Riaz, Irbaz Bin

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

AbstractIntroductionStructured data capture requires defined languages such as minimal Common Oncology Data Elements (mCODE). This pilot assessed the feasibility of capturing 5 mCODE categories (stage, disease status, performance status (PS), intent of therapy and intent to change therapy).MethodsA tool (SmartPhrase) using existing and custom structured data elements was Built to capture 4 data categories (disease status, PS, intent of therapy and intent to change therapy) typically documented as free‐text within notes. Existing functionality for stage was supported by the Build. Participant survey data, presence of data (per encounter), and time in chart were collected prior to go‐live and repeat timepoints. The anticipated outcome was capture of >50% sustained over time without undue burden.ResultsPre‐intervention (5‐weeks before go‐live), participants had 1390 encounters (1207 patients). The median percent capture across all participants was 32% for stage; no structured data was available for other categories pre‐intervention. During a 6‐month pilot with 14 participants across three sites, 4995 encounters (3071 patients) occurred. The median percent capture across all participants and all post‐intervention months increased to 64% for stage and 81%–82% for the other data categories post‐intervention. No increase in participant time in chart was noted. Participants reported that data were meaningful to capture.ConclusionsStructured data can be captured (1) in real‐time, (2) sustained over time without (3) undue provider burden using note‐based tools. Our system is expanding the pilot, with integration of these data into clinical decision support, practice dashboards and potential for clinical trial matching.

Purpose of review Low-volume prostate cancer is an established prognostic category of metastatic hormone-sensitive prostate cancer. However, the term is often loosely used to reflect the low burden of disease across different prostate cancer states. This review explores the definitions of low-volume prostate cancer, biology, and current evidence for treatment. We also explore future directions, including the impact of advanced imaging modalities, particularly prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans, on refining patient subgroups and treatment strategies for patients with low-volume prostate cancer. Recent findings Recent investigations have attempted to redefine low-volume disease, incorporating factors beyond metastatic burden. Advanced imaging, especially PSMA PET, offers enhanced accuracy in detecting metastases, potentially challenging the conventional definition of low volume. The prognosis and treatment of low-volume prostate cancer may vary by the timing of metastatic presentation. Biomarker-directed consolidative therapy, metastases-directed therapy, and de-escalation of systemic therapies will be increasingly important, especially in patients with metachronous low-volume disease. Summary In the absence of validated biomarkers, the management of low-volume prostate cancer as defined by CHAARTED criteria may be guided by the timing of metastatic presentation. For metachronous low-volume disease, we recommend novel hormonal therapy (NHT) doublets with or without consolidative metastasis-directed therapy (MDT), and for synchronous low-volume disease, NHT doublets with or without consolidative MDT and prostate-directed radiation. Docetaxel triplets may be a reasonable alternative in some patients with synchronous presentation. There is no clear role of docetaxel doublets in patients with low-volume disease. In the future, a small subset of low-volume diseases with oligometastases selected by genomics and advanced imaging like PSMA PET may achieve long-term remission with MDT with no systemic therapy.

98 Background: The risk of secondary primary malignancies (SPM) among the survivors of GU cancer is not well-established. In this study, we attempt to describe the patterns of SPMs in patients diagnosed with GU cancers. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (SEER*Stat 8.4.2) was searched to obtain data on the incidence of SPM in adult patients (age >18 years) diagnosed with GU cancers, including prostate, renal, and bladder cancer. Standardized incidence ratios (SIRs) with a 95% confidence interval (CI) were calculated. SIR was defined as the observed SPMS from each category divided by the expected number of SPMs in the age-matched US population for the same period. The data was further stratified by age (<50y, 50-70y, >70y), race (White, Black, Asian/Pacific Islander), ethnicity (Hispanic, non-Hispanic), chemotherapy, and radiotherapy exposure. Results: A total of 1,041,217 patients were included in this analysis. In patients diagnosed with GU cancer, the incidence of overall SPM was 11%. Particularly, patients with GU cancers were observed to have a high incidence of Endocrine system SPM (1.52; 1.45-1.59), and urinary system SPM (1.51; 1.49-1.53) These results were consistent by different sociodemographic groups. In patients diagnosed with prostate cancer, the incidence of thyroid SPM was increased (1.31; 1.23-1.39). Particularly, prostate cancer patients treated with radiation therapy had increased incidence rates of SPM in the peritoneum, omentum and mesentery (1.57; 0.79-2.81) and urinary bladder (1.36;1.32-1.40) was higher as compared to those with no exposure to radiation therapy (1.11;1.08-1.13 and 1.03;1-1.06 respectively). Bladder cancer patients had an overall increased incidence of SPM in the esophagus (1.21; 1.08-1.35), lung, bronchus, trachea, and other respiratory organs (1.97;1.92-2.01), prostate (3.50;3.4-3.6) and kidney (1.86;1.76-1.97). A higher incidence of renal pelvis, ureter and other urinary organ SPM (11.08;10.48-11.07) was also notable in this population. Similarly, kidney cancer patients had a higher incidence of the endocrine system (3.00;2.74-3.27), prostate (1.24;1.2-1.29) and bladder 1.78;1.68-1.79 SPMs. Conclusions: This population-based study shows an increased risk of SPM development in GU cancer survivors compared to the general population. Clinicians should keep a high index of suspicion for SPMs and initiate appropriate workups at early warning signs.

93 Background: The treatment paradigm for mCSPC patients has rapidly evolved over the last few years with the emergence of triplet therapy and prognostication by volume of disease. However, the health economic implications of triplet therapy by disease volume remain unclear. Methods: A Markov model where patients transitioned between the progression-free, progression and death states was developed. State utilities were derived from the LATITUDE trial. Point probabilities for overall survival, progression-free survival, grade ≥ 3 and 5 toxicities were obtained from the eligible mCSPC phase III clinical trials. Medicare Advantage and commercial total paid amounts (2022 US$) of treatments were obtained from OptumLabs Data Warehouse. Costs and disutilities of adverse events were derived from published literature. Half-cycle corrected costs and utilities were accrued monthly over a 20-year lifetime horizon and were discounted at 3%. Monte Carlo simulation was used to calculate incremental cost-effectiveness ratios (ICERs). A willingness-to-pay (WTP) threshold of US$100,000 was used. Results: In terms of Medicare Advantage payer’s perspective (Table), docetaxel (D)+ADT was observed to provide additional 0.068 QALYs compared to ADT at an ICER of US$16,544 per QALY in high volume disease. Compared to D+ADT, abiraterone (AAP) triplet provided additional 1.03 QALYs at US$56,641 per QALY. Compared to AAP triplet, apalutamide (APA)+ADT provided additional 0.048 QALYs at US$5,846,248 per QALY in high volume disease. In low volume disease, D+ADT provided 0.45 more QALYs at US$20,690 per QALY compared to ADT alone. Compared to D+ADT, AAP triplet provided an additional 1.51 QALYS at US$44,267 per QALY. In terms of total paid commercial costs, AAP triplet provided an additional 1.19 QALYs compared to ADT at US$91,952 per QALY in high volume disease. In low volume, D+ADT provided additional 0.38 QALYs at US$22,058 per QALY compared to ADT. Compared to D+ADT, AAP triplet provided a 0.97 QALY gain at US$105,958 per QALY. Compared to AAP triplet, darolutamide (DARO) triplet provided a 0.47 QALY at US$689,196 per QALY. Compared to DARO triplet, APA+ADT provided an additional 0.49 QALYs at an ICER of US$971,389 per QALY. All other treatments (not reported here) were dominated. Conclusions: At the selected WTP of US$100,000 per QALY, AAP triplet therapy was most likely the cost-effective strategy in overall mCSPC population particularly in patients with high volume disease. However, these results should be interpreted with careful accounting for timing of metastases. [Table: see text]

643 Background: The FDA approval of enfortumab (EV) and pembrolizumab (Pembro) combination therapy as a first-line treatment for cisplatin-ineligible patients with locally advanced/metastatic urothelial carcinoma (la/mUC) was based on the EV-103 trial. We aim to assess the clinical response rate of this combination therapy in our institution's patients with locally advanced and metastatic UC. Methods: This retrospective cohort study included 20 patients diagnosed with locally advanced/metastatic UC(la/mUC) who were treated with EV-Pembro combination for at least 2 cycles, from June 2022 to August 2023 at the Mayo Clinic. Patients who were treatment naïve or who progressed one or more lines of therapy were included in the study cohort. Main outcome of interest included imaging-based best overall response rate in terms of complete (CR) and partial (PR) response, stable disease (SD), and progressive disease (PD). Results: Out of 20 patients, the number of males and females were 16 (80%) and 4 (20%) respectively; the median age was 77 years (IQR: 51-92). 3 (15%) of patients had involvement of upper urinary tract disease along with bladder cancer. The common sites of visceral metastasis at the time of initial presentation include liver 2(10%), lung 6(30%) and lymph nodes12(60%). Common toxicities of this regimen included rash, pruritis, peripheral neuropathy, fatigue, transaminitis, dysgeusia, and diarrhea. The treatment was stopped in 10 (50%) patients due to completion of planned therapy (achieved CR or proceeded with resection of residual disease) (30%), 5 patients due to progression (50%), 1 patient due to therapy side effects (10%) and in 1 patient due to death (10%). The objective response was 45% (N =9); 5 (25%) had PR, and 4 (20%) had CR. A total of 2 (10%) had SD while 2 (10%) experienced PD. Histological correlation with clinical benefit is shown in the table. Conclusions: EV-Pembro combination therapy shows promising responses in patients who have progressed after previous lines of therapy, consistent with previously published data on EV 201 in small cohorts. However, ongoing expansion of this cohort and data from larger studies will help further elucidate survival benefits and their correlation with genetic testing. [Table: see text]

639 Background: Immunotherapy combined with chemotherapy (IO/C) as the first-line management of locally advanced or metastatic urothelial carcinoma (LA/mUC) has been investigated in multiple trials with conflicting outcomes. Therefore, we conducted a meta-analysis of available trials to compare objective response rates (ORR) of this combination regimen, both in overall and in cisplatin-ineligible populations. Methods: EMABSE and MEDLINE were searched from 2000 through July 20th, 2023, to identify phase II and III clinical trials assessing IO, C or both in LA/mUC. Main outcome of interest was objective response rates (ORR) as defined in the included trials. An inverse variance random-effects meta-analysis was performed to estimate pooled ORR using the restricted maximum likelihood estimation method. Subgroup differences were assessed among IO/C, IO alone, and C alone. The threshold for statistical significance was established at 0.1. Results: Of 5975 citations identified, a total of 26 trials with a total of 4,628 participants were included in this systematic review. In the overall group, the ORR in IO/C trials (5 trials, 1,236 patients) was 44.70% (95% CI: 21.88%- 70.0%). In IO trials (7 trials, 2,189 patients), ORR was 23.68% (19.55%- 28.36%) and in C trials (26 trials, 4,628 patients) was 43.46% (37.43%-49.68%]). In the cisplatin-ineligible group, the ORR in IO/C trials (2 trials, 240 patients) was 60.06% (33.38%-81.86%), in IO trials (6 trials, 1,103 patients) was 26.15% (23.01%; 29.56%), and in C trials (8 trials, 767 patients) was 42.45% (35.67%-49.52%). In terms of subgroup differences, the difference in ORR was statistically significant between IO/C and IO trials (p= 0.0844) and between IO and chemotherapy trials (p< 0.0001) in the overall population. Similarly, we found a statistically significant difference in ORR between IO/C and IO (p= 0.0108) and between IO and chemotherapy trials (p< 0.0001) in the cisplatin-ineligible population. No statistically significant differences were observed between IO/C and C alone. Conclusions: First-line IO/C may achieve a better objective response compared to IO alone in patients diagnosed with locally advanced/metastatic UC. Although, there appears to be a trend of greater benefit with IO/C compared to C alone, the difference was not statistically significant. The results will be updated as soon data from new trials (CheckMate 901 and EV 302) becomes available which could offer new insights. [Table: see text]

627 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate recently approved to treat locally advanced or metastatic bladder cancer (la/mUC). Initial trials have shown promising response to EV in advanced urothelial cancers (UC), where prognosis is currently poor. Here, we report real-world experience using EV at a tertiary center. Methods: This study reports treatment details and outcomes in 92 patients (pts) that received at least one complete cycle of EV monotherapy in treatment of la/mUC. Treatment details include intent of cycle duration, 21 days (treatment on days 1 and 8) or 28 days (treatment on days 1, 8 and 15), dose reductions, and median number of cycles completed. Interruptions in treatment are reported as intentional (i.e. holding EV after achieving positive response) or unintentional (i.e. secondary to drug toxicity or other delay). Image-based best clinical response consists of progressive disease (PD), stable (SD), partial (PR), complete response (CR), and not evaluable (NE). Clinical benefit rate (CBR) is defined as either SD, PR, and CR outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Results: Patients mean age was 71.1 years (IQR: 66.8 - 78), 72 (79.2%) are male and 20 (20.8%) female, 89 (96.7%) pts received EV in the setting of metastatic UC, 3 (3.3%) in locally advanced UC. 13 (13.5%) pts were previously chemotherapy exposed, 9 (9.8%) were immunotherapy exposed, 60 (65.2%) were both chemo and immunotherapy exposed, and 11 (12.0%) received EV first line. 46 (50%) pts underwent 21-day treatment cycles, and 46 underwent 28-day treatment cycles. The median number of EV cycles was 3 (range 1-16) in the overall cohort, 3 in the 21-day cycle group, and 4 in the 28-day cycle group. 50 (54.3%) pts required dose reductions secondary to toxicity. 11 (12.0%) pts had planned interruptions, and 33 (35.9%) had unplanned interruptions. Best clinical response consisted of 24 (26.0%) pts with PD, 12 (13.0%) with SD, 25 (27.2%) with PR, 17 (18.5%) with CR, and 14 (15.2%) NE. CBR was 54 (58.7%) in the overall sample. CBR in the 21-day and 28-day cycle groups was identical at 27 (29.3%). EV therapy was discontinued most for cancer progression (34, 37.0%), therapy toxicity (18, 19.6%), and pt death (12, 13.0%). In 13 (14.1%) pts therapy is still ongoing. 73 (76.0%) pts had mild to moderate toxicities, and 19 (19.7%) reported severe toxicities that required hospitalization. Median OS in the total cohort was 11.01 months (95% CI: 8.51-14.6). Median PFS is 5.49 months (95% CI: 4.60-8.19). Conclusions: Real-world utilization of EV showed significant heterogeneity in administration patterns (21 days vs 28 days) and across a range of settings (first line, chemo exposed, IO exposed, chemo and IO exposed). Although EV has high response rates, more than 3/4th of patients suffered mild to moderate toxicities and 1/5th required hospitalization.

49 Background: Ductal carcinoma (DC) is the second most commonly encountered histologic variant of prostate cancer. Previous studies have described its molecular features and aggressive behavior, but few have explored the performance of PSMA PET/CT in the initial staging and follow-up of DC. Methods: To address this gap, we performed a single-institution retrospective analysis using the Mayo Clinic PSMA PET database. All patients receiving a PSMA PET/CT scan in the interval of January 1, 2021, to December 31, 2022, were eligible for inclusion. Cases were filtered and categorized by histology at the time of diagnosis to select for pure DAC and mixed ductal variants. Trained research personnel annotated disease- and treatment-related variables. A board-certified radiologist performed tumor burden segmentation with calculations of SUV max, total lesion SUV mean and volume, and total lesion uptake, and ascribed a miPSMA expression score. Results: We queried 1792 patients from our PSMA PET/CT registry and identified 32 (1.8%) patients with a pathologically confirmed DC, including 8 (25%) patients with pure ductal and 25 (75%) patients with mixed histology. The indication for PSMA PET/CT was biochemical progression or restaging for 29 (91%) patients and initial staging for 3 (9%) patients. The median (IQR) time from prostate cancer diagnosis to PSMA PET scan was 41.6 (11.5-64.7) months, during this time 50% (n= 16) of patients developed CRPC. At the time of the PSMA PET/CT scan, the median age was 70 years, the median (IQR) PSA was 0.5 ng/mL (0.2-2.6). The distribution of metastatic spread and quantitative imaging parameters from PSMA PET are shown in the Table. Conclusions: Despite low PSA at the time of imaging, PSMA PET/CT frequently detected high volume osseous and/or visceral metastases in patients with DC. However, it is noteworthy that more than 50% of patients with DC had a low miPSMA score (0-1). Additional studies are needed to better understand the performance of novel imaging modalities when evaluating variant prostate cancers. [Table: see text]

412 Background: Previously we have reported comparative effectiveness data regarding survival of first line (1L) treatment options in mRCC. However, it is not known how the life-prolonging frontline combinations compare to patient-reported outcomes. Methods: Electronic databases including MEDLINE and EMBASE were searched from each database’s inception through July 1st 2023. Phase III randomized controlled trials (RCTs) assessing 1L immune-checkpoint inhibitor (ICI) combination therapies for mRCC and reporting HrQoL were included. Small sample size adjusted standardized mean differences (SMD; Hedges’ g) with 95% confidence intervals (CI) were computed for global, physical, functional, and emotional QoL. Positive SMD indicated an improvement. A network meta-analysis was conducted to assess the comparative HrQoL across different treatment options. P-scores were computed to assess relative treatment rankings. Results: Of 5770 citations identified, five trials (nine references) were included in this analysis. Patient-reported outcomes have not been reported in the JAVELIN Renal 101 or COSMIC-313 trials yet. Global QoL was significantly improved with cabozantinib-nivolumab (CaboNivo) as compared to Nivo-ipilimumab (SMD 2.74, 95% CI 2.54; 2.93), lenvatinib-pembrolizumab (LenPem; 2.79, 2.53; 3.06), sunitinib (2.87, 2.72; 3.03), Pem-axitinib (PemAxi; 3.09, 2.89; 3.30) and atezolizumab-bevacizumab (AteBev; 3.24, 3.04; 3.45). Global QoL improvement was also observed with NivoIpi compared to sunitinib (0.14, 0.02; 0.25), PemAxi (0.36, 0.18; 0.54) and AteBev (0.51, 0.33; 0.68). Physical QoL improvement were consistent with CaboNivo. Likewise, LenPem significantly improved QoL compared to sunitinib (0.26, 0.04; 0.47), PemAxi (0.38, 0.13; 0.64) and NivoIpi (0.51, 0.27; 0.76). Significant functional QoL benefits were only observed with CaboNivo (0.32, 0.17; 0.48) and NivoIpi (0.19, 0.08; 0.31) compared to sunitinib. No significant mixed treatment comparisons were observed for emotional QoL, however, currently available data suggests that LenPem (rank 1) may potentially improve QoL (Table). Conclusions: CaboNivo and NivoIpi as 1L therapy may offer an improved overall HrQoL compared to other contemporary treatment options in mRCC. [Table: see text]