Joseph C. Liao and Li-Ming Su (eds.)Advances in Image-Guided Urologic Surgery10.1007/978-1-4939-1450-0_14

14. MR-Guided Prostate Interventions

Ashley E. Ross¹, Dan Stoianovici² and Mohamad E. Allaf³

(1)

Departments of Urology, Oncology, Pathology, Johns Hopkins Brady Urological Institute, Baltimore, MD, USA

(2)

Departments of Urology, Mechanical Engineering, and Neurosurgery, Johns Hopkins Brady Urological Institute, Baltimore, MD, USA

(3)

Departments of Urology, Oncology, and Biomedical Engineering, Johns Hopkins Brady Urological Institute, Baltimore, MD, USA

Ashley E. Ross

Email: aross2@jhmi.edu

Dan Stoianovici (Corresponding author)

Email: dss@jhu.edu

Keywords

Magnetic resonance imaging for prostateProstate CancerHigh Intensity Focused Ultrasound and prostate cancerCryotherapy for prostate cancerLaser Ablation for prostate cancerFocal Therapy for prostate cancerMRI for prostate cancer

Prostate cancer represents the most common visceral malignancy in man, with roughly 240,000 patients diagnosed in the United States last year and 1 in every 36 men dying of the disease [1]. Widespread use of PSA screening has resulted in the earlier detection of prostate cancer and has contributed to the nearly 40 % decrease in prostate cancer mortality since its peak in 1991 [2]. Associated with this has been a greater likelihood of diagnosis of prostate cancer at a clinically localized stage, with a nearly tenfold reduction in the amount of men diagnosed with metastatic disease since the start of the PSA era and thus the vast majority of men currently being diagnosed with localized prostate cancer. Despite these advances, due to the lead time associated with PSA-based screening, and its relative inability to distinguish patients with indolent and life-threatening cancers, there is a growing concern for overdiagnosis and overtreatment in screened populations [3–5]. Indeed, the majority of patients currently diagnosed with prostate cancer have low-grade (Gleason pattern 3 or less), favorable-risk disease and, if not upgraded at the time of surgery, might have low cancer-specific mortality even without intervention [6, 7]. Regardless, there is a rationale for the use of definitive local therapy, as up to 30 % of men with low-risk disease will be upgraded at prostatectomy [8]. Indeed, trepidation regarding the undertreatment of a known but possibly under-sampled malignancy has led to an underuse of active surveillance of low-risk disease [9]. Unfortunately, current whole-gland treatment of prostate cancer is associated with the risk of long-term urinary and sexual side effects and decreased quality of life [10]. For these reasons, there has been a growing emphasis on the development of focal therapies which may treat prostate cancer or the index prostatic lesion while limiting damage to the urethral sphincter and neurovascular bundles. However, while the “male lumpectomy” for prostate cancer was originally proposed by Onik and colleagues two decades ago, adoption of focal ablation for prostate cancer treatment has been slow, in part due to the inability of imaging modalities to adequately identify localized prostate cancer [11, 12].

Relatively recent advances in multiparametric MRI imaging now allow for the localization of larger (≥0.5 cm) prostate cancer lesions with relatively high sensitivity and specificity and have become the gold standard for imaging disease within the prostate. This thus allows for improved patient selection for subtotal and focal therapies. In addition, use of specialized MRI sequences allows not only for patient selection and treatment planning but also for true focal therapy with treatment guidance, real-time treatment monitoring, and posttreatment evaluation. Below we review the features of prostate MRI and discuss MRI-guided interventions to treat prostate cancer, focusing on the modalities of high-intensity-focused ultrasound (HIFU), laser thermoablation, and cryoablation.

Magnetic Resonance Imaging of the Prostate

MRI of the prostate was first reported in the mid-1980s and has since evolved to provide both anatomical and also functional information [13]. Anatomic information is provided primarily via T2-weighted imaging, which allows for high spatial resolution and very clearly identifies the distinct zones of the prostate. On T2-weighted imaging, prostate cancer can appear as an area of low signal within the normally high-signal peripheral zone. Historically, MRI was performed using a 1.5 Tesla (T) scanner and an endorectal coil. The introduction of higher strength (3 T) magnets allowed for higher spatial resolution. This prompted many radiologists to perform 3 T scans in the absence of endorectal coil, making MRI more tolerable by patients [14]. T2-weighted imaging is limited in that areas of low signal can also represent prostatitis, biopsy tracts, and other benign abnormalities. Because of this, a recent consensus panel for the use of focal therapy in prostate cancer recommends that staging MRI be performed with a 3 T magnet and in a multiparametric fashion using T1-, T2-, and diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) [14]. The use of these combinations allows for high specificity, positive and negative predictive value (all over 90 %) albeit with lower sensitivities (~60 %) [14, 15].

DWI examines proton diffusion properties of water within prostate tissue to determine an apparent diffusion coefficient (ADC). In cases of prostate cancer, where cellular density is increased thus restricting the movements of water, ADCs are lower than in benign tissue. DWI can be determined without the use of contrast and can be obtained rapidly. The ADC also changes with treatment, and DWI can be used to actively monitor the development of ablated tissue during treatment [16]. While very practical, the use of DWI is limited by its susceptibility to motion artifact.

As its name implies, DCE involves the use of contrast and its monitoring by T1-weighted sequences. Contrast-enhanced imaging can identify neovascularization of tumors by looking at the time to peak enhancement, level of peak enhancement, and washout. As ablation of the prostate alters these characteristics by causing necrosis, fibrosis, inflammation, and devascularization, DCE can be performed following treatment to gauge the extent of ablation with hypo-vascular tissue generally appearing hypointense on T1 [17].

In addition to DWI and DCE, magnetic resonance spectroscopic imaging has also been explored as part of mpMRI. Spectroscopic imaging can demonstrate relative concentrations of citrate, creatine, and choline of which prostate cancer tends to have lower and higher levels, respectively, compared to normal tissue [17]. While multiple studies demonstrate an added value of spectroscopic imaging to T2-weighted imaging alone, it is technically demanding and has low reproducibility, limiting its routine use [14].

Beyond providing cancer detection and 3D imaging information, MRI can also be used for temperature monitoring during thermal ablation. This is most commonly performed by temperature monitoring via proton-resonant frequency shift thermometry [18, 19]. This technique takes advantage of the temperature dependence for the water proton chemical shift and allows for highly reproducible, accurate, and rapid measurements of temperature change. This technique is employed for increases in temperature and cannot be readily used to study freezing due to artifacts produced at the leading edge of freezing tissue [20].

MRI-Targeted Therapies for Prostate Cancer

A recently convened expert panel of urologists, radiologists, and basic researchers from Europe and North America concluded that mpMRI is an important component of patient selection for focal therapy [14]. While these conclusions were based on considerations for primary prostate cancer treatment, MRI can additionally play a valuable role in targeting salvage therapies both after radiation and surgical treatment. Below we focus on three emerging modalities for targeted therapy based on their ability to be integrated with MRI and their acceptance as ablative modalities. Additionally, it is important to highlight that all of the MRI-guided interventions discussed below have only been examined in relatively small safety and feasibility studies and further that the concept of focal therapy itself, despite mounting evidence, has not been accepted by the AUA and should still be considered experimental in nature.

MRI-Guided High-Intensity-Focused Ultrasound (HIFU) Therapy for Prostate Cancer

HIFU is a form of thermoablation whereby piezoelectric transducers are used to generate a focused ultrasound field. This allows the temperature to rise quickly in the focal zone of treatment, while the surrounding tissue, which is exposed to unfocused low acoustic energy, is unaffected [21]. Heating of tissue to over 55 °C causes cytotoxic effects and results in coagulative necrosis [22]. HIFU can be performed either transrectally or transurethrally and, as it requires no incision or puncture, represents the most externally noninvasive treatment modality available for prostate cancer. In addition, HIFU, as another ablative therapy, can be performed within the MRI (“in bore”) with real-time MR imaging or by fusing a previously obtained MR image onto an ultrasound. The advantage of in-bore techniques is that real-time image acquisition and therapeutic guidance can be employed. In addition, in-bore techniques allow for the use of thermal monitoring and adjustment of treatment. A disadvantage to in-bore techniques is that they are costly and can be resource and time intensive. Fusion techniques offer a less costly alternative but can be inaccurate and real-time monitoring of ablation is not possible.

Recently, Dickinson and colleagues reported on 26 men undergoing focal HIFU using the Sonablate 500 system and nonrigid registration software to couple US and mpMRI imaging [23]. This represented a pilot study, nested within the INDEX trial, a multicentered investigator-driven trial in the United Kingdom to observe the 3-year outcomes following HIFU. Here they demonstrated feasibility of using HIFU and fusion software for MR and ultrasound imaging with no technical difficulties experienced while using the fusion software during HIFU. Mean overall operative time was 141 min. Postoperative histologic and oncologic outcomes were not reported; however, the decision to ablate additional tissue outside of the initial treatment plan was made in half the cases. This highlights the uncertainly inherent in fusion imaging and lack of real-time ablation visualization.

In order to facilitate real-time temperature feedback and ablation localization and monitoring, transurethral HIFU therapies have been developed that are coupled to MRI. The feasibility of such a technique was shown first in canines and then extended to a pilot phase 0 study in humans [24, 25]. In this study, Chopra et al. treated eight men with localized prostate cancer immediately prior to prostatectomy by transurethral HIFU. In their system, the transurethral ultrasound heating applicator was coupled to a MRI-compatible rotational positioning system which additionally had circulating deionized water in a flowing circuit to allow cooling and coupling across the urethra. The transducer emits linear beams with rotation allowing selection of the ablated volume. By design in this feasibility study, the peripheral zone was not treated, and accordingly no rectal cooling was used. Following treatment men were taken immediately to prostatectomy, and prostates were step sectioned as whole mounts to compare to MRI ablation images. The average treatment time was 3 h, and the accuracy of the treatment zone was concordant to roughly 2.5 mm. Histologic analysis showed a contiguous treatment area with a transition zone from ablated to normal tissue of less than 4 mm. In a subsequent canine study using a similar prototype MRI-guided US therapy system developed by Philips, treatments were extended to all of the zones of the prostate including the peripheral zone [16]. This study demonstrated ablation of the peripheral zone and high correlation of ablation with posttreatment MRI imaging, as measured by DWI or DCE compared to histology (r ² of 0.91 and 0.89, respectively).

Recently, a small MR-coupled transrectal HIFU study prior to prostatectomy was also reported [26]. In this study, HIFU was used with a 3 T MRI and temperature monitoring by proton frequency shift. Of the five patients treated that underwent immediate prostatectomy, all had untreated prostate cancer in their specimen with two having clinically significant tumors outside the treatment zone.

While the above studies demonstrate the technical feasibility of real-time MRI-targeted focal therapy of the prostate, the actual clinical utility of this method remains a matter for further study. A clear case can be made for the benefit of mpMRI in appropriately selecting men for subtotal gland ablation; however, the argument for a need of true focal therapy (as oppose to hemi-ablation or other subtotal ablation) is more debatable. In part, this is due to the anatomy of the prostate. The prostate gland itself serves minimal function but is situated in an important area, surrounded distally and anteriorly by the striated urethral sphincter and posterolaterally by the neurovascular bundles of Walsh. Ablation of prostate tissue per say is of no or minimal consequence, and partial ablation of the urethral sphincter or one of two redundant neurovascular bundles may have only marginal effects. Indeed, in 2011, Ahmed et al. reported results of a phase I/II trial of 20 men with low- to intermediate-risk prostate cancer who underwent hemi-ablation of the prostate by HIFU after having mpMRI and template trans-perineal prostate biopsies to confirm unilateral disease [27]. In this small series, 95 % of men preserved potency, 95 % were continent, and 89 % had no histological evidence of cancer after 1 year of follow-up. Currently, larger studies with longer follow-up comparing focal therapy to hemi-ablation therapy are needed in order to determine whether focal therapy can improve outcomes over subtotal or hemi-gland ablation while preserving oncologic efficacy.

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