Joyce G. R. Bomers

MR Imaging–guided Focal Cryoablation in Patients with Recurrent Prostate Cancer

PURPOSE To assess the feasibility of magnetic resonance (MR) imaging-guided focal cryoablation in patients with locally recurrent prostate cancer after radiation therapy. MATERIALS AND METHODS This was a prospective study, and informed consent was obtained from all patients. Ten consecutive patients with histopathologically proved recurrent prostate cancer after radiation therapy, without evidence of distant metastases, were treated while under general anesthesia in a 1.5-T MR unit. A urethral warmer was inserted. Cryoneedles were transperineally inserted under real-time MR imaging. Then, a rectal warmer was inserted. Ice ball growth was continuously monitored under MR imaging guidance. Two freeze-thaw cycles were performed. Follow-up consisted of a visit to the urologist, measurement of prostate-specific antigen level, and multiparametric MR imaging at 3, 6, and 12 months. Potential complications were recorded. RESULTS All patients were successfully treated. In one patient, the urethral warmer could not be inserted and the procedure was cancelled. Two months later, the procedure was successfully repeated. Another patient had urinary retention. Follow-up data were available for all patients. A local recurrence or remnant tumor was found in two patients after 6 months and in another patient after 12 months. These three patients underwent successful retreatment with MR imaging-guided focal cryoablation. CONCLUSION MR imaging-guided focal cryoablation of recurrent prostate cancer after radiation therapy is feasible and safe. Initial results are promising; however, longer follow-up is needed and more patients must be studied.

Predictive value of MRI in the localization, staging, volume estimation, assessment of aggressiveness, and guidance of radiotherapy and biopsies in prostate cancer.

Multiparametric magnetic resonance imaging (MRI) has the potential of being the ideal prostate cancer (PCa) assessment tool. Information gathered with multiparametric MRI can serve therapy choice, guidance of interventions, and treatments. The purpose of this review is to discuss the potential role of multiparametric MRI in focal therapy with respect to patient selection and directing (robot‐guided) biopsies and intensity‐modulated radiation therapy (IMRT). Multiparametric MRI is a versatile and promising technique. It appears to be the best available imaging technique at the moment in localizing, staging (primary as well as recurrent disease, and local as well as distant disease), determining aggressiveness, and volume of PCa. However, larger study populations in multicenter settings have to confirm these promising results. However, before such studies can be performed more research is needed in order to achieve standardized imaging protocols. J. Magn. Reson. Imaging 2012;35:20‐31.

MRI-Guided Interventions for the Treatment of Prostate Cancer

OBJECTIVE The purpose of this article is to evaluate MRI-guided therapies and to investigate their feasibility for focal therapy in prostate cancer patients. Relevant articles were retrieved using the PubMed online search engine. CONCLUSION Currently, MRI-guided laser ablation and MRI-guided focused ultrasound are the most promising options for focal treatment of the prostate in patients with prostate cancer. Other techniques-that is, cryosurgery, microwave ablation, and radiofrequency ablation-are, for several and different reasons, less suitable for MRI-guided focal therapy of the prostate.

Standardization of Multiparametric Prostate MR Imaging Using PI-RADS

The purpose of this paper is to introduce and describe the Prostate Imaging and Reporting Archiving Data System (PI-RADS). For every single parameter the PI-RADS scoring system will be explained and magnetic resonance imaging (MRI) examples will be given. In the end two patient cases are presented to explain the overall interpretation score in multiparametric imaging.

Diffusion-weighted magnetic resonance imaging in the prostate transition zone: histopathological validation using magnetic resonance-guided biopsy specimens

ObjectivesThe objective of this study was to evaluate the apparent diffusion coefficient (ADC) of diffusion-weighted magnetic resonance (MR) imaging for the differentiation of transition zone cancer from non-cancerous transition zone with and without prostatitis and for the differentiation of transition zone cancer Gleason grade (GG) using MR-guided biopsy specimens as a reference standard. Materials and MethodsFrom consecutive MR-guided prostate biopsies (2008–2012) in our referral center, we retrospectively included patients from whom diffusion-weighted MR imaging ADC values were acquired during MR-guided biopsy and whose biopsy cores had a (cancer) core length 10 mm or greater and originated from the transition zone. Two radiologists, who were blinded to the ADC data, annotated regions of interest on biopsy sampling locations of MR-guided biopsy confirmation scans in consensus. Median ADC (mADC) of the regions of interest was related to histopathology outcome in MR-guided biopsy core specimens. Mixed model analysis was used to evaluate mADC differences between 7 histopathology categories predefined as MR-guided biopsy core specimens with primary and secondary GG 4–5 (I), primary GG 4–5 secondary GG 2–3 (II), primary GG 2–3 secondary GG 4–5 (III) and primary and secondary GG 2–3 cancer (IV), and noncancerous tissue without (V) or with degree 1 (VI) or degree 2 prostatitis (VII). Diagnostic accuracy was evaluated using areas under the receiver operating characteristic (AUC) curve. ResultsFifty-two patients with 87 cancer-containing biopsy cores and 53 patients with 101 non-cancerous biopsy cores were included. Significant mean mADC differences were present between cancers (mean mADC, 0.77–0.86 × 10−3 mm2/s) and noncancerous transition zone without (1.12 × 10−3 mm2/s) and with degree 1 to 2 prostatitis (1.05–1.12 × 10−3 mm2/s; P < 0.0001–0.05). Exceptions were mixed primary and secondary GG cancers versus a degree 2 of prostatitis (P = 0.06–0.09). No significant differences were found between subcategories of primary and secondary GG cancers (P = 0.17–0.91) and between a degree 1 and 2 prostatitis and non-cancerous transition zone without prostatitis (P = 0.48–0.94).The mADC had an AUC of 0.84 to differentiate cancer versus non-cancerous transition zone. AUCs of 0.84 and 0.56 were found for mADC to differentiate prostatitis from cancer and from non-cancerous transition zone. The mADC had an AUC of 0.62 to differentiate a primary GG 4 versus GG 3 cancer. ConclusionsThe mADC values can differentiate transition zone cancer from non-cancerous transition zone and from a degree 1, and from most cases of a degree 2 prostatitis. However, because of substantial overlap, mADC has a moderate accuracy to differentiate between different primary and secondary GG subcategories and cannot be used to differentiate non-cancerous transition zone from degrees 1 to 2 of prostatitis. Diffusion-weighted imaging ADC may therefore contribute in the detection of transition zone cancers; however, as a single functional MR imaging technique, diffusion-weighted imaging has a moderate diagnostic accuracy in separating higher from lower GG transition zone cancers and in differentiating prostatitis from non-cancerous transition zone.

Results of Targeted Biopsy in Men with Magnetic Resonance Imaging Lesions Classified Equivocal, Likely or Highly Likely to Be Clinically Significant Prostate Cancer

BACKGROUND The Prostate Imaging Reporting and Data System (PI-RADS) is the most commonly used scoring system in prostate magnetic resonance imaging (MRI). One of the available techniques to target suspicious lesions is direct in-bore MRI-guided biopsy (MRGB). OBJECTIVE To report on the experience and results of MRGB in a large cohort of patients with lesions classified as equivocal (PI-RADS 3), likely (PI-RADS 4), or highly likely (PI-RADS 5) to be clinically significant (cs) prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS We retrospectively included 1057 patients having MRGB, between January 2012 and September 2016, of lesions classified as PI-RADS≥3 on multiparametric MRI. Biopsy-naïve patients, patients with prior negative systematic transrectal ultrasound-guided biopsy, and patients in active surveillance were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome measurement is the detection rate of csPCa. Descriptive statistics and chi-square tests were used to calculate the differences in proportions. We considered a Gleason score of ≥3+4 as csPCa. RESULTS AND LIMITATIONS PCa was diagnosed in 35% (55/156), 60% (223/373), and 91% (479/528), and csPCa in 17% (26/156), 34% (128/373), and 67% (352/528) of patients with PI-RADS 3, 4, and 5 lesions, respectively. Follow-up of patients with negative biopsy findings resulted in csPCa in 1.7% (5/300) after a median period of 41 (interquartile range 25-50) mo. The evaluation of prostate-specific antigen density (PSAD) to predict csPCa resulted in 42% of patients with a PI-RADS 3 lesion who could avoid biopsy in case a PSAD of ≥ 0.15ng/ml/ml would be used. In 6% (95% confidence interval, 2-15), csPCa would then be missed. The study is limited because of its retrospective character. CONCLUSIONS MRGB in lesions scored PI-RADS≥3 yields high detection rates of csPCa in daily clinical practice in cases with previous negative biopsy. PATIENT SUMMARY In daily clinical practice, direct in-bore magnetic resonance imaging-guided biopsy of suspicious lesions reported according to the Prostate Imaging Reporting and Data System yields high detection rates of clinically significant prostate cancer.

Location of Prostate Cancers Determined by Multiparametric and MRI-Guided Biopsy in Patients With Elevated Prostate-Specific Antigen Level and at Least One Negative Transrectal Ultrasound–Guided Biopsy

OBJECTIVE The purpose of this article is to identify histopathologically proven prostate cancer locations using MRI followed by MRI-guided biopsy in patients with elevated prostate-specific antigen (PSA) levels and at least one negative transrectal ultrasound (TRUS)-guided biopsy session. Our hypothesis is that in this patient group most cancers are located in the anterior portion of the prostate. This may have implications for the biopsy strategy regarding the location of sampling. MATERIALS AND METHODS This retrospective study consisted of 872 consecutive men who had undergone MRI-guided prostate biopsy. Inclusion criteria were PSA level greater than or equal to 4 ng/mL, one or more negative TRUS-guided biopsy session, the presence of suspicious lesions on previous multiparametric MRI, and prostate cancer histopathologically proven by MRI-guided biopsy. Thereafter, the location of intermediate- or high-risk cancers and cancers with a maximum cancer core length of 6 mm or longer were determined. The proportion of cancer locations was compared using a chi-square test. One-way ANOVA analyses were performed to compare patient characteristics. RESULTS Results were presented on both a patient and lesion basis because a single patient can have multiple lesions. In total, 176 of 872 patients met the inclusion criteria. Prostate cancer was detected in 202 of 277 (73%) suspicious lesions. In total, 76% of patients had cancer of the transition zone and anterior fibromuscular stroma. Peripheral zone cancers were found in 30% of the patients, and 6% had cancers in both zones. In 70% of cases (141/202; 95%, CI, 63-76%), lesions were located anteriorly; this included 75% (132/176; 95%, CI, 69-81%) of patients. Intermediate- or high-risk prostate cancer was found in 93% (128/138; 95%, CI, 88-96%) of patients. Of these patients, 73% (94/128; 95%, CI, 66-81%) had anterior involvement. Cancers with a maximum cancer core length of 6 mm or more were more likely to be located in the anterior part of the prostate than were cancers with a core length of less than 6 mm (66% vs 6%). Most cancers 58% (102/176; 95% CI, 51-65%) were found in the mid prostate. Anterior involvement of prostate cancer detected by MRI-guided biopsy was statistically significantly (p = 0.04) higher in patients with two or more negative TRUS-guided biopsy sessions (79%) than in those with one negative TRUS-guided biopsy session (55%). CONCLUSION Anterior involvement was high (76%) in patients with an elevated PSA level and one or more negative TRUS-guided biopsy session, and the majority of these cancers (93%) were intermediate or high risk.

Quantitative identification of magnetic resonance imaging features of prostate cancer response following laser ablation and radical prostatectomy

Abstract. Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. In this study, for the first time, we are integrating ex vivo pathology and magnetic resonance imaging (MRI) to assess the imaging characteristics of prostate cancer and treatment changes following LITT. Via a unique clinical trial, which gave us the availability of ex vivo histology and pre- and post-LITT MRIs, (1) we investigated the imaging characteristics of treatment effects and residual disease, and (2) evaluated treatment-induced feature changes in the ablated area relative to the residual disease. First, a pathologist annotated the ablated area and the residual disease on the ex vivo histology. Subsequently, we transferred the annotations to the post-LITT MRI using a semi-automatic elastic registration. The pre- and post-LITT MRIs were registered and features were extracted. A scoring metric based on the change in median pre- and post-LITT feature values was introduced, which allowed us to identify the most treatment responsive features. Our results show that (1) image characteristics for treatment effects and residual disease are different, and (2) the change of feature values between pre- and post-LITT MRIs can be a quantitative biomarker for treatment response. Finally, using feature change improved discrimination between the residual disease and treatment effects.

Distinguishing benign confounding treatment changes from residual prostate cancer on MRI following laser ablation

Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. However, very little is known about the specific effects of LITT within the ablation zone and the surrounding normal tissue regions. For instance, it is important to be able to assess the extent of residual cancer within the prostate following LITT, which may be masked by thermally induced benign necrotic changes. Fortunately LITT is MRI compatible and hence this allows for quantitatively assessing LITT induced changes via multi-parametric MRI. Of course definite validation of any LITT induced changes on MRI requires confirmation via histopathology. The aim of this study was to quantitatively assess and distinguish the imaging characteristics of prostate cancer and benign confounding treatment changes following LITTon 3 Tesla multi-parametric MRI by carefully mapping the treatment related changes from the ex vivo surgically resected histopathologic specimens onto the pre-operative in vivo imaging. A better understanding of the imaging characteristics of residual disease and successfully ablated tissue might lead to improved treatment monitoring and as such patient prognosis. A unique clinical trial at the Radboud University Medical Center, in which 3 patients underwent a prostatectomy after LITT treatment, yielded ex-vivo histopathologic specimens along with pre- and post-LITT MRI. Using this data we (1) identified the computer extracted MRI signatures associated with treatment effects including benign necrotic changes and residual disease and (2) subsequently evaluated the computer extracted MRI features previously identified in distinguishing LITT induced changes in the ablated area relative to the residual disease. Towards this end first a pathologist annotated the ablated area and the residual disease on the ex-vivo histology and then we transferred the annotations to the post-LITT MRI using semi-automatic elastic registration. The pre- and post-LITT MRI were subsequently registered and computer-derived multi-parametric MRI features extracted to determine differences in feature values between residual disease and successfully ablated tissue to assess treatment response. A scoring metric allowed us to identify those specific computer-extracted MRI features that maximally and differentially expressed between the ablated regions and the residual cancer, on a voxel- by voxel basis. Finally, we used a Fuzzy C-Means algorithm to assess the discriminatory power of these selected features. Our results show that specific computer-extracted features from multi-parametric MRI differentially express within the ablated and residual cancer regions, as evidenced by our ability to, on a voxel-by-voxel basis, classify tissue as residual disease. Additionally, we show that change of feature values between pre- and post-LITT MRI may be useful as a quantitative marker for treatment response (T2-weighted texture and DCE MRI features showed largest differences between residual disease and successfully ablated tissue). Finally, a clustering approach to separate treatment effects and residual disease incorporating both (1) and (2) yielded a maximum area under the ROC curve of 0.97 on a voxel basis across 3 studies.