Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer

Nagaya, Naoya; Nagata, Masayoshi; Lü, Yan; Kanayama, Mayuko; Hou, Qi; Hotta, Zen-U; China, Toshiyuki; Kitamura, Kosuke; Matsushita, Kazuhito; Isotani, Shuji; Muto, Satoru; Sakamoto, Yoshiro; Horie, Shigeo

doi:10.1371/journal.pone.0226219

Cited by 33 publications

(29 citation statements)

References 31 publications

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“…Data obtained from other neoplastic diseases show conflicting information on a possible association between tumoral PSMA expression and survival: Whereas in primary lung tumors such as non-small cell lung cancer, PSMA expression and outcome seem not to be correlated (48,49), PSMA expression has shown to be a prognostic marker also in castration-resistant prostate cancer, adrenocortical tumors, or hepatocellular carcinoma. In those tumors, high PSMA expression correlates with a similarly poor prognosis in analogy to our data for glioblastoma patients in the present study (50)(51)(52). Interestingly, the change of the level of vascular PSMA expression between initial diagnosis and recurrence seems to be prognostic as well in glioblastoma: Patients with a strongly decreasing vascular PSMA expression survived longer than those with increasing vascular PSMA expression (22 months vs. 12 months post recurrence survival, see Figure 4B), which is especially interesting with regard to potential repeated non-invasive PSMA PET imaging over the disease course.…”

Section: Discussionsupporting

confidence: 88%

PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging

et al. 2021

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AimThe aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology.MethodsPatients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters.ResultsPSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index.ConclusionPSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients.

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Section: Discussionsupporting

confidence: 88%

PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging

et al. 2021

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“…High expression of PSMA in primary and metastatic tumor biopsies and in circulating tumor cells from patients with mCRPC has been associated with worse OS compared to low or absent PSMA expression, in recent studies ( 7 , 20 , 21 ). Besides this association between PSMA and a more aggressive biological behavior, the presence and amount of PSMA avid lesions may reflect the overall burden of disease (i.e., a larger volume lesion with the same cellular expression of PSMA may result in higher imaging uptake).…”

Section: Discussionmentioning

confidence: 95%

Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

et al. 2021

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BackgroundProstate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC).MethodsPatients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0–4 in order to determine an imaging score (IS). The IS (high: 2–4 versus low: 0–1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox’s proportional hazards models.ResultsHigh PSMA expression (IS 2–4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9–19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0–18.1) months compared to those with low expression [22.7 (95%CI: 17.7–30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p<0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2–2.2); p = 0.003].ConclusionPresence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes.

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“… Platelet-lymphocyte ratio (PLR) High pretreatment PLR associated with worse PFS, CSS, and OS [96] PLR may prove useful in risk classification [96] ; is quick, easy, and cheap to test; and deserves competition with other biomarkers in future studies. Prostate-specific membrane antigen (PSMA) and PSMA-PET-CT Expression of PSMA in CTCs associated with worse PSA progression-free survival, treatment response, and OS in CRPC patients [98] PSMA-PET-CT scanning is more accurate than the conventional method of CT + bone scan for detecting metastases [99] . Its overall value should be determined by comparison with other biomarkers.…”

Section: Resultsmentioning

confidence: 99%

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine

Jasu

Tolonen

Antonarakis

et al. 2021

European Urology Open Science

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Background Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design, setting, and participants We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of “skeletal-related events” complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. Conclusions The study identified novel outcome subgroups for future validation and provides “vision for mPC precision oncology 2020–2050” draft recommendations for future data collection and biomarker studies. Patient summary To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudi...

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Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer

Cited by 33 publications

References 31 publications

PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging

PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging

Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine

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