Detection of Clinically Significant Prostate Cancer With 18F-DCFPyL PET/MR

Titre officiel

Detection of Clinically Significant Prostate Cancer With 18F-DCFPyL PET/MR

Sommaire:

Contexte :

À l’heure actuelle, les patients soupçonnés d’être atteints d’un cancer de la prostate subissent une biopsie systématique de la prostate guidée par échographie. Toutefois, près du quart des tumeurs significatives sur le plan clinique qui peuvent compromettre le bien-être d’un patient peuvent passer inaperçues lors d’une biopsie aléatoire. Si l’IRM permet de déceler davantage de tumeurs chez cette population de patients, son exactitude est limitée.

Hypothèse de l’étude :

Nous formulons l’hypothèse que l’examen hybride par TEP/IRM, un nouvel examen de dépistage intégrant l’IRM et l’imagerie moléculaire, améliorera le taux de dépistage des tumeurs significatives sur le plan clinique.

Méthodologie de l’étude :

Dans le cadre de cette étude prospective, nous recruterons 57 hommes soupçonnés d’être atteints d’un cancer de la prostate, mais ayant obtenu un résultat négatif après une biopsie systématique, qui ont reçu un diagnostic de maladie à faible risque, mais présentent des signes cliniques d’une tumeur plus agressive ou chez qui une tumeur localisée a été décelée et qui sont des candidats pour une ablation tumorale minimalement effractive (destruction de la tumeur au laser ou à l’aide d’ondes ultrasonores) chez qui il est crucial d’exclure d’autres sites tumoraux.

Tous les patients subiront un examen par TEP/IRM après l’injection d’un produit radiopharmaceutique appelé « 18F-DCFPyL ». Il s’agit d’un produit de dépistage radioactif qui s’est avéré sensible et spécifique au dépistage du cancer de la prostate lors d’études préliminaires.

Toutes les lésions décelées par TEP/IRM feront l’objet d’une biopsie guidée par échographie à l’aide des images de TEP/d’IRM fusionnées et d’échographie, puis elles seront comparées à l’histopathologie. La mesure du critère d’évaluation principal de cette étude est la proportion de cancers de la prostate significatifs sur le plan clinique qui sont décelés par TEP/IRM, comparativement à l’IRM seule. Le dépistage amélioré du cancer de la prostate significatif sur le plan clinique pourrait permettre d’élaborer une approche thérapeutique ciblée et personnalisée, de diminuer la morbidité et d’améliorer éventuellement les résultats pour les patients dans l’ensemble.

Description de l'essai

Primary Outcome:

  • Rate of clinically significant prostate cancer (csPCa) detected in the study population by 18F-DCFPyL-PET/mpMR as compared to mpMR alone
Secondary Outcome:
  • Change in eligibility for focal therapy according to each modality
  • Correlation of tumour grade to PSMA expression on PET (SUV).
Prostate cancer overview: Prostate cancer (PCa) is the 3rd leading cause of death from cancer in men and constitutes almost 1/4 of all new cancer cancers in men. Although PCa is prevalent, the risk of clinical or fatal PCa in a 50 year old man is estimated at only 10% and 3%, respectively Currently, over 2/3 of men diagnosed with PCa are diagnosed with organ confined, low risk disease (PSA < 10 ng/ml, Gleason score (=GS) 3+3, cT1c). Management is depending on tumour grade, size and stage and clinical parameters (e.g. life expectancy) and may range from active surveillance to radical therapy including definitive whole gland treatment (radical prostatectomy (RP), or radiation therapy). Although radical whole gland therapy is effective from an oncological standpoint, it may be associated with significant side effects. A more conservative approach in select patients may be enrollment in an active surveillance program. The concept behind this approach is that small volume, low grade PCa may have an indolent course and may not progress to biological significance in the absence of treatment in the patient's lifetime.

Conventional workup of patients with clinical suspicion of PCa:

Transrectal Ultrasound (TRUS)-guided biopsies: Current workup of patients with clinical suspicion of PCa includes TRUS-guided systematic biopsies. These are associated with a relatively high false negative rate, especially for areas difficult to access for biopsy, with csPCa missed in approximately 1 of 4 patients. Furthermore, there is only ˜50% correlation between biopsy obtained GS and final pathology at RP, with upgrading in more than 1 in 3 cases. This may lead to inaccurate risk stratification and inappropriate selection of therapy.

Role of multiparametric-MR & MR-Ultrasound Fusion Biopsy:

In recent years, multiparametric MR (mpMR) has been incorporated in the workup of patients with suspected PCa. T2- weighted imaging (T2WI) in combination with diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE)-MR have shown promise in the detection, local staging and risk stratification of PCa, with a reported sensitivity and specificity of 0.74 & 0.88, respectively. Prostate MR is interpreted using a 5-point scoring scale (PI-RADS - Prostate Imaging and Reporting Archiving Data System), with an overall sensitivity & specificity of 77.0% & 71.4%, respectively, for detection of csPCa using PI-RADS-v2. Using MR-US fusion targeted biopsy for mpMR detected lesions improves detection of csPCa compared to standard biopsy (median: 9.1%) and improves correlation of biopsy-derived and surgical tumour grade.

Focal ablation therapy:

In recent years, trials have evaluated various focal ablative therapies (FT) as alternative management for select patients with low/ intermediate risk, organ-confined disease. FT for PCa involves varying degrees of predefined subtotal glandular ablation using a myriad of ablative energy sources e.g high intensity focused ultrasound (HIFU), or laser ablation. The common aim of all of these methods is curative-intent tumour ablation while minimizing morbidity, thereby potentially providing the best balance between oncologic control and side effects of radical therapy. FT relies on the notion that the index lesion can be identified by mpMRI, and localized for intervention. Although no long term data exists on the safety and oncologic outcome of FT, FT appears well-tolerated and associated with significantly less morbidity than whole-gland treatment. At our institution, in-bore focal laser ablation program (MRgFLT) allows patients with a single site of csPCa to be treated while the in-bore HIFU program allows inclusion of patients with up to 2 sites of csPCa confirmed on MR-TRUS fusion biopsy.

One of the main risks with a strategy of FT in PCa is selection failure. Although data is scarce, residual or unrecognized cancer was detected on follow-up biopsy in 22-50% of patients from two separate small series, including cancers in portions of the prostate not appreciated prior to intervention. Although it is uncertain how many of these are csPCa, this highlights the potential limitations of current workup algorithms for patients considered for FT. As only recognized index tumour site is targeted, detection of any further site of csPCa is paramount for appropriate patient selection and therapy success.

Molecular imaging in PCa:

There are shortcomings of current workup of patients with clinical suspicion of PCa, including significant false negative rate of TRUS-biopsies and mpMR. At least 1 in 5 patients in active surveillance program thought to have low-risk disease based on biopsies, turns out to have unfavorable features on surgical pathology. As specific patient management is based on accurate risk stratification, there is a clinical need for further tools to improve identification and characterization of csPCa. There has been increasing interest in molecular imaging in PCa in recent years. The most common radiopharmaceuticals used include choline (11C-Choline/ 18F-Fluorocholine) and 68Ga-PSMA.

PSMA, a type II transmembrane protein, is expressed in normal prostate epithelium and highly expressed in ~90% primary PCa and metastases. 68Ga-PSMA-HBED-CC, the most common PSMA PET radiopharmaceutical assessed to date, has shown high sensitivity in detecting recurrent disease. Recently developed 18F-labelled PSMA compounds (e.g. 18F-DCFPyL) offer several technical advantages over 68Ga including high imaging statistic and higher image resolution. Initial preclinical studies have shown favourable tissue binding and the first clinical investigation in 9 patients has shown very high levels of uptake in primary tumours and metastases with further pilot data suggesting additional metastases identified in >20% of patients compared to 68Ga-PSMA.

Recently introduced hybrid PET/MR scanners allow simultaneous acquisition of MR & PET data, incorporation the advantages of MR and molecular imaging. Emerging data is showing PET/MR to be potentially robust for assessment of oncology indications, particularly those that are better addressed with MR such as PCa. A recently published trial on 68Ga-PSMA PET/MR in intermediate-high risk patients has shown that mpMR, PET and PET/MR had a sensitivity of 66%, 92% and 98%, respectively in localizing Pca. PSMA-PET may also help characterize equivocal lesions on mpMR (PI-RAD v.2 score 3) and may facilitate targeted fusion biopsies of lesions not seen on MR.

Voir cet essai sur ClinicalTrials.gov

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