Focal Therapy Research Articles

Role of focal laser retinal photocoagulation in treatment of diabetic macular edema

Vascular endothelial growth factor (anti-VEGF) inhibitors in action have demonstrated efficacy and safety in the treatment of diabetic macular edema (DME), and have changed both the goal and prospects for treatment of this disease. Consequently, the role of focal laser retinal photocoagulation in the treatment of DME has been actively debated. However, technical advances in new laser systems, treatment protocols for anti-VEGF drug research, and the functional impact of modern focal photocoagulation are necessary to assess the role of laser coagulation in the treatment of DME. A wide range of clinical studies of laser therapy was necessary as an additional treatment for 20 to 50 % of patients receiving monotherapy with anti-VEGF drugs in patients with diabetic macular edema. In addition, a lower frequency of repeated treatment and a more stable reduction in retinal thickness have been demonstrated in other studies. However, the lack of information about the laser systems used, their technical characteristics, and application protocols often make it difficult to compare directly the results of anti-VEGF tests. Therefore, the aim of our work was to analyze the currently available data related to the potential role of focal laser photocoagulation in the treatment of DME, including a detailed review of the most commonly used laser systems. The results obtained with sub-threshold diode micro-pulse laser photocoagulation may be a valuable option as an adjunct therapy to treatment with angiogenesis inhibitors. Current evidence suggests that focal laser therapy should still exist as an adjunct therapy for many patients.

Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?

ObjectivesTo evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer.Patients and MethodsWe identified men who underwent primary radical prostatectomy for organ‐ confined prostate cancer over a 3‐year period. Cancer foci on whole‐mount histology were marked out, coding low‐grade (LG; Gleason 3) and high‐grade (HG; Gleason 4–5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT.ResultsThere were 122 MRI‐detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5–6 mm for FT. For tumours ≤12 mm in diameter, applying 5‐ and 6‐mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components.ConclusionsMultiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.

Current and Emerging Clinical Applications of PSMA PET Diagnostic Imaging for Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells, and several PSMA ligands for PET imaging are now available worldwide. 68Ga-PSMA-11 has already received U.S. Food and Drug Administration and European Medicines Agency approval, and use of PSMA PET is currently suggested by several international guidelines for investigating PCa in different clinical settings. In primary PCa, PSMA PET has been shown to be superior to cross-sectional imaging for the detection of pelvic lymph nodes and distant metastases with subsequent clinical management changes. Additionally, it might also have a role in intraprostatic tumor localization, especially when combined with multiparametric MRI. In a setting of PCa recurrence, higher detection rates have been observed than for any other available imaging techniques, especially at low prostate-specific antigen values. Furthermore, PSMA PET consistently led to a shift in clinical management, thus increasing the proportion of radiotherapy, surgery, or other focal therapies at the expense of systemic options or no treatment. In oligometastatic disease after radical surgery, PSMA PET may be relevant in guiding a metastasis-directed therapy approach, as preliminary data seem to suggest a benefit in terms of progression-free survival after treatment of PSMA PET-positive lesions. As a staging and gatekeeping technique, PSMA PET represents a reliable whole-body imaging procedure in combination with second-line therapy of castration-resistant PCa, as well as being pivotal when assessing patients eligible for radioligand therapy such as 177Lu-PSMA. This critical review aims at providing a comprehensive overview of the latest literature on the current or emerging main indications, as well as a general outlook on the recommended interpretation criteria for PSMA PET imaging.

Significant Impact of the Anterior Transition Zone Portion Treatment on Urinary Function After Focal Therapy with High-Intensity Focused Ultrasound for Prostate Cancer.

Background: There is lack of evaluation of the effect of the treated area on the urinary function after focal therapy. The objectives of the study is to evaluate the effects of focal therapy on urinary function in the anterior portion of the transition zone (TZ) with transrectal high-intensity focused ultrasound (HIFU) for localized prostate cancer (PCa). Methods: From 2016 to 2018, patients who were diagnosed as having localized PCa and treated with focal therapy with HIFU, were included prospectively. The urinary function and complications were evaluated separately in the treated regions of the anterior TZ (TZ group) and other portions (other group) for 12 months. Before and after the treatment, the International Prostate Symptom Score (IPSS), IPSS Quality Of Life (QOL), Overactive Bladder Symptom Score (OABSS), and uroflowmetry were evaluated to assess the urinary function. Results: Ninety patients were included in the study. There was no significant differences in the patients' characteristics between the two groups. At 1 month after the treatment, IPSS (p = 0.011), IPSS QOL (p = 0.002), OABSS (p = 0.002), maximum flow rates (p = 0.011), and residual urine volume (p = 0.011) in TZ group were significantly deteriorated compared with the other group. Multivariate logistic regression analysis revealed that anterior TZ treatment (odds ratio, 3.386; p = 0.029) was an independent risk factor for the deterioration with ≥32% of preoperative status of maximum flow rates. Concerning complication, the rates of Grade 2 urinary retention and Grade 3 urethral stricture were 15.4% and 11.5% in the TZ group and 0% and 0% in the other group, respectively. Conclusions: There was a greater risk of urinary dysfunction with treatment in the anterior TZ portion than in the other portion at 1 month after focal therapy with HIFU.

Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: Recommendations of an international Delphi consensus

BackgroundWith the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS). MethodsA 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement. ResultsFifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community. ConclusionsFT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.

Magnetic resonance image–guided focused ultrasound robotic system for transrectal prostate cancer therapy

BackgroundA magnetic resonance image (MRI) guided robotic device for focussed ultrasound therapy of prostate cancer (PC) was developed. The device offers movement in 5 degrees of freedom (DOF) and uses a single‐element transducer that operates at 3.2 MHz, has a diameter of 25 mm and focuses at 45 mm.MethodsThe MRI compatibility of the system was evaluated in a 1.5 T scanner. The ability of the transducer to create lesions was evaluated in laboratory and MRI settings, on ex vivo pork tissue and in vivo rabbit thigh tissue.ResultsCavitational and thermal lesions were created on the excised pork tissue. In vivo experiments proved the efficacy of the system in ablating muscle tissue without damaging intervening areas.ConclusionsThe MRI compatible robotic system can be placed on the table of any commercial MRI scanner up to 7 T. The device has the ability of future use for transrectal focal therapy of PC with the patient in supine position.

Molecular imaging of orthotopic prostate cancer with nanobubble ultrasound contrast agents targeted to PSMA

Ultrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice. Our results demonstrated that PSMA-targeted NBs had increased extravasation and retention in PSMA-expressing orthotopic mouse tumors. These processes are reflected in significantly different time intensity curve (TIC) and several kinetic parameters for targeted versus non-targeted NBs or LUMASON MBs. These, may in turn, lead to improved image-based detection and diagnosis of PCa in the future.

New frontiers in focal therapy for prostate cancer: Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging.

Imaging has a central role in the context of focal therapy (FT) for prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET. Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios. Limited evidence on PSMA PET/MRI is available in the setting of FT. PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa. PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence. The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography. PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT. Further studies are needed to confirm its applications in this specific clinical setting.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases

PurposePredicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). Methods and MaterialsWe prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. ResultsPatients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. ConclusionsThese data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Abstract PD13-06: Incidence and management of central nervous system metastases in patients with inflammatory breast cancer

Abstract Background: Patients (pts) with inflammatory breast cancer (IBC) have a high risk of central nervous system (CNS) metastasis (mets) with their associated impact on longevity and quality of life. Given evolving CNS-directed treatments, including focal radiation (RT), we compared the proportion of pts diagnosed with asymptomatic CNS mets before and after 2012 as data from Phase III trials in the preceding years (yr) increasingly supported the use of stereotactic radiosurgery (SRS). Specific attention was paid to pts treated with tri-modality therapy (TMT), defined as preoperative systemic therapy, surgery, and RT to determine whether screening for asymptomatic CNS mets would be beneficial. Methods: We retrospectively reviewed the records of pts diagnosed with IBC 1997-2019 and enrolled in an IRB-approved registry at a dedicated IBC center. CNS met-free survival time was defined as the time from IBC diagnosis to date of CNS mets. Alive CNS met-free pts were censored at their latest survival date and death was treated as a competing risk. Cumulative CNS mets incidence was computed. Analyses were stratified based on stage at diagnosis (III vs. de novo IV) and receipt of TMT. For pts completing TMT, the completion date was the starting point for cumulative incidence calculations. Overall survival (OS) was estimated as the time from CNS mets diagnosis to death, with censoring for pts who were still alive. Results: A total of 531 pts were identified; 372 (70%) with stage III; 159 (30%) with de novo Stage IV disease. The median follow-up for pts presenting with stage III and stage IV disease at diagnosis was 5.6 yr and 1.8 yr, respectively. 124 pts had CNS mets; 5 of them at diagnosis. CNS was the first site of mets or progression in 50 pts (9.4%). The cumulative incidence of CNS mets stratified by stage at diagnosis and receipt of TMT is seen in Table 1. Among the 50 de novo Stage IV pts who completed TMT, 4 developed CNS mets prior to surgery. The median overall survival (mOS) after CNS mets was 0.6 yr (IQR: 0.2 - 1.4). Results stratified by tumor subtype were: HER2+ disease (n=51) 1.4 yr (IQR: 0.6 - 3.7); hormone receptor+/HER2- (n=27) 0.6 yr (IQR: 0.2 - 1.2); triple negative (n=40) 0.2 yr (IQR: 0.1 - 0.5). Most pts with CNS mets (87/124, 70%) had neurologic symptoms prompting imaging. There was no difference in the proportion of asymptomatic pts diagnosed with CNS mets prior to or after 2012. Management of CNS mets was as follows: 47 pts (38%) received whole brain RT (WBRT) alone, 22 (18%) SRS alone, 15 WBRT + SRS (12%), 6 resection + WBRT (5%), and 5 resection + SRS (4%). The remaining pts received several of these modalities with or without intrathecal chemotherapy (13, 11%) or CNS treatment was not documented (16, 13%). A total of 258/531 pts have died (49%). Of these pts, 103 (40%) had CNS mets. 67/103 (65%) died due to CNS mets. Conclusions: Among pts with IBC completing TMT, the incidence of CNS mets is as high as 20% both in de novo Stage IV pts at 1 yr and in Stage III pts within 5 yrs, supporting routine surveillance brain MRI among pt with Stage IV disease. The majority of pts continue to receive WBRT with its resultant toxicities. Efforts should be made to identify CNS mets early to facilitate more focal therapy. Future research on systemic therapy with CNS penetrance for IBC patients should be pursued. These data support an ongoing prospective study of screening brain MRI in pts with Stage III IBC to quantify the incidence of CNS mets, utilization of WBRT and impact on neurologic quality of life (NCT04030507). Cumulative Incidence of CNS MetsNo.1 year (95% CI)2 year (95% CI)3 year (95% CI)Stage III (All)3725% (3-7)9% (6-12)18% (14-23)Stage IV (All)15417% (12-24)30% (22-37)42% (32-51)Stage III (TMT)3045% (3-8)11% (8-16)19% (14-24)Stage IV (TMT)4621% (10-34)28% (16-43)35% (20-50) Citation Format: Laura Warren, Samuel M Niman, Marie Claire Remolano, Jean Landry, Faina Nakhlis, Jennifer R Bellon, Meredith M Regan, Beth A Overmoyer. Incidence and management of central nervous system metastases in patients with inflammatory breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-06.

Defining the index lesion for potential salvage partial or hemi-gland ablation after radiation therapy for localized prostate cancer

BackgroundSalvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. ObjectiveTo evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens. Design, setting, and participantsMen who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis. Outcome measurements and statistical analysisPrimary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides. Results and limitationsOf 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%–89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men. ConclusionsIn men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.

Treatment of small and medium retinoblastoma tumors with Iris diode laser

Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report the functional and anatomical outcomes for small and medium retinoblastomas treated with focal laser therapy with or without systemic chemotherapy. A retrospective case study was conducted including pediatric patients with macular retinoblastoma treated with systemic chemotherapy and laser ablation from July 1990 to July 2015 at Washington University School of Medicine/Saint Louis Children's Hospital. Fourteen eyes (11 patients) with small and medium retinoblastoma tumors were treated with repetitive indirect laser hyperthermia and seven of those patients were treated with systemic chemotherapy as well. Using the International Retinoblastoma classification, one eye was stage A, 10 eyes were stage B, and three eyes were stage C. The mean follow-up time was 7.7 years. There were no recurrences of tumor in the patients. Final visual acuity outcomes were 20/20 to 20/50 in four eyes, 20/60 to 20/200 in four eyes, and 20/400 or less in six eyes. None of the patients developed metastatic disease. The evidence for systemic chemotherapy and diode laser therapy is limited to case series and retrospective reviews, but evidence suggests that it is an effective treatment for small and medium sized retinoblastoma tumors involving the macula with the potential for good visual outcomes.

Multifunctional nanostructured drug delivery carriers for cancer therapy: Multimodal imaging and ultrasound-induced drug release

Development of multimodal systems for therapy and diagnosis of neoplastic diseases is an unmet need in oncology. The possibility of simultaneous diagnostics, monitoring, and therapy of various diseases allows expanding the applicability of modern systems for drug delivery. We have developed hybrid particles based on biocompatible polymers containing magnetic nanoparticles (MNPs), photoacoustic (MNPs), fluorescent (Cy5 or Cy7 dyes), and therapeutic components (doxorubicin). To achieve high loading efficiency of MNP and Dox to nanostructured carriers, we utilized a novel freezing-induced loading technique. To reduce the systemic toxicity of antitumor drugs and increase their therapeutic efficacy, we can use targeted delivery followed by the remote control of drug release using high intensity-focused ultrasound (HIFU). Loading of MNPs allowed performing magnetic targeting of the carriers and enhanced optoacoustic signal after controlled destruction of the shell and release of therapeutics as well as MRI imaging. The raster scanning optoacoustic mesoscopy (PA, RSOM), MRI, and fluorescent tomography (FT) confirmed the ultrasound-induced release of doxorubicin from capsules: in vitro (in tubes and pieces of meat) and in vivo (after delivery to the liver). Disruption of capsules results in a significant increase of doxorubicin and Cy7 fluorescence initially quenched by magnetite nanoparticles that can be used for real-time monitoring of drug release in vivo. In addition, we explicitly studied cytotoxicity, intracellular localization, and biodistribution of these particles. Elaborated drug delivery carriers have a good perspective for simultaneous imaging and focal therapy of different cancer types, including liver cancer.

Robust Resolution-Enhanced Prostate Segmentation in Magnetic Resonance and Ultrasound Images through Convolutional Neural Networks

Prostate segmentations are required for an ever-increasing number of medical applications, such as image-based lesion detection, fusion-guided biopsy and focal therapies. However, obtaining accurate segmentations is laborious, requires expertise and, even then, the inter-observer variability remains high. In this paper, a robust, accurate and generalizable model for Magnetic Resonance (MR) and three-dimensional (3D) Ultrasound (US) prostate image segmentation is proposed. It uses a densenet-resnet-based Convolutional Neural Network (CNN) combined with techniques such as deep supervision, checkpoint ensembling and Neural Resolution Enhancement. The MR prostate segmentation model was trained with five challenging and heterogeneous MR prostate datasets (and two US datasets), with segmentations from many different experts with varying segmentation criteria. The model achieves a consistently strong performance in all datasets independently (mean Dice Similarity Coefficient -DSC- above 0.91 for all datasets except for one), outperforming the inter-expert variability significantly in MR (mean DSC of 0.9099 vs. 0.8794). When evaluated on the publicly available Promise12 challenge dataset, it attains a similar performance to the best entries. In summary, the model has the potential of having a significant impact on current prostate procedures, undercutting, and even eliminating, the need of manual segmentations through improvements in terms of robustness, generalizability and output resolution.

Focal Brachytherapy for Localized Prostate Cancer: Midterm Outcomes

PurposeFocal brachytherapy (F-BT) is a suitable technique for focal therapy in localized prostate cancer. It has the ability to adapt the seed implantation to the volume and location of the tumor. The aim of this study was to assess F-BT oncologic, functional, and toxicity midterm outcomes in men who underwent prostate cancer treatment. Methods and MaterialsThe study included 39 men with low- to intermediate-risk prostate cancer treated with F-BT between 2010 and 2015. The dose prescription was 145 Gy. Failure was defined as the presence of any residual prostate cancer in the treated area. The primary and secondary endpoints were the F-BT oncologic and functional outcomes, respectively. A 2-sided P value < .05 indicated statistical significance. ResultsThe mean follow-up time was 65 months (range, 43-104 months). After 24 months, 34 patients underwent control biopsies and 5 patients refused. The biopsies were negative in 27 cases (79%) and positive in 7 cases (21%), all outside the volume treated. Biochemical relapse-free survival at 5 years, disease-free survival, and overall survival were 96.8% ± 0.032%, 79.5% ± 0.076%, and 100%, respectively. The mean International Prostate Symptom Score at 2 months was significantly higher than initially (P = .0003), with no significant difference later. No late urinary, sexual, or rectal toxicity was observed. Salvage treatment was possible with good tolerance at 3.4 years of follow-up. Limitations of this study include the retrospective nature and lack of randomization. ConclusionsF-BT is a safe and effective treatment for selected patients presenting with low- or intermediate-risk localized prostate cancer.

Making a case "for" focal therapy of the prostate in intermediate risk prostate cancer: current perspective and ongoing trials.

Focal therapy is growing as an alternative management options for men with clinically localized prostate cancer. Parallel to the increasing popularity of active surveillance (AS) as a treatment for low-risk disease, there has been an increased interest towards providing focal therapy for patients with intermediate-risk disease. Focal therapy can act as a logical "middle ground" in patients who seek treatment while minimizing potential side effects of definitive whole-gland treatment. The aim of the current review is to define the rationale of focal therapy in patients with intermediate-risk prostate cancer and highlight the importance of patient selection in focal therapy candidacy.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society

Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa.A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold.Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority.The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Current evidence for focal therapy and partial gland ablation for organ-confined prostate cancer: systematic review of literature published in the last 2 years.

The shift in the diagnostic algorithm for prostate cancer to early imaging with mpMRI has resulted in many patients being diagnosed with small volume, apparently unilateral, clinically significant cancers. In these patients, a minimally invasive, nonmorbid intervention is appealing. The aim of this study was to review data reported within the last 2 years on focal therapy and partial gland ablation for organ-confined prostate cancer. High-intensity focal ultrasound, focal cryotherapy, photodynamic therapy, irreversible electroporation and focal laser ablation, have been used as treatment modalities for localized prostate cancer treatment. The reported oncologic outcomes vary widely and makes comparisons challenging. All the focal therapies report low rates of complications, and high rates of continence and erectile function preservation. The most common adverse events are hematuria, urinary retention and urinary tract infections. During this period, the initial results of several new technologies including MRI-guided transurethral ultrasound ablation were published. Focal therapy and partial gland ablation for organ-confined prostate cancer is an option for patients with intermediate-risk disease because of its low complication profile and preservation of QOL. Trials comparing the outcome of different focal therapy technologies have not been carried out, and the existing evidence does not point to one approach being clearly superior to others. Long-term oncologic outcome is lacking. Despite this, for men with unilateral intermediate-risk prostate cancer whose disease is often relatively indolent, focal therapy is an appealing option.

This Month in Adult Urology

This Month in Adult Urology

Focal Ablation Therapies in Prostate Cancer

Focal ablation therapies in prostate cancer have been actively evaluated in the light of recent literature. According to published data,focal ablation therapies appear to be well tolerated and have an acceptable side effect profile. Moreover, while clinical outcomes were not homogenous, short-term oncological results of some focal ablation therapies such as laser and irreversible electroporation (IRE) have been found as good as curative ones. While waiting long-term oncological results, focal ablation therapies in prostate cancer are beinmg used increasingly.