Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings.

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined. RESULTS: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65. CONCLUSIONS: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.

Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena.

Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors (i.e., International Society of Urological Pathology (ISUP) Grade Group 2)-twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study.

BACKGROUND: The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately. OBJECTIVE: To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa. DESIGN, SETTING, AND PARTICIPANTS: We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used. RESULTS AND LIMITATIONS: A total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8-24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT-positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET. CONCLUSIONS: PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa. PATIENT SUMMARY: We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.

The Evolving Role of Prostate-Specific Membrane Antigen-Based Diagnostics and Therapeutics in Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, 68Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from 177Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.

Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.