bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemcitabine/paclitaxel/adriamycin (GTA) as a nephron-sparing regimen in urothelial carcinoma: The MD Anderson Cancer Center (MDACC) experience.
Authors: Moussa Mohammad Jad , Subramanian Naveen G. , Haro-Silerio Jaime , Chen Lily , Shah Amishi Yogesh , Gao Jianjun , Corn Paul Gettys , Goswami Sangeeta , Msaouel Pavlos , Wang Jianbo , Kamat Ashish M. , Guo Charles C. , Tannir Nizar M. , Siefker-Radtke Arlene O. , Alhalabi Omar , Campbell Matthew T
Published: June 2024

e16576

Background: GTA (Gemcitabine 900 mg/m2 IV; Paclitaxel 135 mg/m2 IV and Adriamycin 30 mg/m2 IV, with pegfilgrastim 6mg SQ on a 14-day cycle) was initially reported from a prospective phase II study of 39 patients (pts) by Siefker-Radtke et al. Urology (2016). We report real-world efficacy and survival outcomes with this nephron-sparing regimen in locally advanced or metastatic urothelial carcinoma (LA/mUC). Methods: We retrospectively reviewed records of n=76 pts with frontline (1L) GTA for LA/mUC between March 2016 and April 2023 at MDACC. Imaging-based best overall responses (BOR) using RECIST v1.1 were noted as partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). We use Kaplan-Meier (KM) method to estimate overall survival (OS) and progression-free survival (PFS) from GTA start, and reverse KM for follow-up (FU). Results: Baseline characteristics (n=76) are shown in Table. Median age at diagnosis was 70.6 [IQR: 65.3 – 76.3]. The decision to start GTA was justified by tumor-related (55, 72.4%) or non-tumor-related (14, 18.4%) renal insufficiency, and general comorbidities (7, 9.2%).n=48 (63.2%) had percutaneous nephrostomy or ureteral stenting before GTA initiation. Pts had a median number of 3 cycles (IQR: 2-5). At GTA start, most pts (38, 50%) had one Barjorin risk factor (either bone/liver/lung mets or ECOG PS ≥2), 28 (36.8%) had none and 10 (13.2%) had both factors. Median OS was 11.3 mo (95% CI: 9.1 – 15.1 mo) with a median FU of 64.8 mo (95% CI: 26.2 – 83.6). Median PFS was 3.4 mo (95% CI: 3.03 – 4.5 mo). Overall response ratewas 26.3%, and BOR to 1L GTA included: PR 20/76 (26.3%), SD 25/76 (32.9%), PD 17/76 (22.4%) and NE 14/76 (18.4%). NE responses were due to transition to cisplatin-based regimens or other therapies in 8/14, toxicity in 3/14, pt death in 2/14 and pt preference in 1/14. GTA dose reduction was required in 15 (19.7%), and serious adverse events leading to hospitalization occurred in 18 (23.7%). Finally, among 69 pts with tumor or non-tumor related renal insufficiency, 16/69 (23.2%) were able to receive cisplatin post-GTA. In a paired t-test analysis of 76 GFR pairs, an improvement in GFR post-GTA was observed compared to pre-GTA GFR, with a significant difference of 11.2 mL/min [95% CI: 7.4 – 14.9, p < 0.0001]. Conclusions: GTA shows modest efficacy as a 1L regimen in LA/mUC. The facilitation of cisplatin-based regimens after GTA in a subset of pts might be explained by restoring patency in partially obstructed collecting systems. This ‘GTA bridging’ strategy may be beneficial for pts for whom nephrostomy or ureteral stenting proves impractical or insufficient to address renal insufficiency. [Table: see text]
Comparison of clinical outcomes of bladder preservation and surgery in a real-world study of patients with muscle invasive urothelial carcinoma using urine and plasma based MRD (minimal residual disease) assays.
Authors: Au Cherry , Tan Alan
Published: June 2024

e16580

Background: Recently, non-invasive urine/plasma-based minimal residual disease (MRD) assays have demonstrated the ability to reliably detect deep molecular alterations in bladder cancer patients. Similar to circulating tumor DNA, urinary tumor DNA (utDNA) is a noninvasive method of measuring MRD by evaluating the molecular landscape of tumor DNA shed in urine with next generation sequencing techniques. UtDNA can reflect the tumor landscape in real-time in patients with urothelial carcinoma via direct shed into the urine and can be utilized in monitoring for disease progression and also treatment response. This study investigates tissue-informed blood MRD and urine-informed urine MRD tests in the real world setting. Methods: A cohort of 40 real-world bladder and UTUC patients were included in this study. Treatment modalities such as neoadjuvant chemotherapy, trimodality therapy (TMT) for bladder preservation, and systemic chemotherapy/immunotherapy were utilized. Matching time point blood samples and urine samples were collected at variable intervals depending on the treatment regimens the patients received. Urine samples were tested using the PredicineBEACON urine MRD assay, which used the urine PredicineWES+ whole exome sequencing results from baseline urine samples for the design of a personalized MRD panel. Patients were followed up with MRD tests until otherwise censored. Results: There were a total of 94 urine and 253 plasma-based MRD tests with a success rates of over 90%, indicating the maturation of liquid biopsy lab technologies. Patients were followed for a median of 6.5 months between the first MRD assay and most recent follow up. MRD status and tumor fraction (TF) were monitored. The TF and kinetics from the urine MRD assay were in high concordance with the blood MRD assay results at matching time points. The mutation allele frequency time course changes matched with patient treatment responses and progression events in most cases. Clear increase in mutations and TF were observed in patients with progressive disease. Patients receiving definitive therapy had good disease-free survival time (longest >2 years), and there is no significant difference between bladder preservation or surgery-based intervention. Conclusions: In this study, we observed no significant difference in clinical outcomes between bladder cancer patients receiving bladder preservation or surgery-based intervention. Urine and blood-based MRD tests closely correlated with clinical outcomes. Our study emphasizes the value of serial monitoring of urine/plasma-based MRD assays in informing MRD status or treatment response for patients who undergo bladder preservation or cystectomy. The number of cases was limited in this study and further follow up will be needed to confirm the findings in this study.
Neoadjuvant cisplatin-based chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of the bladder: Post hoc analysis of two prospective studies.
Authors: Kim Min Jung , Cho Sung Wook , Lim Sung Hee , Park Se Hoon
Published: June 2024

e16583

Background: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies (Sung HH, Investig Clin Urol 2022; Kim H, Cancer Res Treat 2023) was performed to better evaluate the feasibility of selective bladder preservation CRT. Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine/cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n = 20), metastatic only (n = 16), and both (n = 7). In 27 patients with intravesical recurrence, transurethral resection and BCG treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% CI, 25.1-67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (HR, 0.465; 95% CI, 0.222-0.976). Conclusions: The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.
Bacillus Calmette-Guerin (BCG) utilization and treatment (Tx) patterns in Chinese patients (pts) with non-muscle invasive bladder cancer (NMIBC): Results from a national urologist survey.
Authors: He Wang , Zhuang Suili , Liu Zhenhua , Jia Lifang , Mao Huirong , Huang Jian
Published: June 2024

e16587

Background: China has the highest annual incidence (>85,694 new cases) and mortality (>39,393 deaths) from bladder cancer of any country; NMIBC is the most common subtype and is associated with a high risk of recurrence and progression. While intravesical BCG following transurethral resection (TURBT) is effective for NMIBC, there are limited real-world data on patient characteristics, BCG use and factors informing Tx decisions in China. Methods: We performed a cross-sectional, questionnaire-based survey of 300 urologists with experience of administering BCG for NMIBC from 13 cities and 10 provinces across China. Here, we summarized patient characteristics, urologists’ approach to risk assessment, BCG use and Tx patterns. Net Importance Score (NIS) was defined as the percentage of urologists who stated a factor was important (6–7 on a scale from 0–7) minus those who did not (1–4/7). Results: Pts with NMIBC had a median age of 59.6 years, 73% were male, 33% had a low annual household income (≤100,000 CNY [~13,700 USD]), 19% had a family history of cancer and the most common TNM stage was T1 (48%). The most common risk assessments (following the NCCN guidelines) were low- or intermediate-risk (both 35% of pts), followed by high risk (26%) and highest risk (4%). Urologists rated tumor stage and grade as the two most important factors for evaluating pt risk level. For pre-treated pts, the most common prior therapy was TURBT (87.1%). Among newly diagnosed pts and pts with recurrent NMIBC, 24% and 32% received BCG, respectively (overall 27%). BCG was most commonly monotherapy and at a dose of 120mg in both newly diagnosed (98% monotherapy/72% 120mg) and recurrent (96% monotherapy/74% 120mg) settings. Most urologists gave a schedule of induction (85%; BCG weekly, duration 6–8 weeks) followed by intensive Tx (65–69%; BCG Q2W, 6–8 weeks), and then maintenance (54%-68%;monthly; ≤1 year), depending on risk level. Compared with chemotherapy, 88% of responders agreed that BCG was more effective in preventing recurrence. The most important factors for choosing BCG were recurrence frequency and risk level and TNM stage (Table); 89% and 88% of urologists responded that limited BCG supply and pricing were important factors in continuing BCG. Post BCG, the most popular subsequent Tx was radical/partial cystectomy (35%) and intravesical chemotherapy (22%) although 15% of responders indicated they would extend BCG. Conclusions: These descriptive survey data provide important insights into real-world BCG utilization and factors influencing BCG use in NMIBC in China. [Table: see text]
Chemoradiation versus cystectomy for locally advanced bladder cancer: A global, propensity-matched retrospective cohort study.
Authors: Mackey James David , Atieh Khaled
Published: June 2024

e16603

Background: Prior studies have attempted to determine whether chemoradiation is comparable to cystectomy for treatment of locally advanced bladder cancer. Some studies have shown no significant difference, while others indicate a small benefit in favor of cystectomy. The purpose of this study was to use the large, multi-institutional TriNetX database to evaluate for differences in overall survival and development of metastatic disease between the two treatments at five years. Methods: The TriNetX research database was used for this study. Two patient cohorts were created by utilizing International Classification of Disease-10 (ICD-10) codes and Current Procedural Terminology (CPT) codes. Both cohorts of patients were required to have a diagnosis of bladder cancer (C67) and were prohibited from having any known sites of metastatic disease (C78 or C79). The cystectomy cohort was constructed by using CPT codes 51590, 51595, or 51596. Chemoradiation treatment was identified by encounters for chemotherapy and radiation occurring on the same day (Z51.11 and Z51.0). The chemoradiation cohort was prohibited from having any cystectomy surgery, and the cystectomy cohort was prohibited from having had any radiation treatment. The cohorts were then balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, and ethnicity. This resulted in 232 patients in each arm. The cohorts were then compared for the outcome of death at 5 years, as well as the development of metastases to lymph nodes, lung, bone, liver, and peritoneum (C79.51, C78.0, C77, C78.7, C79.89). Results: Patients who underwent chemoradiation had significantly higher mortality at five years than those that underwent cystectomy (38.4% vs 20.3%, RR 1.89, 95% CI (1.40,2.56), P value < 0.0001). Patients treated with chemoradiation were also six times more likely to develop metastatic disease to lymph nodes, lung, bone, liver, or peritoneum (31.0% vs 5.2%, RR 6, 95% CI (3.3,10.8), P value < 0.0001). Conclusions: Patients with stage II or III bladder cancer can be treated with either cystectomy or chemoradiotherapy. Both options are Category 1 recommendations of the National Comprehensive Cancer Network, with patient preference often a deciding factor. This study found that the development of metastatic disease and mortality may be more substantial than previously believed, suggesting that bladder cancer is a relatively chemoradiation resistant malignancy.
Burden of non-muscle–invasive bladder cancer (NMIBC) leveraging a novel American Urological Association Quality Registry Qdata module: A real-world data analysis based on manual data abstraction.
Authors: Gallagher Shannon , Abdul Sultan Alyshah , Sands Kathryn , Chin Iris , Cote Sarah , Spigelman Samuel , Baculea Simona , Bepple Jennifer
Published: June 2024

e16607

Background: Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). However, there is limited evidence on the real-world burden of NMIBC by risk categories specified by the International Bladder Cancer Group (IBCG). Large routinely collected data lack reliable granular information on tumor size, multiplicity, grade, and recurrence history and can lead to misclassification. Methods: Electronic health record data from the American Urological Association (AUA) Quality (AQUA) Registry, which is a national Qualified Clinical Data Registry was leveraged within the de-identified NMIBC Qdata module to identify and risk stratify patients based on the updated IBCG guidance. This EHR-derived module was linked to Komodo Health claims to increase capture of procedures. A random sample (n=2,500) from approximately 54,000 study-eligible NMIBC patients within the overall database was identified between 2015 and 2022 with a valid T-stage reading anytime in their medical record. Information on relevant parameters (e.g., tumor size, multifocality, stage, grade) were manually abstracted based on a standard protocol and summarized. Abstraction quality was ensured through a comprehensive disease and study training and test cases in which the clinical abstractor met ³85% agreement with the gold standard. Audits were also performed on ³10% of cases. Results: Of the 501 records initially abstracted, 96% of patients had information on relevant parameters to classify them by risk based on the IBCG guidelines. At first presentation during the study period, the majority of patients were Ta (65%), whereas 8% and 27% presented as Tis and T1, respectively. During the observation period, 291 (65%) patients were classified as high-risk whereas 114 (24%) and 135 (28%) were ever classified as low and intermediate risk, respectively. For patients with intermediate risk NMIBC, the proportion of newly diagnosed versus recurrence was similar (50%). Conclusions: This study leveraged one of the largest US-created NMIBC databases to provide contemporary, real-world distribution of NMIBC risk founded on the updated IBCG guidance. The study demonstrates that a high proportion of NMIBC patients that have explicit tumor characteristics documented are classified as high risk followed by intermediate risk, warranting the need for innovative therapies in these patient groups.
Stratified absolute benefit with adjuvant immunotherapy (aIO) in muscle-invasive bladder cancer (MIBC): A meta-analysis.
Authors: Naqvi Syed Arsalan Ahmed , Saxena Akshat , Faisal Kunwer Sufyan , Bibi Arifa , Khan Muhammad Ali , Cobran Ewan Kemar , Hussain Syed A. , Riaz Irbaz Bin , Bryce Alan Haruo , Singh Parminder
Published: June 2024

e16619

Background: Should patients (pts) with MIBC receive aIO given the DFS benefit seen in AMBASSADOR and CheckMate 274 trials is an important clinical question. Thus, we aimed to quantify the magnitude of absolute benefit across different subgroups to aid clinicians in shared decision-making with their patients. Methods: Phase III trials evaluating aIO as compared to observation or placebo (obs/plac) in pts with MIBC were considered eligible. Outcomes of interest included DFS and OS. Pre-specified subgroups included disease location, PDL1 status, neoadjuvant chemotherapy (NAC) receipt, and tumor and nodal (TN) staging. Pairwise comparisons were made using a DerSimonian-Lairds (DL) random-effects meta-analysis. Stratified baseline risks (obtained from clinical trials) and relative effect estimates were used to estimate corresponding intervention risks (CIRs). The difference in CIRs and baseline risk was calculated to present absolute risk differences (ARDs) in each subgroup category. Results: Analysis included three trials with 2220 pts (pembrolizumab, nivolumab, and atezolizumab assessed in each). No significant difference was observed in OS with aIO compared to obs/plac (hazard ratio: 0.91; 0.76-1.09). However, aIO significantly improved DFS compared to obs/plac (0.76; 0.64-0.91) in the overall population. In pts with bladder/lower tract disease, aIO improved DFS compared to obs/plac (0.72; 0.56-0.92); however, no significant difference was observed in DFS in pts with upper tract disease. There was a statistically significant effect modification by disease location (p: 0.01). Adjuvant IO significantly improved DFS in PDL1- (0.78; 0.64-0.94) but not in PDL1+ pts (0.75; 0.52-1.08). Likewise, aIO significantly improved DFS in pts who received NAC (0.69; 0.53-0.90) but not in pts who did not receive NAC (0.89; 0.75-1.05). In terms of TN staging, aIO improved DFS in T2-3N0 (0.73; 0.57-0.94), T4N0 (0.76; 0.61-0.95), and in T2-4N1 patients (0.75; 0.59-0.95). No statistically significant modifications were observed among these subgroups. Stratified ARDs for DFS by each subgroup are outlined (Table). Conclusions: When delayed disease progression is a vital consideration, a risk-adapted strategy for the optimal patient selection to receive aIO should be considered. Disease location (lower tract/bladder), node positivity, and receipt of NAC emerged as groups likely to derive greater benefit with aIO. [Table: see text]
Real-world (rw) treatment (tx) patterns, sequencing, and outcomes in US patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) treated with avelumab first-line maintenance (1LM).
Authors: Carson Kenneth Robert , Ike Chiemeka , Mahmoudpour Seyed Hamidreza , Monzon Sebastian , Fragkogianni Stamatina , Kearney Mairead
Published: June 2024

e16621

Background: In June 2020, avelumab 1LM was approved in the US for pts with la/mUC without progressive disease (PD) after 1L platinum-based chemotherapy (PBC). This rw study describes pt characteristics, tx patterns, and outcomes in pts who received avelumab 1LM. We report exploratory analyses by baseline metastatic site. Methods: A retrospective cohort of pts diagnosed with la/mUC (T4b, N2/3, and/or M1) who received systemic tx after approval of avelumab 1LM was identified from deidentified records in the Tempus database. Pts with no evidence of PD after completing 1L PBC were considered eligible for 1LM. 1LM was differentiated from second-line (2L) tx based on recorded clinical intent or algorithmically based on immuno-oncology tx initiated within 180 days of 1L PBC completion without recorded PD. Rw overall survival (OS), progression-free survival (PFS), and time to next tx (TTNT) were estimated using Kaplan-Meier methods. Results: By data cutoff (Nov 2023), 1485 pts had received 1L tx after approval of avelumab 1LM. Median age at diagnosis was 70 y, 74% were men, 62% were White, 88% had transitional cell carcinoma, and 62% had metastatic/stage IV disease. 1L tx was PBC in 63% (942/1485), which included cisplatin in 62% (581/942), carboplatin in 34% (326/942), and oxaliplatin in 4% (35/942), alone or in combination. 87% (820/942) were eligible for 1LM after completing 1L PBC, of whom 38% (313/820) had recorded 1LM tx, which was avelumab in 58% (180/313). Median follow-up from 1LM start was 13.5 months. Median (95% CI) rwOS and rwPFS from avelumab 1LM start was 20.6 (17.6-25.3) and 6.2 (4.6-13.7) months, respectively. Analysis by metastatic site is shown in the table. After avelumab 1LM, 37% (67/180) received 2L tx, most commonly with enfortumab vedotin (EV; 64% [43/67]); median rwOS from start of 2L EV was 13.5 months (95% CI, 11.6-NE). Conclusions: Despite limited follow-up, this study demonstrates the rw effectiveness of avelumab 1LM in pts whose disease has not progressed on 1L PBC. Results corroborate JAVELIN Bladder 100 data and recent rw studies from multiple countries. Our study also provides early evidence of the use and effectiveness of 2L EV after the JAVELIN Bladder regimen of 1L PBC without PD followed by avelumab 1LM. Understanding OS outcomes in pts with specific metastatic patterns is important for improving individualized care. Future studies with longer follow-up are warranted to evaluate rw benefits of the avelumab 1LM in selected pt groups. [Table: see text]
Genetic analysis of metastatic castration resistant prostate cancer patients treated with Lu-177 PSMA radioligand therapy.
Authors: Yilmaz Burcak , Chalker Cameron , Yu Yun , Kaempf Andy , Mittra Erik , Mallak Nadine , Sokolova Alexandra
Published: June 2024

e17063

Background: We aim to elucidate associations between mutations, treatment response, and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients undergoing Lu-177 PSMA radioligand therapy (PSMA-RLT). Methods: We reviewed mCRPC patients who received at least 1 cycle of PSMA-RLT between May 2022 and October 2023, assessing mutations that included ATM, ATR, BRCA1/2, BRIP1, CHEK2, EPCAM, FANCA, GEN1, HOXB13, MLH1, MSH2/6, NBN, PALB2, PMS2, RAD51C, RAD51D, and TP53. Clinical variables were collected. Biochemical response (BR) was defined as PSA reduction ≥ 50% over the complete course of PSMA-RLT. PSMA PET segmentation was performed with MIM PUR PSMA (version 7.2.9). OS was measured from start of PSMA-RLT, estimated by the Kaplan-Meier method, and modeled with Cox regression; BR was modeled with logistic regression. Results:71 mCRPC patients with median age of 72 (range: 48-90) were included. 47 (66%) patients completed ≥ 4 PSMA-RLT cycles with 30% receiving all 6 cycles. 35 (49%) had a GS ≥ 8 (11 unknown) and 33 (46%) had metastases at diagnosis. 25 patients had somatic testing, 29 had germline testing, 16 had both, and 1 was unknown. All tumors were microsatellite stable. 6 had a BRCA 1/2 mutation, of which 3 were in the germline; 9 carried a non- BRCA homologous recombination deficiency (HRD) mutation. 17 had a mutation in p53, RB1, or PTEN. There was no correlation between mutation status and any pretreatment PET parameters, BR, or OS. BR was achieved in 48%. At median follow-up of one year, 41% of patients died; median OS was 12 months (95%CI: 10 – NA). No significant correlation was found when comparing prior therapy, mutation status, and any pretreatment PET parameter with BR or OS. Patients receiving all 6 cycles were 7 times more likely to achieve BR (p = 0.002). Conclusions: There was no significant association between PSMA-RLT outcomes and either mutation status or pretreatment PET parameters. This study is limited by the low number of patients with genomic alterations. [Table: see text]
Real-world treatment patterns with lutetium-177-PSMA-617 (177-Lu-PSMA) in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Dwabe Sami , Yazdanpanah Omid , Warnecke Brian , Benjamin David Joseph , Rezazadeh Arash , Mar Nataliya
Published: June 2024

e17064

Background: The VISION study demonstrated improved outcomes with up to 6 doses of177-Lu-PSMA plus standard-of-care (SOC) therapy versus SOC alone in pre-treated mCRPC patients, which led to its regulatory approval on 03/23/22. This is our real-world experience with 177-Lu-PSMA at the University of California, Irvine and Hoag Hospital. Methods: This is a retrospective analysis of 22 patients with mCRPC treated with 177-Lu-PSMA at the University of California, Irvine and Hoag Hospital since 03/23/2022. Baseline demographic, pathologic, and genomic characteristics of all patients who received 177-Lu-PSMA (along with their outcomes) were analyzed. Results: Selected baseline characteristics of the study population are included in the table, which contrast treatment responders and non-responders. At the time of this analysis, 22.7% (5/22) of patients completed all 6 planned cycles of 177-Lu-PSMA, 40.9% (9/22) discontinued early due to disease progression, 18.2% (4/22) are still receiving therapy, 9.1% (2/22) stopped treatment due to toxicity, and 9.1% (2/22) discontinued for other reasons. PSA reduction by at least 50% (PSA50) was achieved in 59.1% (13/22) of patients, 27.3% (6/22) achieved < PSA50, and 3/22 (13.6%) had no PSA response at all. In PSA responders, the median time to PSA nadir was 11.7 weeks [range: 2.3 - 38.0], while the median time to second PSA rise above nadir was 6.0 weeks [range, 4.0 – 22.3]. Treatment related toxicities occurred in 54.5% (12/22) of patients, including 22.7% with dry mouth, 22.7% with fatigue, and 13.6% with nausea. Conclusions: This dataset highlightsreal-world treatment patterns with 177-Lu-PSMA, which is an active and well-tolerated therapy. Despite initial response, some patients appear to have quick PSA progression, which led to early treatment discontinuation. We set out to evaluate if there were any baseline characteristics predictive of response among our patients. Ultimately, our data did not show any factors predictive of response to therapy. Given its financial toxicity, further studies identifying which patients are most likely to respond to 177-Lu-PSMA are indicated. [Table: see text]
Interim analysis of clinical data and reasons for initiating relugolix on a cohort of US patients: The OPTYX study.
Authors: Spratt Daniel Eidelberg , McKay Rana R. , Ross Ashley , Lowentritt Benjamin H , Flanders Scott C , Zhu Yajun Emily , Nolley Susana , Hong Agnes , Gatoulis Sergio C , Dorff Tanya B.
Published: June 2024

e17072

Background: Relugolix is an oral GnRH receptor antagonist indicated for advanced prostate cancer treatment. The OPTYX study is prospectively collecting clinical and patient outcomes data from US patients initiating relugolix in routine care settings to evaluate the long-term outcomes of relugolix therapy. An interim analysis of key baseline variables, reasons for starting relugolix therapy and treatment patterns is presented. Methods: The multi-center observational OPTYX study aims to enroll 1,000 patients with prostate cancer starting relugolix therapy. The current study population includes diverse disease states, treatment circumstances (eg, monotherapy, combination therapy, or intermittent therapy) and clinical settings representative of real-world patterns of care. Baseline demographics, clinical characteristics, reasons for initiating treatment, and treatment patterns from Oct 2022 to Oct 2023 are described. Results: As of October 2023, 394 men were enrolled in the OPTYX study and received relugolix with a median treatment duration of 114 days. The median age was 71 years; 78.7% of patients self-reported as White, 14.2% as Black. Enrollment occurred through Urology, Oncology and Radiation Oncology practices. Most patients (61.2%) had baseline PSA <20 ng/ml. Mean (SD) baseline testosterone was 317.7 (238.5) ng/dL. At baseline, 15.2% of patients had received prior radiotherapy and 20.0% had prior androgen deprivation therapy. Known distant metastases were found in 24.6% of patients. A total of 135 patients (34.3%) received relugolix in combination with other therapies (Table). Top 3 reasons physicians prescribed relugolix were oral instead of injection (40.6%), rapid testosterone suppression (37.6%) and safety (25.1%), while patient reasons were physician recommendation (74.6%), oral instead of injection (35.5%) and safety (8.9%). In 10.7% of patients who discontinued therapy for any reason, 3.3% completed the planned regimen while 3.6% discontinued due to adverse events. No new serious safety signals have been identified. Conclusions: The OPYTX study is evaluating real-world experience with relugolix, including diverse disease states, practice settings and physician specialties. More than a third of patients and physicians favored oral versus injectable formulation, and more than a third used relugolix in combination with other therapies. There was low unplanned discontinuation of relugolix at data cut-off. Clinical trial information: NCT05467176 . [Table: see text]
Association of very deep prostate-specific antigen (PSA) decline with longer radiologic-progression-free survival (rPFS) in patients with metastatic castration-sensitive prostate cancer.
Authors: Kapar Caner , Tuğcu Volkan , Şahin Selçuk , Güler Haydar , Kilickap Saadettin , Tural Deniz
Published: June 2024

e17074

Background: Previous studies have shown rare PSA and rapid reduction in PSA to be associated with survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with ADT, docetaxel, abiraterone, or enzalutamide. The ability to accurately rate nadir PSA level may help inform treatment intensification or de-escalation decisions. PSA nadir level was determined as 0.2 ng/mL for mCSPC in previously reported. However, the deeper the reduction in PSA level, the better the survival outcomes in prostate cancer may be. In the current study, we evaluated the association between a very deep PSA decline and rPFS in patients treated with mCSPC. Methods: Patients with mCSPC treated with ADT, Abiraterone acetate, Enzalutamide, or Docetaxel in the first line setting were included in the study. Serum PSA values were recorded at baseline, 1st, 3rd, and 6th months (mo ). Based on the lowest reached PSA level, patients were divided into four subgroups (PSA <=0.02 ng/mL, PSA 0.02–0.2ng/mL, PSA 0.2-4ng/mL, PSA >4 ng/mL). Median follow-up and rPFS were estimated using the Kaplan-Meier method. Results: Data from 151 patients were analyzed. 11 patients were excluded due to insufficient data, and 7 patients were not included due to inadequate follow-up. The median age was 68 (38–91) years, and the majority of patients (51.1%) had Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 1≥. Of the patients, 54.1% had high-volume disease, and 65.4% had synchronous metastasis. Additionally, 82% of the patients had bone metastasis, 15% had lung metastasis, and 7% had liver metastasis. When patients were stratified into 4 subgroups based on their lowest PSA levels, the distribution was as follows: PSA<=0.02 ng/mL, 15% (n=20); PSA 0.02–0.2 ng/mL, 20.3% (n=27); PSA 0.2–4 ng/mL, 48.9% (n=65); PSA >4 ng/mL, 15.8% (n=21). The median follow-up time was 32.3 (3–86) mo. The median rPFS for all populations was calculated as 18.1 mo [15.1–20.9 mo, 95% CI]. In the PSA<=0.02 ng/mL group, the median rPFS was 49.8 mo [38–61.6 mo, 95% CI]; PSA 0.02–0.2 ng/mL group, 27 mo [16.8–37.2 mo, 95% CI]; PSA 0.2–4 ng/mL group, 16 mo [13.5–18.8 mo, 95% CI]; PSA >4 ng/mL group, 8 mo [1.4-14.6 mo, 95% CI]. The statistical analysis revealed a significant relationship between very deep PSA levels and rPFS [p<0.01]. 5-year rPFS were %78, %16, %8 and %0 for each group, respectively(p<0.01). Conclusions: Very deep prostate-specific antigen decline is associated with longer rPFS in patients with mCSPC. Very deep prostate-specific antigen decline is a more potent surrogate marker for longer rPFS and it can be used new primary endpoint for clinical trials.
Sequential ADT and abiraterone acetate plus prednisone versus combined ADT with abiraterone acetate plus prednisone for metastatic castration-sensitive prostate cancer: A propensity score-matched study.
Authors: Yang Zhenyu , Zhao Diwei , Wang Jun , Long Xingbo , Chen Dong , Zhou Fangjian , Li Yonghong
Published: June 2024

e17075

Background: Previous studies showed that combination of androgen deprivation therapy (ADT) with abiraterone acetate plus prednisone was associated with longer survival than ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). The aim of this retrospective propensity score-matched study was to compare the effects of sequential treatment of ADT and abiraterone acetate plus prednisone (sequential treatment cohort), and combination treatment of ADT with abiraterone acetate plus prednisone (combination treatment cohort), in men with newly diagnosed mCSPC. Methods: The sequential treatment cohort received ADT or ADT plus first-generation nonsteroidal antiandrogen (NSAA) as first-line therapy, then ADT and abiraterone acetate plus prednisone after progression. The combination treatment cohort received ADT and abiraterone acetate plus prednisone as first-line therapy. Patients with newly diagnosed mCSPC treated with ADT, ADT plus first-generation NSAA, or ADT plus abiraterone acetate in our center between June 2014 and July 2022, were respectively identified. Patients treated with sequential treatment or combination treatment were evaluated through propensity score matching (PSM) based on baseline clinical characteristics. The primary outcome was abiraterone failure-free survival (aFFS). Secondary outcomes including overall survival (OS), PSA response. Results: Clinical characteristics were balanced after PSM and 117 patients were included in each cohort. The aFFS was 30.7 and 30.6 months in sequential and combination treatment cohort, respectively, no statistically significant difference was observed (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.64 -1.27; p = 0.526). Similarly, there was no statistically significant difference in overall survival (OS, HR 0.92, 95% CI 0.57 -1.49; p = 0.388) between sequential and combination treatment. Conclusions: Patientswith newly diagnosed mCSPC treated with sequential ADT and abiraterone acetate plus prednisone, had similar aFFS and OS, compared to men treated with combined ADT and abiraterone acetate plus prednisone, according to our preliminary results. Our data indicate that sequential treatment of ADT and abiraterone acetate might be considered as an alternative to newly diagnosed mCSPC.
Clinical characteristics and outcomes of veterans with metastatic hormone-sensitive prostate cancer (mHSPC) based on volume of disease and site of metastases.
Authors: Stackable Kaitlin , Pickett Carley , Riekhof Forest , Fedele Nicholas , Baxi Priya , Ingram Kara , Karunanandaa Krishny , Govindan Srinivas , Cheranda Nina , Agarwal Rohan , Schoen Martin W.
Published: June 2024

e17083

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is categorized by volume of disease and high tumor volume is associated with worse outcomes. Assessment of volume of disease and site of metastases at diagnosis may help risk stratify patients with mHSPC. This study describes patient characteristics and survival in U.S. veterans treated for mHSPC. Methods: Veterans were identified with initial diagnosis of SEER stage ‘distant’ prostate cancer. All veterans had androgen deprivation therapy (ADT) initiated within 4 months of diagnosis and followed until September 2023. Veterans treated with ADT alone during 2018, ADT+docetaxel (DOC) from 7/2016-6/2021 or androgen receptor pathway inhibitors (ARPIs) abiraterone, enzalutamide, apalutamide, and darolutamide from 7/2017-6/2021 were included if initiated within 4 months after ADT. Veterans were categorized as high or low volume of disease by chart review. If patients had more than one site of metastasis, they were categorized as follows: any liver, any lung, any high volume bone. Age, PSA, and body mass index (BMI) were collected at diagnosis and compared by ANOVA or Kruskal-Wallis with Bonferroni correction for multiple comparisons. Results: 1520 veterans were identified with 886 high volume bone metastases, 154 lung metastases, 70 liver metastases, and 410 low volume patients. Mean age of patients was 72.3 years (SD 0.4) with median PSA of 103.2 ng/mL and mean BMI of 27.4. There was no difference in mean age between high volume and low volume (72.3 vs. 72.5 years, p=0.28), however median PSA was higher in high volume (152.0 vs. 48.8 ng/mL, p<0.001) and median BMI was lower in high volume (26.5 vs. 27.5, p=0.002). High volume metastasis was associated with shorter survival (31.2 vs. 56.3 months, p<0.001). For site of metastases, there was no difference in age between location (p=0.365), PSA was higher in liver, lung, and high volume bone compared to low volume while for BMI, only liver metastasis was associated with significantly lower BMI. Liver metastasis was associated with shorter survival compared to low volume, high volume bone, and lung metastasis (all p<0.001 by log-rank). Conclusions: High volume disease and liver metastases were associated with shorter survival in veterans with mHSPC. Presence of liver metastasis was independently associated with decreased overall survival compared to high volume bone or lung metastases. Volume of disease and location of metastases may provide information for prognostication in mHSPC. [Table: see text]
Descriptive analysis of patients on active surveillance escalating to treatment for localized prostate cancer.
Authors: Son Young , Wu Edward , Akanda Shawon , Klimowich Katelyn , Mueller Thomas , Brown Gordon Andrew
Published: June 2024

e17092

Background: It is predicted that 1 in 8 men will be diagnosed with prostate cancer and 1 in 41 men will die of prostate cancer, making it the second leading cause of death in men. However, not all diagnosis of prostate cancer is clinically significant and active surveillance (AS) can be an option. Although AS is an option, an estimated 50% of patients will progress to treatment within 5-10 years. In this study, we aim to characterize those patients that required escalation to treatment from AS. Methods: A multicenter retrospective review was performed of patients that were had biopsy proven prostate cancer that elected to undergo AS. The cohort was subdivided into those that progressed to treatment (radiation, surgery, or hormonal therapy) and those that continued AS. Patient demographics, prostate biopsy characteristics, and biomarker usage was analyzed between the two groups. Descriptive analysis was performed and a multivariate logistic regression was performed. Results: A total of 158 patients were reviewed from 2021-2023. Among the cohort, 55 (34.2%) progressed to treatment while 106 (65.8%) remained on AS. The treated cohort were younger (63.2 vs. 68.6), had lower initial PSA (1.6 vs. 4.7), lower % free PSA (10.5 vs. 20.6), and higher number of cores positive (3.9 vs. 2.7) on biopsy. There was no difference in biomarker testing including Prolaris, Decipher, and Oncotype Dx between the treated and AS group. On adjusted analysis, age (OR 0.9, 0.81 – 0.99, P=0.035) and initial PSA (OR 0.38, 0.22 – 0.59, P<0.001) were predictive covariates into treatment (Table). Conclusions: AS is an option for favorable prostate cancer. We show that there was no difference in Biomarkers, PIRADS, and PSAD between the treated and the AS group. Escalation to treatment from AS should be a shared decision making between provider and patient. Our multicenter, real-world analysis shows that younger patients and lower initial PSA were factors that were associated with escalation to treatment. [Table: see text]
Prognostic impact of BRCA mutation on metastasis-free survival in a localized/locoregional high-risk real-world prostate cancer population.
Authors: Brito Frances , Song Rebecca , Rajan Aditya , Shami Jessica , Barnicle Alan , Zhao Jimmy , Dow Jessica , Khosla Sajan , Roy David , Dempster Sara
Published: June 2024

e17104

Background: Understanding the prognostic impact of BRCA mutation status across prostate cancer (PCa) patient segments is critical to deploying the right therapies at the right time in a patient’s journey. Prior studies have shown that germline BRCA mutations are associated with poorer outcomes in an all-risk localized PCa population. To examine whether this association extends to a high-risk PCa population with either somatic or germline BRCA mutations, we evaluate the prevalence and independent prognostic impact of BRCA mutations in a real-world (RW), high-risk, localized/locoregional PCa population. Methods: A retrospective study (2016-2023) was performed using a de-identified multimodal RW dataset of patients undergoing Tempus xT next-generation sequencing. Eligible patients had localized/locoregional PCa at primary diagnosis (pDx), were biopsied prior to metastatic diagnosis, received adjuvant radiotherapy and/or had a prostatectomy, and had an evaluable Gleason score (GS). Risk groups were categorized as low/intermediate (low/int)-risk (total GS <8) and high-risk (total GS ≥8). BRCA status was defined as BRCAm if the patient had a short variant that was predicted or known to be pathogenic or a copy number loss in BRCA1 or BRCA2 and BRCAwt if no mutation was detected. Median real-world metastasis-free survival (rwMFS), defined as time from primary intervention to first metastatic diagnosis, was estimated using Kaplan-Meier methods and stratified by combined BRCA status and risk group (BRCAm high-risk, BRCAm low/int-risk, BRCAwt high-risk, BRCAwt low/int-risk). To assess the independent prognostic value of BRCA status among all patients and within a high-risk subset, two multivariate Cox models were performed adjusting for risk group, age at pDx, baseline PSA, primary intervention type, and T and N stage at pDx. Results: Among 607 eligible patients, 67 (11%) had a BRCA mutation (11 germline, 27 somatic, 29 tumor/unknown). Median rwMFS was longest in the BRCAwt low/int-risk group (n=147) at 50 mos (95% CI: 41, NA), followed by the BRCAwt high-risk group (n=393) at 36 mos (95% CI: 31, 42), and the BRCAm high-risk group (n=61) at 22 mos (95% CI: 11, 45). Median rwMFS estimates in the BRCAm low/int-risk group were unreliable due to a small sample size (n=6). From the adjusted Cox model, BRCAm patients had higher risk of metastasis compared to BRCAwt patients in the all-risk group (HR=1.48, 95% CI: 1.06, 2.09) and in the high-risk subset (HR=1.50, 95% CI: 1.04, 2.17). Conclusions: Our findings show that BRCAm is independently prognostic of metastasis in a RW, localized/locoregional, high-risk PCa population. We identify high-risk BRCAm patients as a subgroup with significantly elevated risk of developing metastasis; clinical trials with targeted therapeutic intervention may be needed to address the clinical unmet need.
Efficacy and safety of envafolimab plus lenvatinib combined with etoposide in recurrent ovarian, peritoneal, and fallopian tube cancer: An open-label, single-arm study—The ENLEN-OC-001 study.
Authors: Yu Tianxiang , Ding Bo , Xu Jingyun , Liu Sicong , Shen Yang
Published: June 2024

e17570

Background: Previous studies have shown that combination therapy of immune checkpoint inhibitors (ICIs) may demonstrate more satisfactory efficacy in patients with ovarian cancer compared to monotherapy. Envafolimab is the first globally approved subcutaneously administered PD-L1 monoclonal antibody, which means there is less hospitalization is required, providing the possibility of live-in care. We aim to assess the efficacy and safety of the combination therapy of envafolimab plus lenvatinib combined with etoposide in patients with platinum-resistant recurrent ovarian cancer. Methods: In this single-arm, open-label study, we recruit patients with platinum-resistant ovarian cancer at the Zhongda Hospital, Southeast University (China). The specific regimen consists of subcutaneous envafolimab at a dose of 400mg, oral lenvatinib (12mg per day for patients weighing ≥60kg; 8mg per day for patients weighing <60kg) once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide is administered for six to ten cycles. The treatment will continue until disease progression or adverse event. The primary endpoint is objective response rate (ORR) assessed by investigators according to RECIST 1.1 criteria. Disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety are evaluated as secondary endpoints . Data are summarized by descriptive statistics; time-to event endpoints are analyzed using Kaplan-Meier method. Results: From Jun 18, 2022, to Oct 31, 2023, we screened 16 and enrolled 12 patients. At the data cutoff date (Nov 30, 2023), 5 (41.7%) patients had discontinued the study, and 7 (58.3%) patients remained on treatment. Median follow-up was 8.6 months (IQR: 3.3-17.7). Based on the data collected, Objective responses were achieved in 4 (36.3%; 95% CI 10.9–69.2) of 11 patients who had at least one post-baseline efficacy assessment. DCR was 81.8%( 95% CI 48.2–97.7) and median duration of response was 7.4 months (95% CI 4.2–NA). Median progression-free survival was 9 months (95% CI 5.5–NA) and median OS was not reached. The most common grade 3 or 4 adverse events were leukopenia (2 [16.7%]) and thrombocytopenia (2 [16.7%]). No serious adverse events and treatment-related deaths were recorded. Conclusions: The combination of envafolimab plus lenvatinib combined with etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant ovarian cancer. Clinical trial information: NCT05422183 .