Baseline Circulating Tumor Cells Count Research Articles

Abstract PO3-06-14: Phase I/II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer

Abstract Background: Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer (TNBC). This trial evaluated the efficacy of pembrolizumab in combination with binimetinib, a MEK inhibitor. Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy were enrolled. Treatment includes a 2-week run-in with binimetinib followed by pembrolizumab. There were 2 dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL -1. A standard 3+3 design was used in Phase I, and Simon’s two-stage Optimal design was used in Phase II. PD-L1 22C3 was performed in archival samples with CPS ≥ 10 considered as positive (PD-L1+). Tumor-infiltrating lymphocytes (TILs) were quantified into 0, 1, 2, and 3+. Circulating tumor cells (CTC) and circulating cancer-associated macrophage-like cells (CAML) were isolated using CellSieve microfilters and immunofluorescently labeled with PD-L1 and p-ERK. Wilcoxon rank sum test, Chi-square test, Cox regression model, and Spearman correlation were used for analysis. Results: 22 patients were enrolled with a median age of 58 years old. Dose-limiting toxicity (DLT) was observed in 2 out of 4 patients in DL 0, with grade 3 ALT abnormality, flank pain, and nausea. In the next 6 patients in DL -1, there was 1 DLT with grade 3 AST/ALT abnormality. There were 17 patients treated with DL -1 and were evaluable for response. The objective response rate (ORR) was 29.41% (95% CI: 10.31-55.9) with 1 complete response (CR) and 4 partial responses (PR). The clinical benefit rate (CBR ≥ 24 weeks) was 35.29% (95% CI: 14.21-61.67). ORR in patients without liver metastases was 55.56% (95% CI: 21.20 - 86.30) and CBR was 66.67% (95% CI: 29.93-92.51). No response was observed in all 5 patients with liver metastases. There were 40.9% of patients with PD-L1 CPS ≥ 10. ORR in patients with PD-L1+ was 80%. However, 11.1% of patients with PD-L1 negative tumors also had an objective response and 44.4% of patients had clinical benefit ≥ 24 weeks. PD-L1 expression in archival tissue was associated with ORR (p 0.032) but not CBR (p 0.198), progression-free survival (PFS, p 0.373), and overall survival (p 0.348). TILs in archival tissue were also not associated with CBR (p 0.155) and PFS (p 0.157). One patient with TILs 0 had a stable disease ≥ 24 weeks and 2 patients TILs 1+ also had an objective response. We further evaluated blood-based biomarkers with CTC and CAML. Baseline PD-L1 in CAML (p 0.04) and decline in CAML size (p 0.02) after 1 cycle was significantly associated with CBR. However, baseline CTC count, CAML count (p 0.64), CAML size (p 0.46), p-ERK in CAML (p 0.23), and changes in CTC count, CAML count (p 0.83), p-ERK (p 0.07), and PD-L1 (p 0.08) in CAML were not significantly associated with responses. Using Cox regression analysis, a reduction in CAML count (p 0.02), CAML size (p 0.01), and PD-L1 in CAML (p 0.03) were associated with significant improvement in overall survival but not the reduction in p-ERK (p 0.6). However, PD-L1 expression in CAML is not associated with PD-L1 expression in archival tissue (Spearman correlation 0.13). Conclusions: Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Consistent with the preclinical data that MEKi can restore T cell function, promising activity was observed even in patients with low TILs and PD-L1 negative, particularly in patients without liver metastases. PD-L1 expression in peripheral blood CAML rather than archival tumor tissue may serve as a better biomarker to predict the clinical benefit of this combination. Early reductions in CAML count and size, were also significantly associated with responses. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination. Citation Format: Saranya Chumsri, Joseph Larson, Daniel Adams, Kathleen Tenner, Cha-Mei Tang, Morgan Weidner, Amanda Arnold, Dana Haley, Pooja Advani, Kostandinos Sideras, Alvaro Moreno-Aspitia, Edith Perez, Keith Knutson. Phase I/II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-14.

Abstract PO1-16-02: Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC)

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC < 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were < 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p< 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P< 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (< 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs < 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-02.

Circulating tumor cells help differentiate benign ovarian lesions from cancer before surgery: A literature review and proof of concept study using flow cytometry with fluorescence imaging.

Current tools are insufficient for distinguishing patients with ovarian cancer from those with benign ovarian lesions before extensive surgery. The present study utilized a readily accessible platform employing a negative selection strategy, followed by flow cytometry, to enumerate circulating tumor cells (CTCs) in patients with ovarian cancer. These counts were compared with those from patients with benign ovarian lesions. CTC counts at baseline, before and after anticancer therapy, and across various clinical scenarios involving ovarian lesions were assessed. A negative-selection protocol we proposed was applied to patients with suspected ovarian cancer and prospectively utilized in those subsequently confirmed to have malignancy. The protocol was implemented before anticancer therapy and at months 3, 6, 9 and 12 post-treatment. A cut-off value for CTC number at 4.75 cells/ml was established to distinguish ovarian malignancy from benign lesions, with an area under the curve of 0.900 (P<0.001). In patients with ovarian cancer, multivariate Cox regression analysis revealed that baseline CTC counts and the decline in CTCs within the first three months post-therapy were significant predictors of prolonged progression-free survival. Additionally, baseline CTC counts independently prognosticated overall survival. CTC counts obtained with the proposed platform, used in the present study, suggest that pre-operative CTC testing may be able to differentiate between malignant and benign tumors. Moreover, CTC counts may indicate oncologic outcomes in patients with ovarian cancer who have undergone cancer therapies.

Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity. Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction. The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase. Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

Circulating tumor cells as a predictor and prognostic tool for metastatic clear cell renal carcinoma: An immunocytochemistry and genomic analysis

BackgroundTreatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors. ObjectiveWe evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC. Comparisons of CTC counts, protein expression profiling, and DNA mutants were made in relation to overall survival and progression-free survival. MethodsCTCs were isolated from 10 mL blood samples using the ISET® system (Isolation by SizE of Tumor Cells; Rarecells, France) and counted. Protein expression was evaluated in immunocytochemistry assays. DNA mutations were identified with next generation sequencing (NGS). ResultsBlood samples (10 mL) were collected from 12 patients with mccRCC before the start of first-line systemic therapy, and again 30 and 60 days after the start of treatment. All 12 patients had CTCs detected at baseline (median, 1.5 CTCs/mL; range: 0.25–7.75). Patients with CTC counts greater than the median had two or more metastatic sites and exhibited worse progression-free survival (19.7 months) compared to those with CTC counts less than the median (31.1 months). Disease progression was observed in 7/12 patients during the study. Five of these patients had baseline CTC counts greater than the median, one had higher CTC levels at the second blood collection, and one patient had CTCs present at 1 CTC/mL which positively stained for PD-L1, N-cadherin, VEGF, and SETD2. CTC DNA from six patients with worse outcomes was subjected to NGS. However, no conclusions could be made due to the low variant allele frequencies. ConclusionDetection of CTCs in patients with mccRCC receiving first-line treatment is a feasible tool with prognostic potential since increased numbers of CTCs were found to be associated with metastasis and disease progression.

Baseline circulating tumor cell (CTC) count as a prognostic marker of overall survival (OS) in metastatic hormone sensitive prostate cancer (mHSPC): Results from SWOG S1216, a phase III randomized trial of androgen deprivation plus orteronel (cyp17 inhibitor) or bicalutamide.

5080 Background: Biomarkers are needed to predict clinical outcomes in mHSPC. We previously reported that baseline CTC counts in S1216 were prognostic of PSA response and disease progression ( ASCO 2020; CCR 2021). However, the trial’s primary overall survival (OS) endpoint was not yet mature at that time. Here we present the final results of S1216 using all available samples to assess the prognostic value of CTC counts for response, progression, OS, and treatment arm interactions. Methods: In S1216, peripheral blood was drawn with informed consent at registration (baseline) and at progression to metastatic castrate resistant prostate cancer (mCRPC). CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini). CTC counts were evaluated for associations with 3 pre-specified trial endpoints: 7-month PSA (7mPSA) ≤ 0.2 ng/ml vs. 0.2–4.0 vs. &gt; 4.0 using a generalized logit model; and progression-free survival (PFS) and OS using Cox regression. Results: From 2014 to 2021, 503 evaluable samples were collected at baseline and 93 at progression. Baseline CTC count was ≥5 in 11.9% of samples, 1-4 in 19.3%, and 0 in 66.8%. Comparing men with 0 vs. ≥5 CTCs at baseline, those with 0 CTCs were significantly more likely to attain a complete PSA response and had significantly lower risk of a PFS event and death after adjusting for clinical covariates (disease burden, bone metastases, age, race, alkaline phosphatase, hemoglobin, PSA, treatment arm). These associations were not modified by treatment arm. Progression CTCs &lt;5 vs. ≥5 also were prognostic of OS (logrank p=0.001), consistent with prior findings in mCRPC. Same-patient CTC counts in matched baseline-progression pairs (n=61) were highly correlated (Spearman p&lt;0.001). Conclusions: CTC count at the start of treatment for mHSPC was highly prognostic of PSA response, PFS, and OS; associations that held in both treatment arms. Moreover, baseline CTC count strongly correlated with progression count, suggesting that mild vs. aggressive disease phenotypes may persist from mHSPC to mCRPC. This evidence from a large prospective phase 3 trial suggests that baseline CTC count is a valuable prognostic marker in men initiating therapy for mHSPC, discriminating those likely to experience favorable vs. unfavorable response and OS. [Table: see text]

Circulating tumor cells in patients with hormone receptor-positive, HER2-negative metastatic breast cancer receiving palbociclib with fulvestrant after progression on palbociclib with an aromatase inhibitor.

e13018 Background: High levels of circulating tumor cells (CTCs) at initiation of therapy in patients with metastatic breast cancer (MBC) are associated with worse prognosis. In patients with hormone receptor–positive (HR+), HER2-negative MBC, the benefit of maintaining CDK4/6 inhibitor (CDK4/6i) after progression on first-line therapy with endocrine therapy and CDK4/6i is not fully defined. To study the relationship between CTCs, tumor characteristics, and clinical outcomes, we enumerated CTC dynamics in patients with HR+ HER2- MBC enrolled on a phase II, multi-center, open-label interventional trial of palbociclib and fulvestrant after disease progression on prior palbociclib with an aromatase inhibitor (NCT02738866). Methods: Blood samples from study participants were collected at baseline (pretreatment), cycle 2 (C2, 8 weeks after initiation of fulvestrant and palbociclib), and at disease progression. Using a previously analytically validated assay (CellSearch), CTCs were enumerated. Progression-free survival (PFS) was estimated using the Kaplan Meier method. The relationship between CTC count at baseline (&lt; 5, &gt;5/7.5 ml Whole Blood (WB)) and PFS was analyzed using Cox proportional hazards regression. The association between PFS and CTC count among patients with baseline CTC ≥5 was estimated with a Cox proportional hazards model, adjusting for age, race, and progesterone receptor (PgR). Results: Between May 2017 and September 2022, baseline samples were collected from 52 of 60 trial participants enrolled at 5 centers in the United States, mean age 55 years (SD 14). Baseline CTC counts were &lt;5 in 30/52 (58%) and &gt;5 in 22/52 (42%) of participants. Among participants at baseline, only tissue PgR negativity was associated with higher likelihood of having elevated CTCs &gt;5 (p = 0.04). Association of CTCs &gt;5 and select patient and tumor characteristics is shown in Table 1. There was no statistically significant association between continuously measured CTC and PFS among those with elevated CTCs at baseline. Median duration of therapy among the entire 52 participant cohort was 4 months. Median PFS in participants with baseline CTC &lt;5 vs &gt;5/7.5 ml WB was 7.83 (95% CI [5.37, 12.60]) and 2.83 (95% CI [1.77, 4.73]) months, respectively (HR): 2.10, 95% CI [1.15, 3.82], p = 0.01). Conclusions: Baseline CTCs &gt;5/7.5 ml WB conferred a 2-fold increased risk of disease progression. Tissue PgR negativity was associated with baseline CTCs &gt;5. These data can be used to inform new studies in which baseline and early change in CTCs may inform second line treatment decisions in women with HR+, HER2- MBC. [Table: see text]

Circulating tumor cell abundance in head and neck squamous cell carcinoma decreases with successful chemoradiation and cetuximab treatment

Head and neck squamous cell carcinoma (HNSCC) is a common and deadly cancer. Circulating tumor cell (CTC) abundance may a valuable, prognostic biomarker in low- and intermediate-risk patients. However, few technologies have demonstrated success in detecting CTCs in these populations. We prospectively collected longitudinal CTC counts from two cohorts of patients receiving treatments at our institution using a highly sensitive device that purifies CTCs using biomimetic cell rolling and dendrimer-conjugated antibodies. In patients with intermediate risk human papillomavirus (HPV)-positive HNSCC, elevated CTC counts were detected in 13 of 14 subjects at screening with a median of 17 CTC/ml (range 0.2–2986.5). A second cohort of non-metastatic, HPV- HNSCC subjects received cetuximab monotherapy followed by surgical resection. In this cohort, all subjects had elevated baseline CTC counts median of 73 CTC/ml (range 5.4–332.9) with statistically significant declines during treatment. Interestingly, two patients with recurrent disease had elevated CTC counts during and following treatment, which also correlated with growth of size and ki67 expression in the primary tumor. The results suggest that our device may be a valuable tool for evaluating the success of less intensive treatment regimens.

Abstract 5454: Peripheral blood biomarkers in Phase II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer

Abstract Background: Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer (TNBC). This trial evaluated the efficacy of pembrolizumab and MEK inhibitor, binimetinib. Here we evaluated potential biomarkers in peripheral blood to predict response. Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy were enrolled. Treatment includes a 2-week run-in with binimetinib followed by pembrolizumab. There were 2 dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL -1. A standard 3+3 design was used in phase I, and Simon’s two-stage Optimal design was used in phase II. Circulating tumor cells (CTC) and circulating cancer-associated macrophage-like cells (CAML) were isolated using CellSieve microfilters and immunofluorescently labeled with PD-L1 and p-ERK. Wilcoxon rank sum test and Cox regression model were used for analysis. Results: A total of 22 patients were enrolled, with a median age of 58 years old. Dose-limiting toxicity (DLT) was observed in 2 out of 4 patients in DL 0, with grade 3 ALT abnormality, flank pain, and nausea. In the next 6 patients in DL -1, there was 1 DLT with grade 3 AST/ALT abnormality. There were 17 patients treated with DL -1 and were evaluable for response. The objective response rate (ORR) was 29.41% (95% CI: 10.31-55.9) with 1 complete response (CR) and 4 partial responses (PR). The clinical benefit rate (CBR ≥ 24 weeks) was 35.29% (95% CI: 14.21-61.67). ORR in patients without liver metastases was 55.56% (95% CI: 21.20 - 86.30), and CBR was 66.67% (95% CI: 29.93-92.51). There was no response observed in all 5 patients with liver metastases. Baseline mean CTC count was 1.3 cells, and CAML count was 8.9 cells/7.5 mL. Baseline PD-L1 in CAML (p 0.04) and decline in CAML size (p 0.02) after 1 cycle were significantly associated with CBR. However, baseline CTC count, CAML count (p 0.64), CAML size (p 0.46), p-ERK in CAML (p 0.23), and changes in CTC count, CAML count (p 0.83), p-ERK (p 0.07), and PD-L1 (p 0.08) in CAML were not significantly associated with responses. Using Cox regression analysis, a reduction in CAML count (p 0.02), CAML size (p 0.01), and PD-L1 in CAML (p 0.03) were associated with significant improvement in overall survival but not the reduction in p-ERK (p 0.6). Conclusions: Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Promising activity was observed in patients without liver metastases. Baseline PD-L1 expression, early reduction in CAML count, size, and PD-L1 expression were significantly associated with subsequent responses, providing potential noninvasive biomarkers to predict response to this combination. Future larger clinical trials are warranted to further evaluate the efficacy of this combination. Citation Format: Saranya Chumsri, Joseph J. Larson, Daniel L. Adams, Kathleen S. Tenner, Cha-Mei Tang, Morgan T. Weidner, Amanda N. Arnold, Dana L. Haley, Pooja Advani, Kostandinos Sideras, Alvaro Moreno-aspitia, Edith A. Perez, Keith L. Knutson. Peripheral blood biomarkers in Phase II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5454.

MP29-10 PROGNOSTIC VALUE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO (NLR) IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) RECEIVING PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED RADIONUCLIDE THERAPY (TRT)

You have accessJournal of UrologyCME1 Apr 2023MP29-10 PROGNOSTIC VALUE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO (NLR) IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) RECEIVING PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED RADIONUCLIDE THERAPY (TRT) Judith Stangl-Kremser, Michael Sun, Benedict Ho, Joseph Thomas, Jones Nauseef, Joseph Osborne, Ana Molina, Cora Sternberg, David Nanus, Neil Bander, and Scott Tagawa Judith Stangl-KremserJudith Stangl-Kremser More articles by this author , Michael SunMichael Sun More articles by this author , Benedict HoBenedict Ho More articles by this author , Joseph ThomasJoseph Thomas More articles by this author , Jones NauseefJones Nauseef More articles by this author , Joseph OsborneJoseph Osborne More articles by this author , Ana MolinaAna Molina More articles by this author , Cora SternbergCora Sternberg More articles by this author , David NanusDavid Nanus More articles by this author , Neil BanderNeil Bander More articles by this author , and Scott TagawaScott Tagawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA TRT is a promising therapy for patients with mCRPC. Known prognostic factors for mCRPC include CALGB (Halabi) risk group and baseline circulating tumor cell (CTC) count. Here, we report associations between NLR and PSA response and overall survival (OS) in men with mCRPC treated on sequential prospective clinical trials at a single institution. METHODS: Patients treated on prospective studies from 2000 to 2021 were included in this analysis. Variables assessed: baseline neutrophil count:lymphocyte count ratio, baseline CTC count (CellSearch, favorable vs unfavorable), CALGB risk group, and administered radioactivity level. We used a Cox proportional hazards model to investigate the association between NLR and OS and logistic regression to determine the association between NLR and >50% PSA decline (PSA50). RESULTS: 180 patients were included in this analysis. Median age 71 (IQR 66-77.5), PSA 57.3 ng/mL (21.3-294.9), 80 (44.4%) prior chemotherapy, 86 (47.7%) prior abiraterone or androgen receptor signaling inhibitor, 167 (92.8%) bone metastases, 141 (78.3%) nodal metastases, 113 (62.8%) CALGB high-risk group. 94 (52.2%) received 177Lu-J591, 51 (28.3%) 177Lu-PSMA-617, 28 (15.6%) 225Ac-J591, 7 (3.9%) 90Y-J591. Median ANC 4.1 (IQR 3.1-5.1), ALC 1 (0.75-1.5), NLR 3.75 (2.63-5.92). On univariate analysis, higher NLR was associated with worse OS (HR 1.06, 95%CI 1.02-1.09, p=0.002) and trended toward lower rates of PSA50 (HR 1.08; 95% CI 0.99-1.17, p=0.067). On multivariable analysis, after controlling for CTC count and CALGB risk group, the relationship between higher NLR and worse OS persisted (HR 1.05; 95% CI 1.003-1.11, p=0.036). Stratifying patients by low vs high NLR (relative to median NLR), patients with low NLR had longer OS (23.7 vs 15 months, p=0.024). CONCLUSIONS: For patients with mCRPC receiving PSMA TRT, NLR may have prognostic implications with higher NLR associating with lower likelihood of PSA response and shorter overall survival. Source of Funding: NIH, Department of Defense, Weill Cornell Medicine, Prostate Cancer Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e384 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Judith Stangl-Kremser More articles by this author Michael Sun More articles by this author Benedict Ho More articles by this author Joseph Thomas More articles by this author Jones Nauseef More articles by this author Joseph Osborne More articles by this author Ana Molina More articles by this author Cora Sternberg More articles by this author David Nanus More articles by this author Neil Bander More articles by this author Scott Tagawa More articles by this author Expand All Advertisement PDF downloadLoading ...

Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56-74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.

Abstract GS3-09: GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial

Abstract Background: High circulating tumor cell (CTC) count (CTChigh) is a strong adverse prognostic factor in patients with metastatic breast cancer (mBC). In the STIC CTC trial (NCT01710605), run before the introduction of CDK4/6 inhibitors for ER+/HER2- mBC, we showed that CTC count (CTC arm) was non inferior to clinician’s choice (standard arm) on progression-free survival (PFS) to guide first line treatment selection between chemotherapy (CT) and endocrine therapy (ET) (Bidard et al., JAMA Oncol 2021). Of note, patients who had treatment escalated from ET (a priori clinician choice) to CT in the CTC arm, had a significantly longer PFS. We report here overall survival (OS) results of this multicenter CTC clinical utility trial. Methods: In the CTC arm, N=377 patients had their treatment determined by baseline CTC count: CT if CTChigh (≥5 CTCs/7.5 mL, CellSearch®), ET if CTClow. In the standard arm (N=378 patients), the choice was left to the investigator: CT if clinical high risk (Clinhigh), ET if clinical low risk (Clinlow). Therefore, patients with discordant Clinlow/CTChigh or Clinhigh/CTClow profiles had their first line treatment escalated from ET (standard arm) to CT (CTC arm) or de-escalated from CT (standard arm) to ET (CTC arm), respectively. Patients with concordant Clinlow/CTClow and Clinhigh/CTChigh profiles received ET and CT in both arms, respectively. Results: Among 755 randomized patients, N=189 (25.0%) had a Clinlow/CTChigh profile, N=103 (13.6%) Clinhigh/CTClow, N=363 (48.2%) Clinlow/CTClow and N=100 (13.2%) Clinhigh/CTChigh. OS was analyzed after a median follow-up of 57 months and 382 events (50.6%). In the Clinlow/CTChigh subgroup, CT in the CTC arm led a longer OS (mOS: 51.8 months [43.3-NR]) than ET in the standard arm (35.4 months [30.4-45.4]; HR=0.53 [0.36-0.78], p=0.001). In patients Clinhigh/CTClow, no significant difference was observed whether they received CT (standard arm) or ET (CTC arm) (45.9 months [36.3-59.8] vs 49.4 months [35.4-65.4]; HR=0.88 [0.51-1.51], p=0.63). Pooling the two discordant groups (Clinlow/CTChigh or Clinhigh/CTClow), the CTC-driven strategy was superior to the clinician-driven treatment decision (HR=0.63 [0.46-0.86], p=0.02). Pooling all concordant and discordant groups together, a median OS of 45.5 (95%CI=[40.9-51.1]) and 51.3 months [46.8-55.1] was observed in the standard and CTC arms, respectively (HR=0.84 [0.69-1.03], p=0.10). Conclusions: Prognostic information brought by CTC or standard factors is discordant in 40% of patients with ER+ HER2- mBC. In case of a discordant estimate, the STIC CTC trial shows the superiority on OS of the CTC-driven treatment decision strategy. These results also suggest a possible clinical utility of CTC to adjust systemic treatment for mBC in second and later lines, after progression on CDK4/6 inhibitors. Funding:The study was funded by Institut Curie; the French National Cancer Institute (INCa), as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011 (STIC 2011); and Menarini Silicon Biosystems (Castel Maggiore, Italy). Citation Format: Francois-Clement Bidard, Nicolas Kiavue, Catherine Alix-Panabières, Sylvain Dureau, Thomas Bachelot, Hugues Bourgeois, Anthony Gonçalves, Etienne Brain, Sylvain Ladoire, Florence Dalenc, Joseph Gligorov, Luis Teixeira, George Emile, Jean-Marc Ferrero, Delphine Loirat, Luc Cabel, Véronique Diéras, Frédérique Berger, William Jacot, Jean-Yves Pierga. GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-09.

The Role of Circulating Tumor Cells as Potential Predictive and Prognostic Factors in Cervical Cancers

<h3>Purpose/Objective(s)</h3> Circulating tumor cells (CTCs) are emerging biomarkers that may serve as both predictive and prognostic factors to improve the evaluation of cancer patients at risk of recurrence and metastatic spread. While the role of CTCs in gynecologic cancers remains incompletely understood, we know that CTCs have been demonstrated as a prognostic marker in other cancer types, with baseline CTC count appearing to be a strong predictor of outcomes. The aim of this study is to evaluate the potential role of CTCs as a non-invasive method to quantify a patient's risk of both recurrence and death following definitive chemoradiation for locally advanced gynecologic cancers. <h3>Materials/Methods</h3> 23 patients with non-metastatic cervical cancer (CC) receiving definitive radiation +/- chemotherapy were enrolled on a prospective single-arm clinical trial at our institution from 2018-2021. On trial, 4 - 5 blood samples were collected at baseline prior to receiving treatment, mid-treatment, end of treatment, and at 1- and 3-month follow-up. Samples were analyzed utilizing a novel liquid biopsy imaging system, the Axon Dx nCyte® System that allows for detection of CTCs and Hybrid Cells (HC) at very low concentrations with high specificity. HCs are defined as those similar in appearance to CTCs but with white cell expression, suggesting immune response at the site of the CTCs. Patient demographics and clinical outcomes including recurrence patterns were also recorded. <h3>Results</h3> Of the 23 CC patients, 17 (73.9%) had squamous cell carcinoma, 5 (21.7%) adenocarcinoma, and 1 (4.3%) small cell carcinoma. There were 2 (8.7%) patients with stage I disease, 9 (39.1%) stage II, 11 (47.8%) stage III, and 1 (4.3%) stage IV. CTCs were positive (+) in 12 (52.1%) patients, of which 6 (50%) had a recurrence, 5 (41.6%) of whom are deceased secondary to CC. The remaining 6 patients are alive without recurrence at this date, with only 1 having at least 12 months of follow up. HCs were present in 21 (91.3%) of the CC patients, including 11/12 of the CTC+ cases (CTC+HC+); however, they were also identified in another 9 patients as CTC-HC+. Of these CTC-HC+ patients, 4 (44%) have had a recurrence, 2 (22%) of whom are deceased secondary to CC. The remaining 5 are alive without recurrence at this date, with only one having less than 12 months of follow up. There have been no recurrences in the CTC-HC- subset of patients. <h3>Conclusion</h3> We have demonstrated that it is feasible to detect CTCs and HCs in a prospective cohort of patients with locally advanced CC utilizing Axon Dx's nCyte® System. In this single institution experience, the presence of CTCs/HCs correlates with worsened survival amongst women with locally advanced CC, perhaps indicating a prognostic biomarker of potential significant value in this patient population. Longer follow up and additional studies are indicated to further explore the significance of CTC/HC values, trends, and timing on patients' outcomes.

Prospective Evaluation of a Circulating Tumor Cell Sensitivity Profile to Predict Response to Cisplatin Chemotherapy in Metastatic Breast Cancer Patients.

BackgroundCisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.MethodsBased on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A’Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m2 cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS).ResultsThe best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) vs. 2.1 months [(95%CI 1.34-2.80)(p=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) vs. 5.6 months [(95%CI 3.60-7.64)(p=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors.ConclusionsThe CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients.Clinical Trial Registration(https://www.trialregister.nl/trial/3885, identifier NTR4046)

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p=.002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p=.003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Sensitive and dynamic CTCs measurement for prediction and monitoring of PD-1 therapy in GC/EGJC patients: Results from a pilot phase 2 study.

e16094 Background: Programmed death-ligand 1 (PD-L1) expression is currently being explored as a predictive biomarker for anti-PD-1antibody treatment in patients with advanced gastric or esophagogastric junction cancer (GC/EGJC) patients. Circulating tumor cells (CTCs) can be collected non-invasively and sequentially, and may allow real-time monitoring of immune activation in tumor. The aim of this study was to investigate whether PD-L1 expression on CTCs can accurately represent tumor PD-L1 expression and the potential of CTCs as a companion diagnosis (CDx) biomarker. Methods: We evaluated the CTCs counts and PD-L1 status on CTCs during treatment in a phase 2 clinical trial, where patients with previously treated gastric cancer received JS001 in combination with Apatinib. The multi-center trial was registered with ClinicalTrials.gov, number NCT04190745. Blood samples were collected from patients. Sixteen patients with GC were analyzed to investigate the association between clinical outcome and changes of CTC counts pre and post JS001 plus Apatinib. The correlation between the binary clinical outcome (SD/PR/CR vs. PD) and the change in CTCs counts pre and post treatment was analyzed using a logistic regression adjusting for baseline CTCs counts. PD-L1 expression on CTCs were analyzed to determine whether they were in accordance with tissue biopsy. Results: CTCs were detected in all the patients (16/16，100%) ranging from 1 to 33 CTCs/ml. PD-L1+ CTCs were detected in 12 of 16 patients (75%) ranging from 1 to 5 PD-L1 + CTCs/ml. PD-L1 expression in tumor tissue was positive in 11 of 13 patients (84.6%, positive means CPS &gt; = 1), the sensitivity of PD-L1+ CTCs is 90.9% (10/11) if using biopsy as gold standard. The only false negative patient though with CPS 40%, got no benefit from immunotherapy. The specificity of PD-L1+ CTCs detection is 100%, and the accuracy is 90.9%. Overall response rate of this regimen is 26.6% (4/15). Disease control rate is 53.3% (8/15). Progression free survival (PFS) was 2.43 months in all the evaluable patients. However, patients with PD-L1+ CTCs had a longer PFS compared to patients without PD-L1+ CTC (3.30months vs 1.37months, p = 0.001). Overall Survival is not reached. Change of CTCs counts after treatment was significantly correlated with clinical response (p = 0.024). The logistic model McFadden goodness of fit score was 0.435, which is a strong correlation value. Notably, one of the patients who had pseudo-progression shows remarked decreased CTCs count. Conclusions: Our results reveal the potential of CTCs as a noninvasive CDx biomarker in patients with advanced GC/EGJC.

Value of Early Circulating Tumor Cells Dynamics to Estimate Docetaxel Benefit in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients.

Simple SummaryThe prognostic role of CTC enumeration in mCRPC patients has been established in several studies, demonstrating a higher prognostic performance than post-treatment changes in PSA levels in patients treated with AR signaling inhibitors, but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. The results of this study showed a greater ability of early changes in circulating tumor cells (CTCs) compared to PSA response endpoints to predict overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel. These results encourage the clinical usefulness of CTC enumeration to determine the outcome of mCRPC patients.Circulating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3–6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3–6 weeks (CTC conversion (from ≥5 to <5 CTCs), CTC30 (≥30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.

Assessment of the Circulating Tumor Cells and Microsatellite Instability in Colorectal Cancer Patients: Prognostic and Diagnostic Value.

BackgroundMicrosatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients.MethodsCTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates.ResultsMSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (<4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P<0.001), decreased CTC levels during the course of treatment (P<0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P<0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P<0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P<0.001, P= 0.047, P=0.001 and P<0.001; respectively).ConclusionMSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients’ survival rates and outcomes.

Baseline and post-treatment circulating tumor cell (CTC) counts with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) in men with metastatic castration-resistant prostate cancer (mCRPC).

158 Background: CTC counts are an independent prognostic factor in men with mCRPC; certain changes following treatment (conversion from detectable to undetectable or unfavorable to favorable) are associated with improved overall survival. Most PSMA-TRT efficacy data have focused on PSA or imaging changes. Here, we describe baseline and post-treatment CTC counts from subjects receiving PSMA-TRT. Methods: Men with mCRPC treated on prospective clinical trials of PSMA-TRT and with available CTC counts (CellSearch) were included in our analysis. Depending upon the era of the trial, post-treatment counts were performed at 4-6 (initial era) or 12 weeks (recent era) after a single cycle of PSMA-TRT (individual trial data reported elsewhere). We describe CTC counts at baseline and compare pre-treatment counts to those after PSMA-TRT. Results: 116 men treated with PSMA-TRT had baseline CTC count (90 with both pre- and post-treatment CTC). Forty-four patients (37.9%) received 177Lu-J951, 46 (39.7%) received 177Lu-PSMA-617, and 26 (22.4%) received 225Ac-J591. Median age was 71.5. Fifty-eight patients (50%) had previously received taxane chemotherapy, median PSA was 82.98 ng/mL, and 66 (56.9%) were in the high-risk Halabi (CALGB) prognostic group. Eighty-nine out of one hundred sixteen (76.7%) had detectable baseline CTC and 58/116 (50%) had unfavorable baseline CTC count. Forty-nine out of seventy (70%) had post-treatment CTC count decline, 23/70 (32.9%) converted from detectable to undetectable, and 17/47 (36.2%) converted from unfavorable to favorable. CTC changes stratified by type of PSMA-TRT are reported in the table. Conclusions: This is the largest analysis of CTC changes in patients who have received PSMA-TRT. In addition to PSA changes and other previously reported outcomes, even when low doses of radionuclide therapy as part of dose-escalation studies are included, the majority with detectable CTC counts have post-treatment CTC count decline. A significant portion of patients experience favorable CTC changes. [Table: see text]

Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p &lt; 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p &lt; 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]