imaging confirmed 3 LN recurrences and new visceral ( n=1) and bone ( n=1) disease. D’Amico Risk scores were mostly “high” (88% with risk score ≥50%) and were not associated with early BCR. CAPRA-S scores were higher in those who developed early BCR (5: 1-9) than in those who did not (2: 0-5). Pre-surgical PROSTest scores were elevated in all (median 59: 15-81). Multiple regression analysis identified only PROSTest score ≥60 and nodal status were associated with BCR. The median Recurrence Free Survival (mRFS) was 89 days compared to undefined in those with baseline PROSTest scores ≥60 (HR: 9.7; 95%CI: 2.16-43.7; p=0.003). No recurrences were identified in those with scores <60. Conclusions: Early biochemical recurrence (within 3 months of surgery) can be accurately predicted by elevated (≥60) pre-surgical PROSTest blood gene expression scores. This suggests the marker could be used as a stratification tool for neoadjuvant therapy, or to guide the frequency of monitoring during follow-up.
Use of IsoPSA with prostate MRI PIRADS score in biopsy decision making in patients with elevated PSA.
Authors: Benidir Tarik , Lone Zaeem M , Abdallah Nour , Wood Andrew , Campbell Rebecca , Purysko Andrei , Nguyen Jane , Klein Eric A. , Abouassaly Robert , Campbell Steven , Weight Christopher J.
Published: March 2023

388

Background: IsoPSA is prospectively validated to be superior to PSA and percent free PSA in predicting prostate cancer (PCa) as well as clinically significant prostate cancer. We sought to evaluate the use of IsoPSA in combination with prostate magnetic resonance imaging (MRI) and the prostate imaging reporting and data systems (PIRADS) on predicting either benign/indolent or csPCA at biopsy. Methods: This was a single center retrospective review of prospectively collected patient data that included all patients who underwent IsoPSA testing, preoperative prostate MRI and prostate biopsy from 2019-2021. Chi Squared analysis was used to assess for associations between a binary classification of low (<6) or elevated (>6) IsoPSA index, in combination with PIRADS scores in predicting either indolent/benign or csPCa at biopsy. Logistic regression was used to explore independent predictors of csPCa. Receiver Operating Curve (ROC) analysis was completed with areas under the curve (AUC) for IsoPSA and PIRADS scores, both alone and in combination. Predictive probabilities were assessed using combinations of IsoPSA thresholds and PIRADS scores. Results: 207 patients met inclusion criteria. Among patients with a negative MRI, low IsoPSA index was associated with a lower chance of csPCa compared to those with elevated IsoPSA (2% vs 15%, p<0.018). For those with a PIRADS 4-5 lesion, elevated IsoPSA index was associated with a higher chance of csPCa at biopsy compared to a low IsoPSA index (49% vs 19%, p=0.05). On multivariate analysis, elevated IsoPSA and PIRADS 4-5 were independent predictors of csPCa (p<0.001). Similarly, low IsoPSA index and negative MRI were independent predictors of benign/indolent disease at biopsy (p<0.001). Using predictive probabilities, the combination of PIRADS 4-5 with elevated IsoPSA was associated with the highest risk of csPCa (48%) and the highest AUC (0.83) for predicting csPCa. This AUC value was superior to either marker alone (0.76, 0.76) and total PSA alone (0.57) (p<0.001). Conclusions: The combination of elevated IsoPSA with adverse PIRADS score (4-5) is associated with a 48% predicted probability of csPCa at biopsy with an AUC of 0.83, which was more accurate than either marker alone. A low IsoPSA in combination with a negative MRI resulted in a 98% chance of benign/indolent disease at biopsy. These findings may prove useful for the practicing Urologist and may help guide discussions regarding the need for biopsy when interpreting various IsoPSA/PIRADS combinations. [Table: see text]
Testicular radiomics correlated with pathology at time of post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumor.
Authors: Taylor Jacob , Venishetty Nikit , Xi Yin , Howard Jeffrey , Ng Yee Seng , Bagrodia Aditya
Published: March 2023

413

Background: Testicular germ cell tumors are the most commonly diagnosed malignancy in men aged 20 to 39 years old. Up to a third of patients will have metastatic disease at presentation typically managed with upfront chemotherapy. For many patients with metastatic non-seminomatous germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is performed to further stage and treat residual disease in the retroperitoneum. Although 50% of patients will have viable GCT or teratoma, we do not have accurate tools to predict pre-operatively which patients will have residual disease after chemotherapy. Testicular radiomics is an emerging field that collects complex quantitative tumor imaging data from conventional imaging to aid in clinical decision making. Our aim was to use testicular radiomics data to predict pathology after PC-RPLND. Methods: We extracted radiomics data on 45 patients with metastatic NSGCT undergoing PC-RPLND from 2008-2019. Clinical and pathologic data were collected. Regions of interest (ROI) around metastatic nodes were drawn by a dedicated abdominal radiologist. PyRadiomics, an open-source imaging extraction software, was used to extract first order, shape, and second order statistics from each ROI. Multiple t-tests of testing difference in radiomic features between binary pathology type were performed. P values were adjusted using the BH method to control false discovery rate. Boxplot of features with adjusted p value < 0.05 were shown. Radiomic feature extraction was done in python 3.7 and statistical analyses were done in R 4.2.0. Results: There were 16 (36%) clinical stage II patients and 28 (62%) clinical stage III. 19 (42%) patients had necrosis on PC-RPLND pathology, while 24 (53%) and 2 (4%) patients had teratoma and viable germ cell tumor, respectively. First order statistics mean, median, 90th percentile and root mean squares were significant. Strong correlations were observed between these four features and a lower signal was associated with positive pathology (Table). No significant difference was observed in other first order, shape, or texture features. Conclusions: Testicular radiomics is an emerging tool that has the potential to help predict which patients with metastatic NSGCT are at higher risk of persistent disease after chemotherapy. This study found relatively few first order radiomic data that were correlated with post-operative pathology. Further precision of extraction of the radiomics data may improve clinical decision-making in patients with metastatic NSGCT after chemotherapy prior to RPLND. [Table: see text]
High-dose chemotherapy with autologous stem cell transplant (HDCT) for patients (pts) with advanced germ-cell tumors (aGCT): Real-world evidence from a tertiary cancer center in Brazil.
Authors: Polho Gabriel Berlingieri , Cunha Mateus Trinconi , Xavier Erick Menezes , Silva Jamile Almeida , Hidalgo Filho Cassio Murilo Trovo , Crusoé Nathália de Souza Del Rey , Atanazio Marcelo Junqueira , Horita Vivian , Fialho de Freitas Guilherme , Muniz David Queiroz Borges , Geraldo Rocha Vanderson , Mota Jose Mauricio
Published: March 2023

414

Background: HDCT is a potentially curative treatment for pts with aGCT after conventional-dose chemotherapy (CDC). There is scarce evidence of outcomes from aGCT pts treated with HDCT in low and middle-income countries. Methods: We reviewed our institutional database to identify pts with progressive aGCT referred for HDCT following tumor boards. Medical charts were analyzed to extract clinical data. Log-rank was used to compare survival estimates and Cox proportional hazard to determine effects on overall survival (OS). Exploratory correlation and survival trend analysis used synthetic minority oversampling and Spearman’s rho estimated correlations. Results: From 1/2013 to 8/2022, 35 aGCT pts were referred for HDCT. Median age was 28 years (IQR 25-30). Most pts had testicular primary (84%), non-seminoma histology (87%), 1 prior treatment line (62%), poor-risk by IGCCCG (78%), and intermediate to very high-risk by IPFSG (45%). Of these, 32 pts were deemed eligible after initial evaluation, 25 had mobilization chemotherapy, and 21 received ≥1 cycle of HDCT. Reasons for treatment non-fulfillment included progressive disease and/or performance deterioration due to toxicity. HDCT regimen varied, with most pts receiving TI-CE (62%). Most pts had delays ≥1 month (85%) and ≥2 months (52%) in the scheduled treatment. The 1-year and 2-year OS rates were 42% and 38% in the eligible population, while 70% and 62% among those who had ≥ 1 cycle HDCT. No risk factors correlated with OS in the univariate analysis (Table). Exploratory analysis of oversampled pts treated with ≥1 cycle of HDCT showed correlation of poor IGCCCG (p<0.01) and IPFSG (p=0.03) with OS. Time to mobilization (TTM) was larger in poor-risk IGCCCG pts (0.4 vs. 1.7 months, p<0.01). Four deaths were attributed to HDCT. Conclusions: HDCT was feasible at our tertiary center in Brazil, despite some treatment-related deaths. For pts who had at least 1 HDCT cycle, survival outcomes were similar to the established literature. Significant delays in protocol were noted and correlated with prognostic group risk. [Table: see text]
Impact of age on the therapy-related characteristics and outcomes of testicular germ cell tumors at a tertiary care center in India.
Authors: Pathak Neha , Kumar Sudhir , Raj Abhishek , Sahoo Ranjit Kumar , KP Haresh , Singh Prabhjot , Shamim Shamim Ahmed , Seth Amlesh , Ray M D , Kaushal Seema , Das Chandan Krushna , Batra Atul
Published: March 2023

415

Background: Testicular germ cell tumors (t-GCTs) commonly present in age group 20-40 years (yrs). Older patients (pts) in many cancers have worse tolerance to therapy and outcomes. We examine herein the effect of older age in t-GCT pts. Methods: We conducted a chart-review-based retrospective analysis of pts of t-GCTs diagnosed and treated at our urogenital clinic from 2015-2021. Pts were divided into two groups: Age ≤40 years (Group A) and >40 years (Group B). Multivariable Cox regression models were constructed to analyze the prognostic value of older age while adjusting for measured confounders. Results: A total of 298 patients of t-GCT were identified; the median age was 30 yrs (interquartile range 24-37), 43.0% with intermediate or poor risk, 64.8% patients with non-seminomatous GCT (NSGCT), 250 pts in gp A and 48 in gp B. Baseline characteristics in both gps differed significantly with respect to the risk category, and seminoma histology, while there was no difference for performance status (ECOG ≥2), see table. Bleomycin, cisplatin, and etoposide (BEP) was the most common chemotherapy (226/262 pts), and use of BEP was not different in 2 gps (p=0.249). Grade III/IV adverse effect burden was greater in gp B vs gp A for febrile neutropenia, nausea/vomiting, and diarrhea, while infertility was more in gp A (Table). Outcomes in terms of markers normalization (163 vs 33, p=0.408) and radiological response (complete remission, 93 vs 20, p=0.205) did not differ. Median overall survival was not reached in both gps, and the hazard ratio for age >40 yrs was 1.91 (95% confidence interval 0.91-3.99, p =0.086), after adjusting for risk category, performance status, and response to therapy. Conclusions: Age does not deter the use of platinum-based therapy, which, although more toxic, has similar efficacy to younger pts of t-GCT. [Table: see text]
POMB/ACE, a cocktail of 7 drugs to treat intermediate to poor prognosis and high volume germ cell cancers: A large retrospective study.
Authors: Howlett Sarah , Reid India , Gogbashian Andrew , Devine Rebecca , Charalambous Linda , Agarwal Samita , Sharma Anand
Published: March 2023

419

Background: Patients presenting with intermediate and poor risk germ cell tumours tend to be young and fit. Although more than half of patients may hope to be cured, a proportion will die because of their cancer. An aggressive strategy is required to maximise the chance of cure. Alternating high dose chemotherapy regimens have been trialled with varying outcomes. We present real world data demonstrating the efficacy and safety of first-line POMB/ACE (Cisplatin, Vincristine, Methotrexate, Bleomycin alternating with Actinomycin D, Cyclophosphamide, Etoposide) for these patients. Methods: 40 metastatic germ cell patients treated with POMB/ACE were identified at our centre. Patients were classified as being in intermediate or poor prognostic groups based on the International germ cell cancer collaborative group classification (IGCCCG). Treatment was administered every 2 weeks for up to 7 cycles. Response to treatment was determined by radiological imaging and serum tumour markers. Toxicities were evaluated using CTCAE version 5.0. Results: Clinical characteristics were as follows: median age at diagnosis 32 years (range 18-69). 36 patients (90%) were male and 4 patients (10%) were female. 29 (73%) presented with poor risk disease and 11 (27%) with intermediate risk. Patients completed between 1 and 7 cycles of POMB/ACE with the median number of cycles being 5. Data on toxicity severity was collected where available. This is summarised in the table. One grade 4 event was noted. 10 patients experienced grade 3 toxicities. Interestingly no patients were reported to develop bleomycin lung toxicity. This may be due to bleomycin being omitted in patients felt to be at higher risk of lung toxicity (smokers, older patients, pre-existing lung conditions). 30 (75%) patients were progression free following POMB/ACE. 9 (22%) patients went on to have subsequent systemic chemotherapy regimens and high dose stem cell transplant (HDSCT), as they had high volume disease, and persistent marker positive disease. 16 (40%) patients went on to have further surgical interventions, most commonly retroperitoneal lymph node dissection (RPLND), no active malignancy was seen in the resected specimen. At a median follow-up of 43 months, 39 (97.5%) of patients are still alive. Conclusions: POMB/ACE is a safe and effective regimen for patients presenting with intermediate to poor risk germ cell tumours. Patients with high volume disease should be considered for subsequent HDSCT to achieve better outcomes. [Table: see text]
Robotic retroperitoneal lymph node dissection: A systematic review and meta-analysis of perioperative outcomes.
Authors: Garg Harshit , Mansour Ahmed M , Psutka Sarah P. , Kim Simon P , Porter James , Gaspard Christine S , Dursun Furkan , Pruthi Deepak K , Wang Hanzhang , Kaushik Dharam
Published: March 2023

420

Background: Retroperitoneal lymph node dissection (RPLND) forms an integral part of the management of testis cancer. Robotic RPLND (R-RPLND) is a minimally invasive treatment option for this disease. This systematic review assessed the safety and feasibility of R-RPLND and compared the perioperative outcomes of R-RPLND with open RPLND (O-RPLND). Methods: The PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND. Results: The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4,224 patients (single-arm studies, n=461; comparative studies, n=3,763). Of 461 patients in the single-arm studies, 271 underwent primary R-RPLND and 190 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175-540 minutes and the major complication rate was 3.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134-550 min and the major complication rate was 8.4%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 8.9% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, p=0.0001) and a lower complication rate (18.5% vs 7.8%, p=0.002; Table). Conclusions: R-RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated. [Table: see text]
Relapse-free and overall survival in patients with non-seminomatous testicular germ cell tumours with teratoma-free primaries.
Authors: Paffenholz Pia , Landwehr Georg , Seidel Christoph Alexander , Poch Annika , Bokemeyer Carsten , Cathomas Richard , Pongratanakul Pailin , Hiester Andreas , Albers Peter , Pichler Martin , Krege Susanne , Syring Isabella , Heinzelbecker Julia , Nestler Tim , Pfister David , Heidenreich Axel
Published: March 2023

421

Background: Characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate. Methods: We performed a retrospective analysis including 557 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". Results: Of the eligible 557 patients with NSGCT, 237 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 320 (58%) were teratoma-free. Teratoma-containing primaries had a significantly higher clinical stage (p=0.002) and worse prognosis (p=0.051) compared to teratoma-free specimens. Lymph node metastasis were significantly larger before (4.5 vs 2.5cm; p<0.001) and after chemotherapy (3.5 vs 2.5 cm; p<0.001) in teratoma-containing primaries. Post-chemotherapy retroperitoneal lymph node dissection was performed in 57% of all patients. As teratoma-containing specimens revealed a significantly lower number of complete responses after chemotherapy, PC-PRLND was more often performed, with teratomatous elements being more often present in the PC-RPLND specimens compared to non-teratoma containing primaries. Kaplan-Meier estimates revealed that 19% of all patients relapsed during a median follow-up of 56 months [29-112] with a median time to relapse of 10 months. Teratoma-containing had a significantly lower relapse-free survival (RFS) compared to teratoma-free NSGCT (relapse rate 24% vs 16%, p=0.020). 8% (45/533) of all patients died due to their disease. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (8% vs. 9%, p=0.563), however median overall survival was not reached. Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly higher clinical stage and worse prognosis at time of presentation compared to teratoma-free primaries. Furthermore, patients with teratoma-containing primaries showed a significantly worse relapse-free survival. Consequently, treating physicians should be aware of these patients portending a dismal prognosis and the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.
Primary mediastinal seminoma: Treatment and survival outcomes.
Authors: Hassoun Rebecca , Althouse Sandra K. , King Jennifer , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil
Published: March 2023

422

Background: Primary mediastinal pure seminoma is a rare entity and there is no clear consensus for optimal management. We report treatment and survival outcomes of patients with primary mediastinal seminoma evaluated at our institution. Methods: The Indiana University (IU) testicular cancer database was queried for patients with primary mediastinal seminoma. 21 patients evaluated at IU between 1994-2022 were included in this analysis. Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) analysis. Results: Median age at diagnosis was 40.7 (range, 19.4-54.2). 18 (85.7%) patients were IGCCCG good risk and 3 (14.3%) were intermediate risk. Median pre-chemotherapy hCG was 10.3 (range, 0.6-1500). 12 (57.1%) patients had metastatic disease. Metastatic sites included mediastinal/supraclavicular lymph nodes in 9 patients (42.9%), lungs in 3 (14.3%), retroperitoneal lymph nodes in 3 (14.3%), brain in 1 (4.8%), liver in 1 (4.8%), adrenal gland in 1 (4.8%), kidney in 1 (4.8%) and bone in 1 (4.8%). First-line chemotherapy was BEPx3 in 9 (42.9%) patients, EPx4 in 4 (19.0%), BEPx4 in 3 (14.3%), BEPx3 + EPx1 in 2 (9.5%), VIPx4 in 2 (9.5%), and VIPx1 + BEPx3 in 1 (4.8%). With a median follow-up of 4.65 years from first-line chemotherapy start date, 3 (14.3%) patients progressed after first-line chemotherapy. Among patients who progressed, salvage 2nd line therapy was high-dose chemotherapy in 1 patient. 1 patient received more than 2 lines of therapy. 1 patient underwent surgical resection of residual mediastinal mass due to concern for local progression, with pathology revealing necrosis only. The 5-year progression-free survival (PFS) from first-line chemotherapy was 82.4% (95% CI 54.7-93.9). The 5-year overall survival (OS) was 94.1% (95% CI 65.0-99.1). At last follow-up, 20 (95.2%) patients had no evidence of disease, and 1 (4.8%) was dead of disease. Conclusions: Patients with primary mediastinal pure seminoma have high cure rates with risk adapted cisplatin-based combination chemotherapy. Despite residual masses, further surgical resection or radiation is not required in the vast majority of these patients and these residual masses can be safely monitored with surveillance.
Evaluation of miRNA-371a-3p (miR371a) assay to predict final pathohistology in patients undergoing primary nerve-sparing retroperitoneal lymphadenectomy (nsRPLND) for stage IIA/B seminomas and non-seminomas.
Authors: Seelemeyer Felix , Pfister David , Paffenholz Pia , Merkelbach-Bruse Sabine , Pappesch Roberto , Heidenreich Axel
Published: March 2023

427

Background: NS-RPLND represents a guideline recommended treatment option in marker negative low volume metastatic seminomas and nonseminomas (NSGCT). However, about 30% of clinical stage IIA patients demonstrate equivocal findings of uncertain dignity so that they might undergo unnecessary treatment. Elevated serum concentrations of the molecular marker miR371 have been reported to correlate with the clinical stage even in small volume metastases. It was the purpose of our pilot study to evaluate the predictive accuracy of miR371 in a cohort of patients who underwent nsRPLND for clinical stage IIA/B germ cell tumors of the testis. Methods: Between 1-9/2022, 16 patients with marker negative clinical stage IIA/B seminomas (n=10) and NSGCT (n=6) underwent primary nsRPLND with a modified template resection via an open surgical approach. Blood specimens (20ml) were drawn on the day immediately prior to surgery and processed according to the manufacturer’s protocol. miRNA is extracted and purified with the Maxwell RSC MiRNA Plasma and Serum Kits prior to its transcription into cDNA using cDNA Solution, Reverse Transcriptase and RNase Inhibitor. Subsequently, this cDNA is amplified. Using qPCR techniques, the miRNA 371a is quantified using Roche Lightcycler 480 II. Using the Lightcycler software, the median Cp (CP = crossing points) of the triplicates is calculated and converted into a RQ value (RQ= relative abundance). Results: nsRPND was performed in all patients without significant Clavien-Dindo IIIa-V complications. Mean OR time was 131 (105-195) minutes, mean blood loss was < 150ml, transfusion rate was 0%. Mean number of dissected lymph nodes was 17 (7-32), mean diameter of positive lymph nodes was 2.1 (0.8-4.1) cm. Histology revealed metastatic seminoma or nonseminoma in 12/16 (75%). In 4 patients histology revealed non-malignant disease (n=2), teratoma, and lymphoma. miR371 was positive in all 12 (100%) pts with metastases and it was negative in 3/4 (75%) pts without metastases. One patient with small volume CS IIA seminoma was false negative. Conclusions: This is the first report to demonstrate that miR371can be used as a personalized and individual biomarker to predict the presence of small volume retroperitoneal lymph node metastases in CS IIA/B seminomas and in nonseminomas. Patients with positive findings should undergo active treatment whereas negative findings should result in close follow-up. Date are currently validated in a multi-institutional trial.
Who coauthors Cochrane Reviews related to genitourinary cancers? A 1998-2022 analysis of country and gender diversity.
Authors: Mirza Sahaam , Ozair Ahmad , Kumar Abhishek , R Subash Nishanth , Mirza Moben
Published: March 2023

436

Background: Women and individuals from low- and lower-middle-income countries (LMICs) are under-represented in urology literature, particularly in high-impact publications. Cochrane, a non-profit collaboration, publishes high‐quality systematic reviews that frequently impact policy and clinical practice worldwide. However, the state of the country and gender diversity amongst authors of urology-related Cochrane Reviews is unknown, which this work sought to determine. Methods: We searched the Cochrane Database, under the filter “Topic: Urology”, for all reviews related to genitourinary cancers, published until 25 July 2022, including both active reviews and those withdrawn for updation. We extracted authorship data and classified the national affiliation of authors into either high- and upper-middle-income countries (HICs) or LMICs based on the World Bank income classification. We treated a collaborative author group belonging to one country as a single-country affiliation. Given the higher accuracy of manual web searches for ascertaining gender over algorithmic estimation, we utilized the former to achieve ≥90% ascertainment. We endeavored to capture at least one webpage that demonstrated their gender, e.g. institutional profile, Google Scholar, ResearchGate, etc. Results: A total of 54 urology-related reviews, co-authored by a total of 324 authors, were included. 53 reviews were published by the Cochrane Urology Group, while one review was by the Incontinence Group. Zero authors were from LMICs. Countries with the highest representation of co-authors were the US (24.1%), UK (25.3%), Germany (23.5%), South Korea (6.8%), Australia (6.2%), Netherlands (3.7%), China (2.8%), Canada (2.5%), Brazil (1.5%). Gender could be ascertained for 94.14% (N=305/324) of co-authors. Women made up 27.5% (N=84/305) of co-authors, 16.0% (N=8/50) of first authors, and 16.89% (N=9/53) of corresponding authors. Conclusions: Women are well-represented in Cochrane Reviews related to genitourinary cancers compared to urology-specific journals and their representation in urology. However, LMICs contributed zero authors, while those from the US, UK, and Germany constitute >70% of authors for one of the highest-quality evidence sources in urology. Equitable authorship representation may help expand both the utilization and the global relevance of recommendations of such high-impact urology literature. Global capacity-building efforts are warranted, particularly in Africa, for enhancing the involvement of LMIC urologists with evidence synthesis.
Survey of keratin 17 (K17) expression in different urothelial malignancies.
Authors: Ecke Thorsten , Wirtz Ralph M. , Barth Gregor , Koch Stefan , Jahanfard Sholeh , Kim Nam W
Published: March 2023

458

Background: The current non-invasive urine tests tend to display low sensitivity for the detection of urothelial cancers, especially in low-grade cancer. Recent reports suggest that the URO17 test based on the Keratin 17 (K17) biomarker displays high sensitivity and specificity in the detection of urothelial carcinoma in both low-grade and high-grade cancers and show promise as an effective non-invasive test for bladder cancer. The current study aimed to evaluate K17 expression in different histological categories of urological diseases. Methods: Ninety-five urine specimens were collected from 2020-2021 that represented 19 different histological categories of urothelial diseases. These samples were prepared onto slides and tested with the URO17 Bladder Cancer test (KDx Diagnostics Inc.) on DAKO Link48 autostainer using the manufacturer’s recommended procedures. The stained samples were evaluated by a cytopathologist and scored using five K17-positive urothelial cells as a cut-off. Results: K17 was positive in 20/20 (100%) of the urothelial carcinoma, and 23/27 (85%) of Non-invasive papilloma and urothelial carcinomas. K17 was positive in 100% of carcinoma in situ, papillary urothelial carcinoma, sarcoma, and small cell carcinoma, papillary urothelial carcinoma, urothelial papilloma, inverted papilloma, renal-pelvis urothelial carcinoma, and urothelial carcinoma with squamous differentiation. K17 was also expressed in many cystitis, inflammatory myofibroblastic tumors, and PUNLMP, but not in prostate carcinoma. In 19/22 cases (86%) K17 was mostly positive in urine samples from patients with prior history of bladder cancer, but were histologically determined to be benign. The overall sensitivity of K17 in the cancer group was 88.5% (54/61 positive) with K17 being expressed in both high-grade and low-grade cancers. Of the seven false-negative samples, five were low-grade, one was high-grade, and one was from the inflammatory myofibroblastic tumor. Conclusions: Keratin 17 is highly expressed in almost all cases of urothelial carcinoma including those of papillary and squamous characteristics, confirming the high sensitivity of K17 in detecting all categories of urothelial carcinoma. Keratin 17 was also observed in many benign and premalignant conditions such as cystitis, PUNLMP, and metaplasia suggesting the K17 expression can result from a trauma to urothelium that could lead to activation of K17 in regenerating urothelial cells. Additional studies are ongoing to confirm and expand the utility of the K17 biomarker in bladder cancer.
FDG PET-CT imaging in assessing interim response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle invasive bladder cancer (MIBC): A prospective study.
Authors: Sridhar Srikala S. , Power Nicholas , Breau Rodney H. , Cheng Susanna Y. , Pond Gregory Russell , Chung Peter W. M. , Metser Ur , Levine Mark Norman , Mukherjee Som D.
Published: March 2023

460

Background: Muscle invasive bladder cancer (MIBC) is an aggressive local disease where initial staging with conventional CT imaging is often suboptimal. To explore the role of PET-CT in both staging MIBC and assessing response to neoadjuvant chemotherapy (NAC), we conducted a prospective multicentre, randomized trial known as PETMUSE. We report here the first results from the neoadjuvant substudy which assessed interim PET-CT response after 2-3 cycles of NAC and how this correlated with disease free survival (DFS) and overall survival (OS). Methods: Patients with MIBC (T2a-4a, N0-3, M0) based on transurethral resection of their bladder tumor and CT staging were randomized 2:1 to PET-CT or no PET-CT. All PET-CT patients, receiving cisplatin-based NAC underwent a second PET-CT after 2 cycles of gemcitabine and cisplatin (GC) or 3 cycles of dose dense methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) to assess for interim response. Patients were scored (1-5) by 2 independent reviewers according to the extent of metabolic response on PET-CT. Disease-free survival (DFS) and overall survival (OS) were collected. Results: Between 2016 and 2021, 291 patients were enrolled on PETMUSE of which 46 participated in the neoadjuvant substudy. Median age was 68 (51-86); 36 (78%) were male; 26 were ECOG 0 (57%); 31 (68%) were T2, 13 (28%) were T3/T4; and 35 (76%) were node negative. In terms of NAC regimens: 22 (48%) received GC, 17 (37%) split dose GC, 6 (13%) ddMVAC, and 1 (2%) MVAC. On PET-CT, 23 (50%) had a complete metabolic response, 14 (30%) had a partial metabolic response, 5 (11%) had no change or mixed response and 4 (9%) had progressive disease or new lesion on PET scan. Metabolic response on PET-CT was a statistically significant prognostic factor for both DFS and OS (see Table). Conclusions: In MIBC patients receiving cisplatin-based NAC, metabolic response seen on interim PET-CT was correlated with DFS and OS. PET-CT warrants further study in this setting as a potential early indicator of response to NAC. Clinical trial information: NCT02462239 . [Table: see text][Table: see text]