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Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer.

ABSTRACT: PURPOSE:Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis. METHODS:Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort. RESULTS:The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05). CONCLUSION:Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.

SUBMITTER: Salami SS

PROVIDER: S-EPMC7446477 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer.

Salami Simpa S SS Kaplan Jeremy B JB Nallandhighal Srinivas S Takhar Mandeep M Tosoian Jeffrey J JJ Lee Matthew M Yoon Junhee J Hovelson Daniel H DH Plouffe Komal R KR Kaffenberger Samuel D SD Schaeffer Edward M EM Karnes R Jeffrey RJ Lotan Tamara L TL Morgan Todd M TM George Arvin K AK Montgomery Jeffrey S JS Davenport Matthew S MS You Sungyong S Tomlins Scott A SA Curci Nicole E NE Kim Hyung L HL Spratt Daniel E DE Udager Aaron M AM Palapattu Ganesh S GS

JCO precision oncology 20190612

<h4>Purpose</h4>Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis.<h4>Methods</h4>Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both ...[more]

PMID: 32914029

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Project description:BackgroundUp to half of all men who undergo primary radiotherapy for localized prostate cancer (PCa) experience local recurrence.ObjectiveTo evaluate the safety and early functional and oncological outcomes of salvage magnetic resonance imaging-guided transurethral ultrasound ablation (sTULSA) for men with localized radiorecurrent PCa.Design setting and participantsThis prospective, single-center phase 1 study (NCT03350529) enrolled men with biopsy-proven localized PCa recurrence after radiotherapy. Multiparametric magnetic resonance imaging (mpMRI) and 18F prostate-specific membrane antigen-1007 (18F PSMA-1007) positron emission tomography (PET)-computed tomography (CT) were used to confirm organ-confined disease localization. Patients underwent either whole-gland or partial sTULSA, depending on their individual tumor characteristics.Outcome measurements and statistical analysisPatients were followed at 3-mo intervals. Adverse events (AEs, Clavien-Dindo scale), functional status questionnaires (Expanded Prostate Cancer Index [EPIC]-26, International Prostate Symptom Score, International Index of Erectile Function-5), uroflowmetry, and prostate-specific antigen (PSA) were assessed at every visit. Disease control was assessed at 1 yr using mpMRI and 18F-PSMA-1007 PET-CT, followed by prostate biopsies.Results and limitationsEleven patients (median age 69 yr, interquartile range [IQR] 68-74) underwent sTULSA (3 whole-gland, 8 partial sTULSA) and have completed 12-mo follow-up. Median PSA was 7.6 ng/ml (IQR 4.9-10) and the median time from initial PCa diagnosis to sTULSA was 11 yr (IQR 9.5-13). One grade 3 and three grade 2 AEs were reported, related to urinary retention and infection. Patients reported a modest degradation in functional status, most significantly a 20% decline in the EPIC-26 irritative/obstructive domain at 12 mo. A decline in maximum flow rate (24%) was also observed. At 1 yr, 10/11 patients were free of any PCa in the targeted ablation zone, with two out-of-field recurrences. Limitations include the nonrandomized design, limited sample size, and short-term oncological outcomes.ConclusionssTULSA appears to be safe and feasible for ablation of radiorecurrent PCa, offering encouraging preliminary oncological control.Patient summaryWe present safety and 1-yr functional and oncological outcomes of magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) as a salvage treatment for local prostate cancer recurrence after primary radiation. Salvage TULSA is safe and shows the ability to effectively ablate prostate cancer recurrence, with acceptable toxicity.

Project description:In radiotherapy (RT) of prostate cancer, dose escalation has been shown to reduce biochemical failure. Dose escalation only to determinate prostate tumor habitats has the potential to improve tumor control with less toxicity than when the entire prostate is dose escalated. Other issues in the treatment of the RT patient include the choice of the RT technique (hypo- or standard fractionation) and the use and length of concurrent/adjuvant androgen deprivation therapy (ADT). Up to 50% of high-risk men demonstrate biochemical failure suggesting that additional strategies for defining and treating patients based on improved risk stratification are required. The use of multiparametric MRI (mpMRI) is rapidly gaining momentum in the management of prostate cancer because of its improved diagnostic potential and its ability to combine functional and anatomical information. Currently, the Prostate Imaging, Reporting and Diagnosis System (PIRADS) is the standard of care for region of interest (ROI) identification and risk classification. However, PIRADS was not designed for 3D tumor volume delineation; there is a large degree of subjectivity and PIRADS does not accurately and reproducibly elucidate inter- and intra-lesional spatial heterogeneity. "Radiomics", as it refers to the extraction and analysis of large number of advanced quantitative radiological features from medical images using high throughput methods, is perfectly suited as an engine to effectively sift through the multiple series of prostate mpMRI sequences and quantify regions of interest. The radiomic efforts can be summarized in two main areas: (I) detection/segmentation of the suspicious lesion; and (II) assessment of the aggressiveness of prostate cancer. As related to RT, the goal of the latter is in particular to identify patients at high risk for metastatic disease; and the aim of the former is to identify and segment cancerous lesions and thus provide targets for radiation boost. The article is structured as follows: first, we describe the radiomic approach; and second, we discuss the radiomic pipeline as tailored for RT of prostate cancer. In this process we summarize the current efforts and progress in integrating mpMRI radiomics into the radiotherapeutic management of prostate cancer with emphasis placed on its role in treatment target definition, treatment plan strategizing, and prognostic assessment. The described concepts, methods and tools are not currently applicable to the radiation oncology practice outside of the research setting. More data are required in the form of clinical trials to assess the robustness of radiomics-based predictive models, and to maximize the efficacy of these models.

Project description:Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Dataset Information

Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer.

Publications

Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer.

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