Focal Therapy Research Articles

878 - Assessing focality of dominant tumor on serial biopsy in an active surveillance cohort - implications for focal therapy

878 - Assessing focality of dominant tumor on serial biopsy in an active surveillance cohort - implications for focal therapy

PT002 - Multiparametric MRI of the prostate significantly underestimates tumor volume of small visible lesions. Implications for tailored focal therapy approaches

PT002 - Multiparametric MRI of the prostate significantly underestimates tumor volume of small visible lesions. Implications for tailored focal therapy approaches

886 - Focal therapy for localized prostate cancer with mpMRI/US fusion-guided radiofrequency ablation: Oncologic and functional outcomes

886 - Focal therapy for localized prostate cancer with mpMRI/US fusion-guided radiofrequency ablation: Oncologic and functional outcomes

891 - The relationship between percentage PSA reduction and rate of failure after focal therapy for prostate cancer

891 - The relationship between percentage PSA reduction and rate of failure after focal therapy for prostate cancer

879 - Is focal ablation as effective as hemi-ablation? Analysis of treatment patterns over 12 years from a high volume centre for focal therapy

879 - Is focal ablation as effective as hemi-ablation? Analysis of treatment patterns over 12 years from a high volume centre for focal therapy

892 - Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: A propensity matched study

892 - Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: A propensity matched study

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Role of multiparametric prostate MRI in the management of prostate cancer.

Prostate cancer has traditionally been diagnosed by an elevation in PSA or abnormal exam leading to a systematic transrectal ultrasound (TRUS)-guided biopsy. This diagnostic pathway underdiagnoses clinically significant disease while over diagnosing clinically insignificant disease. In this review, we aim to provide an overview of the recent literature regarding the role of multiparametric MRI (mpMRI) in the management of prostate cancer. A thorough literature review was performed using PubMed to identify articles discussing use of mpMRI of the prostate in management of prostate cancer. The incorporation of mpMRI of the prostate addresses the shortcomings of the prostate biopsy while providing several other advantages. mpMRI allows some men to avoid an immediate biopsy and permits visualization of areas likely to harbor clinically significant cancer prior to biopsy to facilitate use of MR-targeted prostate biopsies. This allows for reduction in diagnosis of clinically insignificant disease as well as improved detection and better characterization of higher risk cancers, as well as the improved selection of patients for active surveillance. In addition, mpMRI can be used for selection and monitoring of patients for active surveillance and treatment planning during surgery and focal therapy.

Can ultrasound irradiation be a therapeutic option for prostate cancer?

Focal therapies for prostate cancer (PC) can reduce adverse events and do not lead to androgen-independent progression. Ultrasound could be used for cancer treatments if the repetition frequency is fitted to the purpose. We investigated the possible therapeutic effect of ultrasound irradiation on PC cells. We irradiated two PC cell lines, androgen-dependent LNCaP and -independent PC-3 with ultrasound (3.0 W/cm2 , 3 MHz, irradiation time rate: 20%) for 2 minutes for 1 day or 3 consecutive days at a repetition frequency of 1, 10, or 100 Hz in vitro. Cell proliferation and apoptosis were determined after irradiation. Cell proliferation of PC-3 was significantly inhibited after 1 day (P < .0001) and 3 days (P < .0001) of 10 Hz ultrasound irradiation, and that of LNCaP after 1 day (P < .0001) and 3 days (P < .0001) of irradiation. LNCaP was more sensitive to ultrasound at both lower and higher cell density but PC-3 was only sensitive at a lower cell density (P < .01). Irradiation with 10 Hz ultrasound-induced significantly more PC-3 apoptotic cells than control (1 day, P = .0137; 3 days, P = .0386) rather than irradiation with 1 Hz. Apoptosis via caspase-3 was induced at 10 Hz in 1-day (P < .05) irradiation in both cell lines. Ultrasound irradiation with even 1 day of 10 Hz significantly inhibited cell proliferation in both LNCaP and PC-3, especially by the remarkable induction of apoptosis in vitro. Our study indicated that ultrasound irradiation can be a therapeutic option for PC and further studies in vivo will be undertaken.

Focal therapy with high-intensity focused ultrasound for the localized prostate cancer for Asian based on the localization with MRI-TRUS fusion image-guided transperineal biopsy and 12-cores transperineal systematic biopsy: prospective analysis of oncological and functional outcomes.

We evaluated clinical outcomes of region target focal therapy with high-intensity focused ultrasound (HIFU) for the localized prostate cancer (PCa) based on magnetic resonance imaging-based biopsy and systematic prostate biopsy for Asian. We prospectively recruited patients with localized PCa, located their significant tumors using MRI-transrectal ultrasound (TRUS) elastic fusion image-guided transperineal prostate biopsy and 12-cores transperineal systematic biopsy, and focally treated these regions in which the tumors were located in the prostate using HIFU. Patients' functional and oncological outcomes were analyzed prospectively. We treated 90 men (median age 70years; median PSA level 7.26ng/ml). Catheterization was performed within 24h after the treatment in all patients. Biochemical disease-free rate was 92.2% during 21months follow-up when use of Phoenix ASTRO definition. In follow-up biopsy, significant cancer was detected in 8.9% of the patients in un-treated areas. Urinary functions, including international prostate symptom score (IPSS) (P < 0.0001), IPSS quality of life (QOL) (P = 0.001), overactive bladder symptom score (OABSS) (P < 0.0001), EPIC urinary domain (P < 0.0001), maximum urinary flow rate (P < 0.0001), and IIEF-5 (P = 0.001), had significantly deteriorated at 1month after treatment, but improved to preoperative levels at 3 or 6months. Rates of erectile dysfunction and ejaculation who had the functions were 86% and 70%, respectively, at 12months after treatment. The present treatment for Asian would have similar oncological and functional outcomes to those in previous reports. Further large studies are required to verify oncological and functional outcomes from this treatment for patients with localized PCa.

Making a case "against" focal therapy for intermediate-risk prostate cancer.

Focal therapy (FT) for localized prostate cancer (PCa) is a promising treatment strategy. Although, according to guidelines, it should be regarded as an experimental option, its introduction into clinical practice has occurred at an accelerated speed. It is, thus, crucial for Urologists to understand FT limitations and potential drawbacks that may derive from its use. We performed a literature search of peer-reviewed English language articles using Pubmed and the words "focal therapy" AND "prostate cancer" to identify relevant articles. Web search was complemented by manual search. From a biological perspective, in contrast with the index lesion theory, which still needs to be better supported, PCa is a multifocal and multiclonal entity. Also, the effects of FT on PCa microenvironment are unclear. From a clinical perspective, patient selection is still not precisely defined. Even when all variables potentially decreasing mpMRI and biopsy accuracy are optimized, up to one out of two men may be incorrectly selected for FT, leaving a significant proportion of clinically significant PCa (csPCa) untreated. Underestimation of PCa volume and variant histologies are other additional mpMRI potential limitations. No RCTs have been performed against the standard of care to support FT. There is absence of long-term results and FT series reaching medium-term follow-up have non-optimal oncological control with significant re-treatment needs. When PCa recurs/persists after FT, little is known about the appropriate management strategies and their outcomes. Finally, the optimal follow-up scheme post-FT remains unclear. Several arguments are present against the use of FT for localized PCa. Studies are needed to overcome current limitations and support FT before it can be included as part of the standard management of prostate cancer.

Standardized Nomenclature and Surveillance Methodologies After Focal Therapy and Partial Gland Ablation for Localized Prostate Cancer: An International Multidisciplinary Consensus

BackgroundFocal therapy (FT) and partial gland ablation (PGA) are quickly adopted by urologists and radiologists as an option for the management of localized prostate cancer. ObjectiveTo find consensus on a standardized nomenclature and to define a follow-up guideline after FT and PGA for localized prostate cancer in clinical practice. Design, setting, and participantsA review of the literature identified controversial topics in the field of FT. Online questionnaires were distributed to experts during three rounds, with the goal to achieve consensus on debated topics. The consensus project was concluded with a face-to-face meeting in which final conclusions were formulated. Outcome measurements and statistical analysisControlled feedback of responses of previous rounds were summarized and returned to the participants allowing them to re-evaluate their decisions. The level of agreement to achieve consensus on a topic was set at 80%. Results and limitationsSixty-five experts participated in this interdisciplinary consensus study (72% urologists; 28% radiologists). The experts propose the use of the herein standardized nomenclature for ablative procedures. After FT/PGA, the following tests should be performed to assess treatment outcomes: prostate-specific antigen (PSA), imaging, biopsies, and functional outcome assessment. Although not a reliable marker for treatment failure, PSA should be measured every 3 mo in the 1st year and every 6 mo thereafter. Magnetic resonance imaging is the preferred image modality and should be performed at 6 and 18 mo after treatment. A systematic 12-core transrectal ultrasound-guided biopsy combined with a targeted biopsy of the treated area should be performed 6–12 mo after treatment. Functional outcomes should be obtained 3–6 mo after treatment for the first time and until stability is attained. ConclusionsThe panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of FT as a standard of care for select patients with localized prostate cancer. Patient summaryIn this report, we present expert opinion on the use of a standardized nomenclature, and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer.

Comparative Effectiveness of Radiotherapy versus Focal Laser Ablation in Patients with Low and Intermediate Risk Localized Prostate Cancer

At present, focal laser ablation (FLA) as a new PCa local treatment has attracted attention. We aim at comparing the survival outcomes between radiotherapy (RT) and FLA to reveal whether FLA can be used as an alternative to RT for patients with low and intermediate-risk localized PCa.We conducted analyses with data from the SEER database (2004–2015). Propensity score matching and instrumental variate (IV) were used to reduce the influence of bias and unmeasured confounders maximally.In the adjusted multivariate regression, FLA had lower overall survival (OS) benefits (HR = 1.49; 95%CI: 1.18–1.87; p < 0.001). After propensity score matching, RT still had better OS (HR = 1.50; 95%CI: 1.17–1.93; p = 0.001). The outcomes of IV-adjusted analysis showed FLA was significantly inferior to RT in OS (HR = 1.49; 95%CI: 1.18–1.87). In the subgroup analyses, for those with PSA < 4 ng/mL, FLA showed markedly worse OS and cancer-specific mortality (CSM) outcomes (OS HR = 1.89; 95%CI: 1.01–3.53; p = 0.0466 and CSM HR = 4.25; 95%CI: 1.04–17.43; p = 0.044).FLA is a promising focal therapy of PCa. But our research demonstrated RT still had an obvious advantage in survival benefits over FLA. Using FLA as an alternative treatment for RT requires careful consideration by clinicians.

Simple structural indocyanine green-loaded microbubbles for dual-modality imaging and multi-synergistic photothermal therapy in prostate cancer

As problems with the overuse of radical prostate cancer (PCa) treatment are increasingly exposed, focal therapy represents the direction of low- or intermediate-risk PCa management in the future. However, inaccurate diagnosis and low controllability of focal therapy hinder its clinical translation. In this study, we develop simple structural cyclic arginine-glycine-aspartic (cRGD) peptide-modified and indocyanine green (ICG)-loaded microbubbles (cRGD-ICG-MBs) for ultrasound-photoacoustic imaging and multi-synergistic photothermal therapy (PTT) to address the above problems. Precise PCa diagnosis is achieved by molecular ultrasound imaging. cRGD-targeting and low-frequency ultrasound with an amplitude of 500kPa convert MBs into nanoparticles for enhanced ICG delivery. Alow frequency2500 kPa amplitude ultrasound enables temporary vasculature destruction, which minimizes heat loss during PTT. Specifically, ICG in the tumor region is 14-fold higher than the control, resulting in satisfactory PTT. Our study highlights that this theranostic strategy possesses considerable clinical translational potential, especially in mini-invasive and individualized PCa therapy.

Focal therapy, time to join the multi-disciplinary team discussion?

Organ preserving management is common place in renal cancer, breast cancer and many other solid organ tumours. Current strategies in managing intermediate risk prostate cancer include either whole gland treatment, in the form of radical radiotherapy or radical prostatectomy, or active surveillance. The former is associated with significant post-treatment functional morbidity, whilst the latter associated with the burden of surveillance activity and patient anxiety. Focal therapy would logically fit as a middle ground for suitable patients in whom treatment would be recommended, but where much better functional outcomes may be possible. Ideally this comes without restricting the successful prevention of harm from the cancer. Historically limitations in developing tissue preserving focal therapy strategies in prostate cancer, were due to inaccuracies in tumour characterisation prior to treatment and during follow up. Consequently for example many patients undergoing an active surveillance strategy were being upgraded and upstaged within a short period. Recently high level evidence supporting the use of MRI and targeted biopsies, in particular the PROMIS and PRECISION trials have strengthened clinician confidence in accurate disease characterisation, thus making focal therapy to become a more feasible management option. With improved diagnostic strategies and the publication of reassuring medium term oncological and functional outcomes after focal therapy for intermediate risk prostate cancer, has the time come to require consideration of focal therapy within our multi-disciplinary team (MDT) meetings and with patients? In this review we will consider patient selection and the evidence for the various focal ablation options as well as the surveillance of these patients after treatment. The forthcoming trials to determine comparative effectiveness will be discussed.

A systematic review of salvage focal therapies for localised non-metastatic radiorecurrent prostate cancer.

Although radiotherapy to the prostate for cancer is effective, recurrence occurs in 10–15% within 5 years. Traditional salvage treatments for men with radiorecurrent prostate cancer comprise of watchful waiting (WW) with or without androgen deprivation therapy (ADT) or radical prostatectomy (RP). Neither strategy provides ideal therapeutic ratios. Salvage focal ablation is an emerging option. We performed a systematic review of the Medline and Embase databases for studies reporting outcomes of focal salvage brachytherapy (sBT), cryotherapy (sCT) or high-intensity focused ultrasound (sHIFU) for radiorecurrent prostate cancer (conception to April 2019). Results were screened for inclusion against predetermined eligibility criteria. Certain data were extracted, including rates of biochemical disease-free survival (BDFS), metastasis, conversion to second-line therapies and adverse events. Of a total 134 articles returned from the search, 15 studies (14 case series and 1 comparative study) reported outcomes after focal sBT [5], sCT [7] and sHIFU [3]. Cohort size varied depending on intervention, with eligible studies of sBT being small case series. Median follow-up ranged from 10 to 56 months. Although pre-salvage demographics were similar [median age range, 61–75 years; prostate-specific antigen (PSA) range, 2.8–5.5 ng/mL], there was heterogeneity in patient selection, individual treatment protocols and outcome reporting. At 3 years, BDFS ranged from 61% to 71.4% after sBT, 48.1–72.4% after sCT and 48% after sHIFU. Only studies of sCT reported 5-year BDFS, which ranged from 46.5% to 54.4%. Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies (although this was poorly reported). Grade 3 adverse events were rare. This systematic review indicates that salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated. Unfortunately, there is heterogeneity in the study design of existing evidence. Level 1 research comparing salvage focal therapies to existing whole-gland strategies is needed to further establish the role of these promising treatments.

Atypical central neurocytoma with leptomeningeal dissemination: a case report

BackgroundCentral neurocytomas represent 0.25–0.5% of all intracranial tumors in adults. Leptomeningeal spread is uncommon, and the exact incidence of meningeal spread is unknown due to sparse literature. We present the clinical course and management outcome of a case of atypical central neurocytoma with leptomeningeal spread.Case presentationA young gentleman, who initially presented with memory loss, was found to have a right intra-axial periventricular mass on imaging. He underwent subtotal resection, and operative histopathology suggested a periventricular atypical neurocytoma. In view of subtotal resection, adjuvant focal radiation therapy was recommended, but he developed headache and blurring of vision 10 days postoperatively. Contrast enhanced craniospinal magnetic resonance imaging (MRI) showed residual primary tumor as well as diffuse leptomeningeal spread. Cerebrospinal fluid cytology also showed malignant cells. After tumor board discussion, craniospinal axis irradiation was advised and delivered. He remained disease-free for 10 months after radiation therapy, but then developed local and spinal recurrence, and offered salvage chemotherapy. His general condition deteriorated following chemotherapy with disease progression, and he was subsequently advised best supportive care.ConclusionLeptomeningeal dissemination in atypical neurocytomas portends an aggressive course and adverse prognosis; management decisions may need tailoring as per individual presentation.

Magnetic resonance imaging of the prostate after focal therapy with high-intensity focused ultrasound.

For clinically significant, locally confined prostate cancer, whole-gland radical prostatectomy and radiotherapy are established effective treatment strategies that, however, come at a cost of significant morbidity related to urinary and sexual side effects. The concept of risk stratification paired with a better understanding of prognostic factors has led to the development of alternative management options including active surveillance and focal therapy for appropriately selected patients with localized disease. High-intensity focused ultrasound (HIFU) is one such minimally invasive, image-guided treatment option for prostate cancer. Due to the relative novelty of HIFU and the increased use of magnetic resonance imaging in prostate cancer, many radiologists are not yet familiar with imaging findings related to HIFU, their temporal evolution as well as imaging appearance of recurrent disease after this type of focal therapy. HIFU induces sharply demarcated, localized coagulative necrosis of a tumor through thermal energy delivered via an endorectalor transurethral ultrasound transducer. In this pictorial review, we aim at providing relevant background information that will guide the reader through the general principles of HIFU in the prostate, as well as demonstrate the imaging appearance of expected post-HIFU changes versus recurrent tumor.

Current state of image-guided focal therapy for prostate cancer

To review the current evidence regarding protocols and outcomes of image-guided focal therapy (FT) for prostate cancer (PCa). A literature search of the latest published studies assessing primary FT for PCa was carried out in Medline and Cochrane library databases followed by a critical review. FT modalities, follow-up strategies, and oncological and toxicity outcomes were summarized and discussed in this review. Twenty-four studies with six different sources of energy met the inclusion criteria. A heterogeneity of patient selection, energy sources, treatment templates, and definitions of failure was found among the studies. While a third of patients may be found to have additional cancer burden over 3-5 years following FT, most patients will remain free of a radical procedure. The vast majority of patients maintain urinary continence and good erectile function after FT. Acute urinary retention is the most common complication, whilst severe complications remain rare. An increasing number of prospective studies with longer follow-up have been recently published. Acceptable cancer control and low treatment toxicity after FT have been consistently reported. Follow-up imaging and routine biopsy must be encouraged post-FT. While there is no reliable PSA threshold to predict failure after FT, reporting post-FT positive biopsies and retreatment rates appear to be standard when assessing treatment efficacy.

Oncological outcomes of 356 patients undergoing salvage focal ablative HIFU or cryotherapy following radiation failure.

5582 Background: Patients that have previously failed radiotherapy for prostate cancer is usually limited to systemic therapy due to morbidity from salvage prostatectomy. We reviewed the outcomes following focal salvage ablative therapy with HIFU or cryotherapy within the UK’s HEAT and ICE registries. Methods: 356 consecutive patients underwent focal ablative treatment after initial radiation treatment failure (28/1/2004-1/10/2019, 194 (54.5%) underwent HIFU (posterior recurrence) and 162 (45.5%) underwent cryotherapy (mostly anterior or T3b). Primary outcome was failure-free survival (FFS) defined as no systemic therapy, whole-gland treatment, metastases or prostate cancer-specific death. Secondary outcomes were adverse events and overall survival. Results: Median (IQR) age was 69years (65-73) and PSA (IQR) was 4.0ng/ml (1-7-7.2). Overall median (IQR) follow-up was 41.3 months (21.4-58.5). Quadrant ablation was performed in 128 (36.0%), hemi-ablation performed in 64 (18.0%), hockey-stick in 5 (1.4%) and 159 (43.8%) had unknown ablative patterns. Due to histological or MRI proven recurrence/residual disease, 31 (8.7%) underwent further focal salvage re-treatment. FFS (95%CI) at 3 and 6 years were 81% (76-87%) and 75% (68-83%) respectively. Median (IQR) time to failure was 15.5 months (19.7). Overall survival (95%CI) at 3 and 6 years were 97% (95-100%) and 88% (81-96%) respectively. Prostate-specific mortality was 2.8%. Overall 3 (0.8%) patients were managed for fistula formation, 16 (4.5%) were treated for UTIs. Conclusions: Salvage focal ablative therapy for radio-recurrent prostate cancer is safe and provides good short to medium-term oncological control. The FORECAST study is awaited to further determine oncological outcomes in this cohort.