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Systemic treatments for penile squamous cell carcinoma (pSCC) are toxic and inefficient. Patient-based preclinical models are essential to study novel treatments.To establish a library of patient-derived tumor xenograft (PDX) models of human papillomavirus-positive (HPVEighteen tumor samples from 14 patients with recurrent or metastatic pSCC were implanted in nude mice. A biobank of PDX tumors was established after passaging of patient samples (F0) for three generations (F1, F2, F3) and was characterized using histopathology and targeted next-generation sequencing (tNGS). Single-nucleotide polymorphism fingerprinting was used to confirm PDX genealogy.The engraftment rate, overall growth rate, and pSCC histomorphology were checked for each PDX generation. Staining for p40 (a pSCC marker) and p16 (a surrogate for HPV infection) was performed for F0 samples. The mutational profile according to a validated panel of 96 cancer genes was determined for F0 and F3 samples and compared to a larger tNGS database.Including a previously established pilot model, 11 out of 18 tumor samples (61%) successfully engrafted in F1. The mean time from implantation in F1 to completion of F3 was 36 wk (standard deviation 18). Histological fidelity was demonstrated across generations. The patient mutational profiles were preserved in F3 and were representative of 277 pSCC samples in the Foundation Medicine database. The rapid progression of pSCC in patients from our selected high-risk cohort impeded the use of PDXs as avatars.We successfully established the first library of 11 PDX models of HPVWe established 11 animal models based on tumor tissue from patients with penile cancer. These models could play a vital role in selection of novel treatments according to genetic mutations. In the future, therapies with confirmed preclinical effects may have a profound impact on the development of personalized treatments in penile cancer.

Background: The term “financial toxicity” or “hardship” is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening. Methods: This cross-sectional survey–based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively. Results: Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867–0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941–0.998; P=.039). Conclusions: Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.

Background Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort. Methods Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a 324-gene hybrid-capture-based method which also calculates tumor mutational burden (TMB) and determines microsatellite status (MSI). Results Of the cohort, 7447 (85.3%) were EUR, 541 (6.2%) were AFR, 461 (5.3%) were of AMR, 74 (0.85%) were SAS, and 205 (2.3%) were EAS. When compared with EUR, TERT GAs were less frequent in SAS (58.1% vs. 73.6%; P = .06). When compared with non-SAS, SAS had less frequent GAs in FGFR3 (9.5% vs. 18.5%, P = .25). TERT promoter mutations were significantly less frequent in EAS compared to non-EAS (54.1% vs. 72.9%; P < .001). When compared with the non-EAS, PIK3CA alterations were significantly less common in EAS (12.7% vs. 22.1%, P = .005). The mean TMB was significantly lower in EAS vs. non-EAS (8.53 vs. 10.02; P = .05). Conclusions The results from this comprehensive genomic analysis of UCB provide important insight into the possible differences in the genomic landscape in a population level. These hypothesis-generating findings require external validation and should support the inclusion of more diverse patient populations in clinical trials.

Laparoscopic prostatectomy and robot-assisted laparoscopic prostatectomy are common procedure performed for the treatment of localized prostate cancer. Port site and peritoneal seeding is an exceedingly rare but known complications associated with this procedure. We present a case of a 71-year old male with low-intermediate risk prostate adenocarcinoma who underwent a robot-assisted laparoscopic prostatectomy. Pathology at that time was negative for extraprostatic extension, seminal vesicle invasion, or margins. Seven months later, the patient presented with gross hematuria and was found to have multiple superficial tumors of the bladder urothelium consistent with high-grade papillary urothelial carcinoma. He then began to experience increasing lower abdominal pain and a palpable, right anterior abdominal mass. Computed tomography-guided biopsy revealed high-grade papillary urothelial carcinoma which strongly suggests peritoneal seeding from his recent robot-assisted laparoscopic prostatectomy. Despite its rarity, the morbidity associated with this phenomenon could help justify a recommendation of careful pathologic examination of each prostate specimen for a second urothelial primary with subsequent cystoscopy if one is found.

Introduction Patients diagnosed with stage II nonseminomatous germ cell tumors (NSGCT) often receive chemotherapy as primary treatment which exposes patients to immediate and long-term risks of chemotherapy. These risks can be avoided by proceeding to primary retroperitoneal lymph node dissection (RPLND) when a high suspicion of pure metastatic teratoma in the retroperitoneum (RP) exists. We propose that all stage II NSGCT patients with pure testicular teratoma, normal serum tumor markers, and with RP cystic metastases on imaging can safely be treated with primary RPLND. Methods We identified 14 patients found to have 100% teratoma in orchiectomy specimens, negative serum tumor markers, and with metastatic cystic RP disease. Disease recurrence was also evaluated to establish efficacy of treatment. Results All 14 patients were chemotherapy naive and found to have pure metastatic teratoma. All patients were IGCCCG good risk with stage IIA (21.4%), IIB (35.7%), and IIC (42.9%) disease. Median RP mass size was 4.9 cm (1.8 to 24 cm). All patients underwent a RPLND finding 100% teratoma in the RP. Median follow-up was 6.9 years. One patient (7.1%) who received a right modified template RPLND relapsed in the left RP 10.2 years later who underwent treatment and has been disease free for over 5.5 years. Conclusions Primary surgical treatment in this cohort of pure metastatic teratoma resulted in good clinical outcomes and the ability to avoid unnecessary induction chemotherapy. It is important that contrary to previous suppositions, patients with pure teratoma of the testis can independently metastasize with teratoma only, without metastatic carcinoma.

In patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medical need.In this comparative comprehensive genomic profiling (CGP) study, genomic alterations (GAs), and immuno-oncology (IO) biomarkers have been analyzed.Within the Foundation Medicine database, 143 cases with centrally reviewed pure ACB, 2142 with pure urothelial carcinoma (UC), and 83 with pure SCC were subjected to CGP. All patients developed advanced disease following a primary diagnosis of bladder cancer.CGP using a hybrid capture-based assay and immunohistochemistry (IHC).Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA, and microsatellite instability (MSI) was determined on 114 loci. Programmed cell-death ligand-1 (PD-L1) expression was determined by IHC (Ventana SP-142 assay), with1% tumor cells (TCs) or tumor-infiltrating lymphocytes (TILs) scoring positive.Pure ACB patients were younger and more often female than pure UC and pure SCC patients. UC and SCC had a significantly higher median TMB than ACB (p0.001). Rare CD274 (PD-L1) amplification cases were more frequently seen in SCC than in UC (5% vs 1%), and were not seen in ACB. MSI high status was very uncommon in all tumor types (0-1%). The frequencies of PD-L1 expression in both TCs and TILs was higher in UC and SCC (both 30%) than in ACB (18%). The results are limited by their retrospective nature and lack of clinical data annotation.Deep sequencing revealed significant differences in IO biomarkers among the three major subtypes of bladder carcinomas. UC and SCC revealed higher frequencies of PD-L1 expression and higher TMB than ACB, and SCC has the highest frequency of CD274 amplification. The presence of pure SCC features should not disqualify patients for inclusion in IO trials.Tumor samples from patients diagnosed with advanced pure adenocarcinoma of the bladder (ACB) or pure squamous-cell carcinoma (SCC) have been analyzed in terms of frequency of putative immunotherapy biomarkers. The results indicated that pure SCC of the bladder was characterized by genomic features that portend similar response possibilities to immunotherapy compared with the classical pure urothelial carcinoma. Conversely, for pure ACB there might be different therapeutic opportunities, such as targeted therapies against peculiar genomic alterations in selected patients.

IntroductionElectronic cigarette (e-cigarette) smoking and similar novel smoking modalities have raised questions about their impact on various cancers compared with traditional forms of tobacco smoking. Tobacco smoking has been proven to increase the risk of many cancers, including lung (LCa) and bladder (BCa) cancer. Currently, there is little data on how e-cigarette smoking impacts the incidence of these cancers. We investigated whether any disparities exist in the prevalence of LCa and BCa between various smoking histories using a US nationally representative data source.MethodsThis cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database between 2016-2018. Primary endpoint was self-reported occurrence of LCa and BCa diagnosis. Multivariable logistic regression analyses assessed possible association of various covariates with diagnosis of these cancers. ResultsPrevalence of BCa and LCa was higher in all smoking histories compared to never smokers. Patients with a history of e-cigarette smoking vs. no history of e-cigarette smoking were significantly younger at BCa diagnosis (56.87 [±9.86] vs. 65.00 [±12.60] years, p=0.001). Multivariable logistic regression models showed that a history of cigarette smoking and e-cigarette smoking individually and exclusively was associated with increased ORs of 2.476 (p=ConclusionsCompared to never smokers, e-cigarette smoking history was associated with increased risk of LCa and BCa development. Additional studies are needed to better define the public health effects of these novel and unregulated products.

258 Background: Tumors harboring 2 or more PIK3CA Short variants (SV) (“Multi-hit”) have been described in breast cancer as linked to enhanced clinical outcome from anti-PIK3CA targeted therapies including alpelisib and investigational agents in clinical trials. The landscape and clinical implications of multi-hit PIK3CA alterations in other tumors, including in CAPC, are underexplored. Methods: 19,978 CAPC samples underwent hybrid capture based comprehensive genomic profiling (CGP) to evaluate all classes of GA and determine tumor mutational burden (TMB), microsatellite instability (MSI), genomic ancestry, signature and loss of heterozygosity (gLOH). Tumor cell PD-L1 expression was determined by IHC (Dako 22C3). Results: 18,741 (93.8%) CAPC were PIK3CA wild type (WT), 1,155 (5.8%) featured a single PIK3CA SV and 82 (0.4%) featured multi-hit PIK3CA SVs. The median ages of CAPC patients with single hit (69.1 yrs) or multi-hit (68.7 yrs) PIK3CA SV were older than the PIK3CA WT (67.6 yrs) CAPC (p

564 Background: CDH1 mutated UBCs are characterized by plasmacytoid histology and are associated with an aggressive clinical course at the time of diagnosis. Methods: Cohort 1: 6,676 clinically advanced UBC patients (pts) underwent comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA), microsatellite instability (MSI), tumor mutational burden (TMB), and genomic loss of heterozygosity (gLOH, high ≥16%). Predominant genetic ancestry was determined using a SNP-based approach and classified as one of the 5 categories: African (AFR), European (EUR), Central and South American (AMR), South Asian (SAS), or East Asian (EAS). Cohort 2: 586 UBC pts underwent a RWCOS using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine urothelial clinico-genomic database (FH-FMI CGDB). The de-identified data originated from approximately 280 US cancer clinics (~800 sites of care) Jan 2011-Apr 2022. Differences in real-world progression-free survival (rwPFS) and overall survival (rwOS) were evaluated by Cox proportional hazard models. Results: Cohort 1: 217 (3.3%) of UBC had a CDH1 short variant (SV) mutation with 65.2% featuring plasmacytoid histology. When compared with CDH1 wild-type (WT) UBC, the CDH1-mutated UBC had similar age, gender, and genetic ancestry. The CDH1-mutated UBC featured a higher frequency of MSI (2.7% vs 0.8%; p=.002), mean TMB (14.8 vs 9.9 mut/Mb p

566 Background: Given the recent approval in lung cancer for the first anti-HER2 targeted therapy directed against activating kinase domain exon 20 ERBB2 insertion mutations, considerable interest has arisen in targeting additional locations in the ERBB2 gene in other tumor types. Methods: 5,485 UBC samples were sequenced using a hybrid capture-based comprehensive genomic profiling (CGP) assay to assess all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genomic loss of heterozygosity (gLOH), trinucleotide signatures and predominant genetic ancestry. Statistical comparisons utilized the Bonferroni correction. Results: 548 (10.0%) of UBC featured ERBB2 gene amplification (amp) and 219 (4.0%) featured an ERBB2 ECD+ sequence mutation (74% S310F and 26% S310Y). ERBB2 ECD+ mutations and ERBB2 amplification were mutually exclusive. 16.4% of ERBB2 ECD+ UBC had more than one E RBB2 sequence mutation. Central pathology review of the 219 ERBB2 ECD+ UBC revealed that 63 (28.8%) featured a micropapillary histologic appearance (MPUC). ERBB2 ECD+ UBC featured more patients with European ancestry than both ERBB2 WT (90.9% vs 84.2%; p=.03) and ERBB2 amp (90.9% vs 83.2%; p=.04). ECD mut+ UBC also featured lower association with African ancestry than ERBB2 amp (2.7% vs 7.8%; p=.04) and lower frequency of gLOH > 16% (9.3% vs 19.1%; p=.04). MSI-High status was similar and rare in all 3 groups (range 0 to 0.9%). ERBB2 ECD+ UBC had a higher frequency of APOBEC signature than ERBB2 amp (82.9% vs 72.4%; p=.03). TMB > 10 mut/mb was higher in ERBB2 amp (49.2% vs 31.4%; p

4 Background: TMB has emerged as a major biomarker of efficacy in immune checkpoint inhibitor (ICPI) therapies in the neoadjuvant, adjuvant and metastatic disease setting in a wide variety of malignancies, but not in PSCC. Methods: 397 clinically advanced (local major recurrence and/or metastatic disease) PSCC underwent hybrid capture-based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. Trinucleotide mutation signatures were evaluated (Alexandrov, et al. 2013). Genome-wide loss of heterozygosity (gLOH) was determined using validated pipelines and excluding whole-arm and whole-chromosome events. TMB was categorized into three cohorts: 20 muts/Mb (very high). Tumor cell PD-L1 expression was determined by IHC (Dako 22C3) and defined as tumor proportion score (TPS) >1. The presence of HPV16/18 was determined by next generation sequencing (NGS). Statistical comparisons were corrected for multiple comparisons using the Bonferonni method. Results: There were 339 (85.4%) TMB low, 40 (10.1%) TMB 10-19 and 18 (4.5%) TMB very high PSCC cases in this study. The mean age of PSCC with very high TMB at 70.1 yrs was older than for TMB low at 63.4 yrs (p=.08). There were no significant differences in genomic ancestry among the 3 groups. The TMB 10-19 and TMB very high tended to feature an APOBEC genomic mutational signature more than the TMB low PSCC cases (74 and 76% vs 44%). MSI high status was absent in the TMB low PSCC, but was present in 7.5% of the TMB 10-19 and 11.8% of the TMB very high cases. gLOH levels above 16% were similar in all 3 groups and ranged from 6.2 to 9.4%. GA associated with differences in TMB status in the PSCC cases included higher PIK3CA GA in TMB 10-19 (40.0%) vs TMB low (18.3%; p=.035) and TMB very high (66.7%) vs TMB low (p=.0002). CDKN2A GA were higher in TMB low (45.7%) than in the combined TMB 10-19 + very high (25.9%; p=.049). GA in KMT2D were higher in the combined TMB 10-19 + very high (29.3%) than the TMB low PSCC (7.7%; p=0002). FGFR3 GA were similar in all 3 groups. PD-L1 expression was not significantly different among the 3 groups with TMB low (78.3%), TMB 10-19 (64.2%) and TMB very high (54.5%). HPV identification was more frequent as TMB increased: 28.3% for the TMB low, 50.0% for the TMB high and 58.8% for the TMB very high groups. Conclusions: The evaluation of PSCC by CGP based on TMB levels revels significant differences in biomarkers for the near 15% of cases that have TMB >10 muts/Mb. Further study of TMB as a biomarker in ICPI-based clinical trials for advanced PSCC appear warranted.

567 Background: UBC is the 10th most common cancer worldwide, with more than 550,00 new cases annually (WHO, International Agency for Research on Cancer, 2020). Rates vary by regions of the world, explained in part by the fact that different genetic ancestries demonstrate varying germline genetics, environmental exposures, and social risk factors. Methods: 8,728 UBC samples underwent hybrid capture-based comprehensive genomic profiling (CGP) to determine all classes of genomic alterations (GA), microsatellite instability (MSI) status, tumor mutational burden (TMB), and genomic trinucleotide signature. Predominant genetic ancestry was determined using a SNP-based approach using an algorithm trained on the 1000 Genomes data (Connelly et al. AACR 2018). Ancestry was classified as one of the five following categories: African (AFR), European (EUR), Central and South American (AMR), South Asian (SAS), or East Asian (EAS). Results: Of the cohort, 7,447 (85.3%) were EUR, 541 (6.2%) were AFR, 461 (5.3%) were of AMR, 74 (0.85%) were SAS, and 205 (2.3%) were EAS. Age, gender, genomic signature distributions, and MSI status (range 0.9%-1.5%) were similar in all cohorts. The frequency of TMB >10 mutations/Megabase was similar in all cohorts (range 30.7%-39.1%) as was the median TMB (6.3 mutations/Megabase for all). At 67.6%, TP53 was the most frequent GA in SAS cohort. When compared with the non-SAS cohort, TERT GA were lower in the SAS cohort (58.1% vs 72.6%; p=0.06) as were GA in FGFR3 (9.5% vs 18.5%, p=0.25). In the EAS cohort, at 59.0%, GA in TP53 were the most common. TERT mutations were significantly lower in EAS compared to the non-EAS cohort (54.1% vs 72.9%; p

PURPOSE: We investigated the association between race and FT among previous patients with cancer. Studies show that patients with cancer experience financial toxicity (FT) because of their cancer treatment. METHODS: Data on individuals with a cancer history were collected in this cross-sectional study during 2012, 2014, and 2017, from the US Health Information National Trends Survey. This survey is conducted by mail with monetary compensation as an incentive. We specifically assessed responses to two questions: Has cancer hurt you financially? Have you been denied health insurance because of cancer? Multivariable logistic regression analyses were used to assess the associations between these questions and race. RESULTS: Of 10,592 individuals participating, 1,328 men and women (12.5%) with a cancer history were assessed. Compared with Blacks, Whites were found to have a higher rate of insurance (95.4% v 90.0%), were more likely to receive cancer treatment (93.9% v 85%), and had a higher rate of surgical treatment than Blacks (77% v 60%), Hispanics (55%), and others (77%, 60%, 55%, and 74.2%, respectively, P < .001). On multivariable analysis, Blacks were more than five times as likely to be denied insurance (odds ratio, 5.003; 95% CI, 2.451 to 10.213; P < .001) and more than twice as likely to report being hurt financially because of cancer (odds ratio, 2.448; 95% CI, 1.520 to 3.941; P < .001) than Whites. Of all cancer groups analyzed (genitourinary, gynecologic, gastrointestinal, and breast), genitourinary malignancies were the only group in which the rate of reporting being hurt financially varied in a statistically significant manner (Whites 36.7%, Hispanics 62.5%, and Blacks 59.3%, P = .004). CONCLUSION: Our data suggest that race is significantly associated with FT because of cancer. Awareness of racial inequality with regards to FT should be raised among health care workers.

Simple Summary Clinically advanced pheochromocytomas and paragangliomas are a rare form of endocrine malignancy which can occur in familial and sporadic clinical settings and feature a variety of genomic alterations. Comprehensive genomic profiling (CGP) was performed to characterize the genomic alterations (GA) in clinically advanced disease to enable the search for potential therapy targets. Although the GA/tumor is relatively low for clinically advanced disease, CGP can reveal important potential targets for therapy in the metastatic setting including RET, NF1 and FGFR1. Based on this data, further study of CGP as a method of developing precision therapies for clinically advanced disease appears warranted. Abstract Patients with clinically advanced paragangliomas (CA-Para) and pheochromocytomas (CA-Pheo) have limited surgical or systemic treatments. We used comprehensive genomic profiling (CGP) to compare genomic alterations (GA) in CA-Para and CA-Pheo to identify potential therapeutic targets. Eighty-three CA-Para and 45 CA-Pheo underwent hybrid-capture-based CGP using a targeted panel of 324 genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined. The GA/tumor frequencies were low for both tumor types (1.9 GA/tumor for CA-Para, 2.3 GA/tumor for CA-Pheo). The most frequent potentially targetable GA in CA-Para were in FGFR1 (7%, primarily amplifications), NF1, PTEN, NF2, and CDK4 (all 2%) and for CA-Pheo in RET (9%, primarily fusions), NF1 (11%) and FGFR1 (7%). Germline mutations in known cancer predisposition genes were predicted in 13 (30%) of CA-Pheo and 38 (45%) of CA-Para cases, predominantly involving SDHA/B genes. Both CA-Para and CA-Para had low median TMB, low PD-L1 expression levels and none had MSI high status. While similar GA frequency is seen in both CA-Para and CA-Para, germline GA were seen more frequently in CA-Para. Low PD-L1 expression levels and no MSI high status argue against strong potential for novel immune checkpoint inhibitors. However, several important potential therapeutic targets in both CA-Para and CA-Para are identified using CGP.

The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is limited by lack of biomarkers to optimize patient selection. We have recently identified the tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors. Highly variable mutations of TSC1 have been previously identified in bladder cancer and correlate with sensitivity to the Hsp90 inhibitors. Here we showed loss of TSC1 leads to hypoacetylation of Hsp90-K407/K419 and subsequent decreased binding to the Hsp90 inhibitor ganetespib. Pharmacologic inhibition of histone deacetylases (HDACs) restores acetylation of Hsp90 and sensitizes Tsc1-mutant bladder cancer cells to ganetespib, resulting in apoptosis. Our findings suggest that TSC1 status may predict response to Hsp90 inhibitors in patients with bladder cancer, and co-targeting HDACs can sensitize tumors with Tsc1 mutations to Hsp90 inhibitors.

5063 Background: NEPC is a high-grade aggressive form of prostate cancer. We queried whether RB1 mutation status would impact the genomic features of NEPC in RB1 mutated vs non-mutated cases. Methods: From a series of 13,496 cases of clinically advanced PC, we identified 415 cases (3.1%) with a diagnosis of small cell PC or NEPC as determined by the submitting physician. They were sequenced using a hybrid capture-based FDA-approved clinical genomic profiling (CGP) assay to detect all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on 0.8 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 loci. PD-L1 expression was determined by IHC (Dako 22C3) with low tumor cell positive staining 1-49% and high staining ≥50% expression. Results: 253 (61%) of NEPC feature GA in RB1 (RB1 mut+). This contrasts with a 5.8% frequency of RB1 GA in the non-NEPC (P

e16535 Background: Immunohistochemistry (IHC) to determine PD-L1 expression level has been used as a biomarker to predict immune checkpoint inhibitors response in UCB. We hypothesized that the GA profiles would differ between UCB featuring high vs negative PD-L1 expression. Methods: 102 cases of advanced UCB with known PD-L1 tumor cell expression underwent hybrid-capture based comprehensive genomic profiling to evaluate all classes of genomic alteration (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Tumor cell (TC) PD-L1 expression was determined by IHC (Dako 22C3). Only PD-L1 high (H) (≥50% TC expression) and negative (N) (0% TC expression) cases were included in this study. Results: Overall, only 2 (8.3%) of the 24 PD-L1H UCB featured CD274 ( PD-L1) amplification (mean 19 copies) and none of 78 PD-L1N had CD274 amplification (P = .05). The gender, age and GA per tumor frequencies were similar in the groups. When compared with the PD-L1H UBC cases, FGFR3 GA were significantly more frequent in the UBC PD-L1N cases (p = .02). Currently “untargetable” GA that were more frequent in the PD-L1H UBC, but did not reach significance, included TP53, TERT and RB1. MTAP loss, a potential target for PRMT5 and MTA2 inhibitors, were 3X more frequent in the PD-L1N UBC. ERBB2 amplification and ERBB3 and PIK3CA short variant (SV) GA were more frequent in the PD-L1N UBC with differences not reaching significance. The mean gLOH scores were similar in both groups. Other ICPI-associated potential biomarkers, including MSI status, TMB level and GA in PBRM1, STK11 and MDM2 were not significantly different in the groups. For UCB cases where a mutational signature could be determined, 15/33 (45%) of PD-L1H and 34/112 (30%, p = 0.14) of PD-L1N UCB featured an APOBEC gene signature; 79% of PD-L1H and 83% of PD-L1N featured European ancestry (p = 0.61). Conclusions: PD-L1H and PD-L1N subtypes of UCB differ in their genomic profiles. PD-L1N UCB features greater frequencies of potentially “targetable” GA, including FGFR3, ERBB2, ERBB3 and PIK3CA. PD-L1 IHC may thus not only play a role in the selection of ICPI for advanced UCB but also in designing trials that may combine ICPI with targeted therapies.[Table: see text]

e17014 Background: Prostate Specific Antigen (PSA) testing can improve early prostate cancer detection. However, numerous factors can influence patients’ willingness and ability to undergo PSA testing. Methods: We performed a cross-sectional study investigating the impact of various degrees of ischemic heart disease (IHD) on PSA testing. We assessed 3,822 male respondents aged 55-75 from the 2018 year of the National Health Interview Survey (NHIS). Men were stratified according to the degree of IHD (none, history of angina pectoris (AP), history of myocardial infarction (MI), or history of neither, but with a diagnosis of IHD). Multivariable logistic regression analysis was used to assess the relationship between IHD and being tested for PSA, adjusting for known cofounders. Results: Multivariable logistic regression demonstrated that males with a history of IHD (no MI or AP) were more likely to have ever been PSA tested than males without IHD (p = 0.012, OR = 1.630, 95% CI 1.115-2.383), as seen in Table. Additionally, older age (p < 0.001), having a partner (vs. no partner p < 0.001), homosexual sexual orientation (vs. heterosexual orientation p = 0.007), and a history of cancer (vs. no history p < 0.001) all increased likelihood of being PSA tested. In contrast, Asian race (vs. White, p = 0.001), and being a current smoker (vs. no smoking history, p < 0.001) decreased the likelihood. Interestingly, males with a history of a symptomatic IHD (MI or AP) were not shown to be more likely to undergo PSA testing. Conclusions: Our results suggest that males with non-symptomatic IHD are more likely to be PSA tested. Males with symptomatic IHD do not seem to undergo more PSA screening, perhaps due to lower suggested life expectancy. Awareness of discrepancies in PSA testing in men with IHD should be raised. Table - Multivariable logistic regression analyses demonstrating relationships with likelihood of being PSA tested.[Table: see text]

4550 Background: FLCN is a tumor suppressor gene associated with cutaneous hair follicle development. FLCN germline mutations are linked to inherited chrRCC in the Birt-Hogg-Dube (BHD) syndrome. We queried whether clinically sporadic chrRCC featured FLCN mutations by comparing the genomic profiles of chrRCC with nonchrRCC. Methods: 109 chrRCC and 5,862 nonchrRCC underwent hybrid-capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: Patients (pts) with chrRCC were more frequently female (37 [34%] vs. 1,817 [31%]) and younger than pts with nonchrRCC (median age 58 vs 62 years, p

e18558 Background: Research has shown that the COVID-19 pandemic has reduced access to cancer treatment and care for patients, especially for COVID-19 patients. Methods: We investigated the impact of COVID-19 testing on access to cancer care. A US based cross sectional study was conducted on 2,393 cancer patients using data from the 2020 National Health Interview Survey. Multivariable logistic regression was used to assess associations between COVID-19 testing and likelihood of receiving cancer treatment or other cancer care during the pandemic. Results: Patients who reported ever being tested for COVID were on average younger (66.9 vs 69.3, p

4568 Background: Urothelial bladder carcinomas (UBC) with genomic alterations (GA) in the Fibroblast Growth Factor Receptor ( FGFR) genes have been postulated to be less responsive to immune checkpoint inhibitors (ICI). Immune microenvironment of these tumors could be altered due to suppression of interferon signaling pathways. Here, we present comprehensive genomic profiling (CGP) of FGFR altered UBC to study the underlying immunogenomic mechanisms of response and resistance. Methods: 4,035 UBC underwent hybrid capture based CGP. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined using 114 loci. Programmed death ligand (PD-L1) expression in tumor cells was assessed by IHC (Dako 22C3). Results: 894 (22%) of UBC featured FGFR GA ( FGFR1 3.7%; FGFR2 1.1%; FGFR3 17.4%). Gender and age distribution was similar in all groups. FGFR3 cases had lower GA/tumor and 14.7% GA were fusions. ERBB2 amplification was significantly higher in FGFR1/2 altered UBC compared with FGFR3 altered UBC. MTOR pathway GA were highest in FGFR3 altered UBC. FGFR3 altered UBC featured significantly higher frequencies of biomarkers predicting resistance to ICI including lower TMB, lower PD-L1 expression and higher frequencies of GA in MDM2. FGFR3 driven UBC also features significantly higher frequencies of CDKN2A/B loss and MTAP loss which have also recently been linked to IO drug resistance. Conclusions: UBC harboring FGFR GA have increased frequency of alterations that have been linked to ICI resistance. Further evaluation of FGFR-based biomarkers in UBC clinical trials focused on the assessment of the patient response to ICI appears warranted. [Table: see text]

BACKGROUND Patients with disabilities represent a unique minority population. The incidence of prostate-specific antigen (PSA) testing among this population is unknown. OBJECTIVE To compare PSA testing rates and associated predictors among men with and without reported disabilities in the USA. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of the Health Information National Trends Survey (HINTS) for the years 2012, 2013, 2017 and 2019 was conducted in men with reported disabilities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Baseline demographics of the entire cohort were stratified based on their reported disabilities (none, disabled, deaf, and blind). Each disability was compared separately and in combination with the cohort without disabilities. Multivariable logistic regression models determined clinically significant predictors of PSA testing in men with disabilities compared with those without. RESULTS AND LIMITATIONS Overall, 782 (15%) men with disabilities were compared with 4569 (85%) men without disabilities. The former cohort was older with a median (interquartile range) age of 65 (56-75) versus 57 (43-67) yr (p < 0.001). On multivariable analysis, men with any disability were less likely to undergo PSA testing (odds ratio 0.77, 95% confidence interval 0.62-0.96, p = 0.018). Variables associated with increased PSA testing included age, having a health care provider, health insurance, and living with a partner. CONCLUSIONS Inequalities in PSA testing exist among men with disabilities in the USA, especially among the deaf and blind, being less likely to undergo PSA testing. Further research is required to identify and deal with any obstacles in the implementation of equal PSA testing in this unique population. PATIENT SUMMARY In the USA, men with reported disabilities are less likely to undergo PSA testing than patients without reported disabilities.

Penile squamous cell carcinoma (PSCC) can be a devastating disease when major local recurrences and distant spread take place. In the modern era of targeted and immunotherapy approaches to cancer treatments, recent successes in the treatment of other genitourinary cancers has spurred the use of comprehensive genomic profiling evaluations using next-generation sequencing methods designed to uncover new routes of therapy for PSCC. In this chapter, the evidence of genomic differences between HPV-positive and HPV-negative clinically advanced PSCC is compared with a series of previously published studies considering the impact of molecular testing on PSCC treatment selection and clinical outcome. The genomic findings in PSCC are also compared and contrasted with those found in men with primary urethral SCC.

PURPOSE To develop an artificial intelligence (AI)–based model for identifying patients with lymph node (LN) metastasis based on digital evaluation of primary tumors and train the model using cystectomy specimens available from The Cancer Genome Atlas (TCGA) Project; patients from our institution were included for validation of the leave-out test cohort. METHODS In all, 307 patients were identified for inclusion in the study (TCGA, n = 294; in-house, n = 13). Deep learning models were trained from image patches at 2.5×, 5×, 10×, and 20× magnifications, and spatially resolved prediction maps were combined with microenvironment (lymphocyte infiltration) features to derive a final patient-level AI score (probability of LN metastasis). Training and validation included 219 patients (training, n = 146; validation, n = 73); 89 patients (TCGA, n = 75; in-house, n = 13) were reserved as an independent testing set. Multivariable logistic regression models for predicting LN status based on clinicopathologic features alone and a combined model with AI score were fit to training and validation sets. RESULTS Several patients were determined to have positive LN metastasis in TCGA (n = 105; 35.7%) and in-house (n = 3; 23.1%) cohorts. A clinicopathologic model that considered using factors such as age, T stage, and lymphovascular invasion demonstrated an area under the curve (AUC) of 0.755 (95% CI, 0.680 to 0.831) in the training and validation cohorts compared with the cross validation of the AI score (likelihood of positive LNs), which achieved an AUC of 0.866 (95% CI, 0.812 to 0.920; P = .021). Performance in the test cohort was similar, with a clinicopathologic model AUC of 0.678 (95% CI, 0.554 to 0.802) and an AI score of 0.784 (95% CI, 0.702 to 0.896; P = .21). In addition, the AI score remained significant after adjusting for clinicopathologic variables ( P = 1.08 × 10−9), and the combined model significantly outperformed clinicopathologic features alone in the test cohort with an AUC of 0.807 (95% CI, 0.702 to 0.912; P = .047). CONCLUSION Patients who are at higher risk of having positive LNs during cystectomy can be identified on primary tumor samples using novel AI-based methodologies applied to digital hematoxylin and eosin–stained slides.

INTRODUCTION AND OBJECTIVE:Advances in artificial intelligence (AI) techniques have allowed for the development of prognostic models using digital images of pathology slides. In this study we use d...

21 Background: The term ‘financial toxicity’ or ‘hardship’ is used to describe the financial problems patients experience due to high out-of-pocket costs for their healthcare. Financial toxicity in the context of cancer treatment is an area of recent study due to the significant costs associated with these treatments, but little is known about the effect of financial toxicity on cancer prevention. We examined the effects of financial toxicity on the utilization of screening tests for prevalent cancers, including prostate and colon cancer, using a US nationally representative survey-based data source. We hypothesized that patients with more financial hardship would show an association with decreased prevalence of prostate and colon cancer screening. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database from January – December 2018. A financial hardship score between 0 and 1 was formulated by summarizing the responses from ten financial toxicity questions including if in the past 12 months one was unable to afford prescription medication or healthcare; or if one had to skip or take less medicine to save money. A higher score was associated with a worse financial hardship score. The primary outcomes of the study were self-reported occurrence of PSA blood testing for prostate cancer screening, and occurrence of colonoscopy for colon cancer screening. Results: As shown in table, a higher financial hardship score was associated with a decreased odds ratio for having a PSA test of 0.916 (95% CI 0.867-0.967, p=0.002) and colonoscopy of 0.969 (95% CI 0.941-0.998, p=0.039). Conclusions: Worse financial hardship is associated with a decreased probability of having PSA or colonoscopy screening tests. Awareness of this specific toxicity needs to be raised, examining the association of financial toxicity and screening of prostate, colon, and other additional cancers. [Table: see text]

56 Background: Mental illness is a growing issue in the USA. More individuals continue to be diagnosed with illnesses such as depression and anxiety and placed on necessary medications. Studies have shown that the psychological makeup of an individual greatly impacts their health behavior and usage of preventative measures. However, there is limited research on the effect of anxiety and depression on PSA testing. This study explores the associations between the use of anxiety and depression medications and PSA testing. Methods: We used data from the National Health Interview Survey during the year 2018, and assessed responses to the question “Have you ever had a PSA test?” and “What is the number of PSA tests you had in the last 5 years?”. Responses were stratified by whether men were taking medications for anxiety, depression, both or none. We performed multivariable logistic regression analysis to define adjusted odds ratios of undergoing PSA testing adjusting for relevant socio-economic and demographic parameters. Results: Among the 5,035 male participants, 89.4% did not take any medication, 2.9% reported they took anxiety medication, 2.1% took depression medication and 5.5% took both medications. There was a significantly higher rate of PSA testing in men who took medications for both anxiety and depression compared to men taking no medications (p=0.002). Furthermore, the average number of PSA tests in the last 5 years was highest in the group of men taking both medications ( p < 0.0001). Multivariable analysis showed that men who took medications for both depression and anxiety were more likely to undergo PSA testing in comparison to men, not on any of these medications (OR=1.755, p=0.001). The multivariable analysis also showed that age, living with a spouse, and prior cancer history were associated with an increased likelihood of PSA testing while being a minority, living in the south of the USA, and being a current smoker was associated with a lower likelihood of undergoing PSA testing. Conclusions: Taking both anxiety and depression medications in men may be associated with a higher likelihood of undergoing PSA testing. Despite obvious limitations of this analysis including its retrospective nature and recall bias, this association needs to be further explored, especially due to rising use of these medication in the current era of the COVID-19 pandemic.[Table: see text]

TPS593 Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) unresponsive to intravesical bacillus Calmette–Guérin (BCG). TAR-200 is an intravesical drug delivery system for local continuous release of gemcitabine within the bladder. The current study will assess the rate of complete response (CR) upon treatment with TAR-200 + systemic cetrelimab (CET [anti–PD-1 antibody]), TAR-200, and CET in BCG-unresponsive participants with HR-NMIBC who are ineligible for or decline radical cystectomy (RC). Methods: SunRISe-1 (NCT04640623) is an open-label, parallel-group, multicenter phase 2b study designed to assess the efficacy and safety of TAR-200 + CET, TAR-200 alone, and CET alone in participants with BCG-unresponsive HR-NMIBC. Eligible participants are aged ≥ 18 years with ECOG PS 0, 1, or 2 and recurrent or persistent histologically confirmed HR-NMIBC (carcinoma in situ) with or without papillary disease (T1, high-grade Ta), who have been diagnosed within 12 months of last BCG treatment and are ineligible for or declined RC. Participants (N≈200) are randomized 2:1:1 to receive TAR-200 + CET (Cohort 1, n≈100), TAR-200 (Cohort 2, n≈50), or CET (Cohort 3, n≈50). In Cohorts 1 and 2, participants receive intravesical TAR-200 every 3 weeks through Week 24, and every 12 weeks thereafter until Week 96. In Cohorts 1 and 3, participants receive CET until Week 78. Primary disease assessments (cystoscopy, urine cytology, transurethral resection of bladder tumor [TURBT], and magnetic resonance imaging/computed tomography) are made at baseline; subsequent cystoscopy and centrally read urine cytology are performed every 12 weeks through Year 2, every 24 weeks until end of Year 3, and in Year 4 and Year 5 in accordance with institutional standards of care. TURBT is conducted at 24 and 48 weeks. The primary end point for the 3 cohorts is overall CR rate at any time point. Secondary end points include duration of response (ie, from time of first CR achieved to first evidence of recurrence, progression, or death [whichever is earlier] for participants who achieve a CR), overall survival, PK immunogenicity of cetrelimab, safety and tolerability, and patient-reported outcomes. Exploratory end points include incidence and time to cystectomy (measured from randomization to date of cystectomy), biomarkers, and health care resource utilization. This study opened in January 2021 and is enrolling participants at ≈165 study sites worldwide. Currently, the study is active in 13 countries with 12 participants enrolled as of September 12, 2021. Clinical trial information: NCT04640623.

230 Background: Prostate specific antigen (PSA) screening remains a controversial issue. However, most urological guidelines recommend PSA testing through a shared decision-making process with the patient. The rate of PSA screening in men with a history of cancer compared to men with no cancer history is not well known. We aimed to compare PSA testing in men aged 55-69 years with and without a history of cancer (excluding prostate cancer patients). Methods: Utilizing the National Health Interview Survey (NHIS) a retrospective cross-sectional study between the years 2015 and 2018 was carried out to analyze and compare PSA testing rates in men aged 55-69 years. Multivariable logistic regression model was implemented do demonstrate potential associations with PSA testing. Results: A total of 13,850 men aged 55-69 years included in the NHIS Survey were analyzed. 1519 (10.9%) men had a history of cancer (non-prostate). On multivariable analysis, men who were previously diagnosed with cancer had a higher rate of PSA testing compared to men with no history of cancer (OR: 1.88, 95% CI 1.39-2.54, p < 0.001). Other factors associated with an increased likelihood of undergoing PSA testing included: age, homosexual orientation, and married men. In contrast, current smokers, American Indians and Alaskan Natives and Asians were less likely to undergo PSA testing. Conclusions: Our data suggest that men aged 55-69 with a history of cancer are more likely to undergo PSA testing than men with no cancer history.[Table: see text]

164 Background: Novel treatments for clinically advanced GUca including castrate resistant prostate ca (PC), bladder urothelial ca (BUC) and clear cell renal ca (ccRCC) are widely needed. Recently, the targeting of cancer cells with arginine accumulation caused by MTAP loss has emerged as a new synthetic lethality-based anti-cancer program. Methods: 8,436 mCRPC, 2,683 BUC and 841 ccRCC underwent hybrid-capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 tumor cell expression was determined by IHC (Dako 22C3). Results: 1.3% of PC, 24.2% of BUC and 5.5% of ccRCC featured MTAP loss. There were no significant age or gender differences associated with MTAP loss. CDKN2A/B loss ranged from 94% in ccRCC to > 99% in PC and BUC. The GA/tumor frequencies were similar when CDKN2A/B GA are excluded. In PC, GA in TP53, PTEN and BRCA1 were more frequent, while GA in AR, CDK12, RB1 and BRCA2 were less frequent in cases with MTAP loss. In BUC, GA in TSC1 and FGFR3 were more frequent and GA in RB1and TP53 were less frequent in cases with MTAP loss. In ccRCC, GA in NF2 were more frequent in cases with MTAP loss, while GA in VHL and PBRM1 were less frequent in cases with MTAP loss. “Targetable” kinase GA were rare in all groups, except for FGFR3 GA in MTAP loss BUC. Immunotherapy (IO) putative biomarkers varied among tumors, with MSI-high status less frequent and TMB ≥ 10 mut/Mb more frequent in BUC MTAP-intact than BUC with MTAP loss. PD-L1 expression was similar except for high PD-L1 expression more frequent in MTAP-intact BUC. Conclusions: When compared with PC and ccRCC, the clinical development of novel drugs, such as PRMT5 and MTA2 inhibitors in GUca will likely be focused on BUC given the 24% frequency of MTAP loss in that tumor type. CGP of PC, BUC and ccRCC reveal significant differences in GA in MTAP-intact and tumors with MTAP loss, which may impact future combinatorial clinical trial designs.[Table: see text]

563 Background: Immunohistochemistry (IHC) to determine PD-L1 expression level has been proposed a companion assay related to the approval of immune checkpoint inhibitors in UBC. We hypothesized that the GA profiles would differ between UBC featuring high vs negative PD-L1 expression. Methods: 102 cases of advanced UBC with known PD-L1 expression underwent hybrid-capture based comprehensive genomic profiling to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Tumor cell (TC) PD-L1 expression was determined by IHC (Dako 22C3). Only PD-L1 high (H) (≥50% TC expression) and negative (N) (0% TC expression) cases were included with PD-L1 Low (1-49% TC expression) cases excluded from this study. Results: Overall, only 2 (8.3%) of the 24 PD-L1H UBC featured CD274 ( PD-L1) amplification (mean 19 copies) and none of 78 PD-L1N had CD274 amp (P =.05). The gender, age was similar in the groups. When compared with the PD-L1H UBC cases, FGFR3 GA were significantly more frequent in the UBC PD-L1N cases (p =.02). Currently “untargetable” GA that were more frequent in the PD-L1H UBC, but did not reach statistical significance, included TP53, TERT and RB1. MTAP loss, a potential target for PRMT5 and MTA2 inhibitors, were 3X more frequent in the PD-L1N UBC. ERBB2 amplification and ERBB3 and PIK3CA short variant (SV) GA were more frequent in the PD-L1N UBC with differences not reaching significance. Other ICPI-associated potential biomarkers, including MSI status, TMB level and GA in PBRM1, STK11 and MDM2 were not significantly different in the groups. For UBC cases where a mutational signature could be determined, 10/12 (83%) of PD-L1H and 21/29 (72%) of PD-L1N UBC featured APOBEC signature; 2 PD-L1N featured MMR signature and 6 PD-L1N UBC featured no dominant signature. Conclusions: PD-L1H and PD-L1N subtypes of UBC differ in their genomic profiles:PD-L1N UBC features greater frequencies of potentially “targetable” GA, including FGFR3, ERBB2, ERBB3 and PIK3CA. PD-L1 IHC may thus not only play a role in the selection of ICPI for advanced UBC but also in designing trials that may combine ICPI with targeted therapies. Limitations include small sample size, possible selection bias and lack of clinical annotation.[Table: see text]

443 Background: Electronic cigarette smoking and similar novel smoking modalities have raised questions about their impact on various cancers compared with traditional forms of tobacco smoking. Tobacco smoking has been concretely proven to increase the risk of many cancers, including lung (LCa) and bladder (BCa) cancer. To date, there is little data on how e-cigarette smoking impacts the incidence of these cancers. We investigated whether any disparities exist in the prevalence of LCa and BCa between various smoking histories using a US nationally representative data source. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database between 2016-2018. Primary endpoint was self-reported occurrence of LCa and BCa diagnosis. Multivariable logistic regression analyses assessed possible association of various covariates with diagnosis of these cancers. Results: Prevalence of BCa and LCa was higher in all smoking histories compared to never smokers. Patients with a history of e-cigarette smoking vs. no history of e-cigarette smoking were significantly younger at BCa diagnosis (56.87 [±9.86] vs. 65.00 [±12.60] years, p=0.001). Multivariable logistic regression models showed that a history of cigarette smoking and e-cigarette smoking individually was associated with increased ORs of 2.476 (p≤0.001) and 1.577 (p≤0.001) for BCa diagnosis, respectively, and 4.589 (p≤0.001) and 1.614 (p=0.007) for LCa diagnosis, respectively. Conclusions: Compared to never smokers, history of e-cigarette smoking was associated with increased risk of LCa and BCa development and earlier BCa diagnosis. Additional studies are needed to better define the public health effects of these novel and unregulated products.

292 Background: FLCN is a tumor suppressor gene associated with cutaneous hair follicle development. FLCN germline mutations are linked to inherited chrRCC in the Birt-Hogg-Dube (BHD) syndrome. We queried whether clinically sporadic chrRCC featured FLCN mutations by comparing the genomic profiles of chrRCC with ccRCC. Methods: 108 chrRCC and 2110 ccRCC underwent hybrid-capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: Patients (pts) with chrRCC were more frequently female and younger than pts with ccRCC p

Patients with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk testicular cancer might receive either 4 cycles of etoposide and cisplatin (EP × 4) or 3 cycles of bleomycin, etoposide, and cisplatin (BEP × 3). We sought to examine differences in survival after retroperitoneal lymph node dissection (PC-RPLND) between patients who received EP × 4 compared with BEP × 3.The Indiana University Testis Cancer database was queried to identify IGCCCG good-risk PC-RPLND patients who received either EP × 4 or BEP × 3 induction chemotherapy. The primary outcome was overall survival (OS). Kaplan-Meier plots were generated for the EP × 4 and BEP × 3 groups and compared using the log rank test. Cox regression analysis was used to determine risk of mortality.A total of 223 patients met inclusion criteria between 1985 and 2011. Induction chemotherapy consisted of EP × 4 in 45 (20%) patients and BEP × 3 in 178 (80%). Most patients (78%) received their chemotherapy at outside institutions and were subsequently referred for PC-RPLND. The location of treating institution did not influence outcomes significantly when similar chemotherapy regimens were compared in this good-risk cohort. The 10-year OS for the EP × 4 and BEP × 3 groups were 91% and 98%, respectively (log rank P .01). The adjusted risk of death in the EP × 4 group showed a nonsignificant trend of 3 times greater compared with the BEP × 3 group (hazard ratio, 3.1; 95% confidence interval, 0.8-12.0; P = .10).The regimen of BEP × 3 resulted in a trend toward improved survival, however, this did not reach statistical significance. The location of treating institution seems less important in this risk group of patients.

Background Carcinoma of the urethra (UrthCa) is an uncommon Genitourinary (GU) malignancy that can progress to advanced metastatic disease. Methods One hundred twenty-seven metastatic UrthCa underwent hybrid capture-based comprehensive genomic profiling to evaluate all classes of genomic alterations (GA). Tumor mutational burden was determined on up to 1.1 Mbp of sequenced DNA, and microsatellite instability was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results Forty-nine (39%) urothelial (UrthUC), 31 (24%) squamous (UrthSCC), 24 (19%) adenocarcinomas NOS (UrthAC), and 12 (9%) clear cell (UrthCC) were evaluated. UrthUC and UrthSCC are more common in men; UrthAC and UrthCC are more common in women. Ages were similar in all 4 groups. GA in PIK3CA were the most frequent potentially targetable GA; mTOR pathway GA in PTEN were also identified. GA in other potentially targetable genes were also identified including ERBB2 (6% in UrthUC, 3% in UrthSCC, and 12% in UrthAC), FGFR1-3 (3% in UrthSCC), BRAF (3% in UrthAC), PTCH1 (8% in UrthCC), and MET (8% in UrthCC). Possibly reflecting their higher GA/tumor status, potential for immunotherapy benefit associated with higher tumor mutational burden and PD-L1 staining levels were seen in UrthUC and UrthSCC compared to UrthAC and UrthCC. Microsatellite instability high status was absent throughout. Conclusions Comprehensive genomic profiling reveals GA that may be predictive of both targeted and immunotherapy benefit in patients with advanced UrthCa and that could potentially be used in future adjuvant, neoadjuvant, and metastatic disease trials.

129 Background: Data on heterogeneity in cancer screening and diagnosis rates among lesbians/gays and bisexuals is lacking. Recent studies showed that lesbians/gays and bisexuals have decreased healthcare utilization compared to heterosexual counterparts and continue to experience discrimination in healthcare. Few studies have examined how sexual orientation impacts cancer screening and prevalence. We, therefore, investigated the association between sexual orientation and prevalent sex-specific cancer including prostate, breast, and cervical cancer. Methods: This was a cross-sectional survey-based US study, including men and women aged 18+ from the Health Information National Trends Survey (HINTS) database between 2017-2019. The primary endpoint was individual-reported prostate, breast, and cervical cancer screening and prevalence rates among heterosexual and LGB men and women. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. Results: Overall, 4,441 and 6,333 heterosexual men and women, respectively, were compared to 225 and 213 lesbian/gay and bisexual men and women, respectively. Lesbians/gays and bisexuals were younger and less likely to be screened for prostate, breast, and cervical cancer than heterosexuals. A higher proportion of heterosexual women than lesbian and bisexual women were screened for cervical cancer with pap smears (95.36% vs. 90.48% and 86.11%, p = < 0.001) and breast cancer with mammograms (80.74% vs. 63.81% and 45.37%, p = < 0.001). Similarly, a higher proportion of heterosexual men than gay and bisexual men were screened for prostate cancer with PSA blood tests (41.27% vs. 30.53% and 27.58%, p = < 0.001). Conclusions: Lesbians/gays and bisexuals in the US may be less likely to undergo screening of sex-specific prevalent malignancies, including prostate, breast, and cervical cancer. Healthcare professionals should be encouraged to improve cancer screening among lesbians/gays and bisexuals.

INTRODUCTION AND OBJECTIVE:We performed comprehensive genomic profiling (CGP) on separate cohorts of pre-systemic treatment (pre) PT and post-treatment (post) MET sites to uncover the similarities ...