Corrigendum to "Surveillance one year post focal cryotherapy for clinically significant prostate cancer using mpMRI and PIRADS v2.1: An initial experience from a prospective phase II mandatory biopsy study" [Eur. J. Radiol. Open 11 (2023) 100529].

[This corrects the article DOI: 10.1016/j.ejro.2023.100529.].

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes. METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients. CONCLUSION: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

The individualized delineation of clinical target volume for primary nasopharyngeal carcinoma based on invasion risk of substructures: A prospective, real-world study with a large population.

BACKGROUND AND PURPOSE: The delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. MATERIALS AND METHODS: We preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 âˆ¼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. RESULTS: From January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1-126.9) and 51.4 (39.5-78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5-98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. CONCLUSION: Our individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.

Embracing Personalized Strategies in Radiotherapy for Nasopharyngeal Carcinoma: Beyond the Conventional Bounds of Fields and Borders.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TN-stages. Locoregional control rates have been impressive even from the 2D radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there has been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and the delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

Longitudinal post-radiotherapy plasma Epstein-Barr virus DNA trends inform on optimal risk stratification in endemic nasopharyngeal carcinoma.

OBJECTIVES: To characterize longitudinal changes in Epstein-Barr virus (EBV) DNA post-radiotherapy in nasopharyngeal carcinoma (NPC) patients, and investigate whether an early (0-2 weeks) or delayed (8-12 weeks) EBV DNA result better predicts for disease-free survival (DFS). MATERIALS AND METHODS: Histologically-confirmed NPC patients with ≥1 EBV DNA test quantified using the harmonized BamHI-W polymerase chain reaction-based assay at 0-2 and 8-12 weeks post-radiotherapy were included. RESULTS: We identified 302 patients with EBV DNA measured at 0-2 weeks post-radiotherapy; of which, 110 (36.4 %) underwent a repeat test at 8-12 weeks post-treatment. Patients harboring a detectable EBV DNA at 0-2 weeks experienced an inferior DFS (adjusted HR1-264 copies 1.72 [95 %CI: 1.05-2.83], P = 0.031; AHR≥265 copies 4.39 [95 %CI: 1.68-11.44], P = 0.002 relative to 0 copies/mL). At 8-12 weeks, we observed substantial shifts in EBV DNA readings from 0 to 2 weeks; 76/110 (69.1 %) and 34/110 (30.9 %) patients at 0-2 weeks versus 90/110 (81.8 %) and 20/110 (18.2 %) at 8-12 weeks recorded undetectable and detectable EBV DNA, respectively. Positive EBV DNA at 8-12 weeks was strongly associated with relapse (73.3 % [11/15] for 1-264; 80.0 % [4/5] for ≥265 subgroups had relapses versus 15.6 % [14/90] for 0 copies/mL). Area under receiver operating curve values for 2-year relapse rates were 0.817 (95 %CI: 0.725-0.909) for stage + EBV DNA8-12w versus 0.654 (95 %CI: 0.542-0.765) for stage + EBV DNA0-2w. CONCLUSION: EBV DNA is dynamic post-radiotherapy, and delayed EBV DNA testing better enriched for higher-risk NPC patients. This implicates trials investigating adjuvant chemotherapy intensification based on early EBV DNA testing.

Cluster-based radiomics reveal spatial heterogeneity of bevacizumab response for treatment of radiotherapy-induced cerebral necrosis.

Background: Bevacizumab is used in the treatment of radiation necrosis (RN), which is a debilitating toxicity following head and neck radiotherapy. However, there is no biomarker to predict if a patient would respond to bevacizumab. Purpose: We aimed to develop a cluster-based radiomics approach to characterize the spatial heterogeneity of RN and map their responses to bevacizumab. Methods: 118 consecutive nasopharyngeal carcinoma patients diagnosed with RN were enrolled. We divided 152 lesions from the patients into 101 for training, and 51 for validation. We extracted voxel-level radiomics features from each lesion segmented on T1-weighted+contrast and T2 FLAIR sequences of pre- and post-bevacizumab magnetic resonance images, followed by a three-step analysis involving individual- and population-level clustering, before delta-radiomics to derive five radiomics clusters within the lesions. We tested the association of each cluster with response to bevacizumab and developed a clinico-radiomics model using clinical predictors and cluster-specific features. Results: 71 (70.3%) and 34 (66.7%) lesions had responded to bevacizumab in the training and validation datasets, respectively. Two radiomics clusters were spatially mapped to the edema region, and the volume changes were significantly associated with bevacizumab response (OR:11.12 [95% CI: 2.54-73.47], P = 0.004; and 1.63[1.07-2.78], P = 0.042). The combined clinico-radiomics model based on textural features extracted from the most significant cluster improved the prediction of bevacizumab response, compared with a clinical-only model (AUC:0.755 [0.645-0.865] to 0.852 [0.764-0.940], training; 0.708 [0.554-0.861] to 0.816 [0.699-0.933], validation). Conclusion: Our radiomics approach yielded intralesional resolution, enabling a more refined feature selection for predicting bevacizumab efficacy in the treatment of RN.

Assessing the efficacy of palliative radiation treatment schemes for locally advanced squamous cell carcinoma of the head and neck: a meta-analysis.

Background: The objective to assess the outcomes from different palliative radiotherapy (RT) schedules in incurable head and neck cancer (HNC), to evaluate if there is a relationship between RT dose, technique, and fractionation with tumor response in contrast to the occurrence of adverse effects. Materials and methods: Eligible studies were identified on Medline, Embase, the Cochrane Library, and annual meetings proceedings through June 2020. Following PRISMA and MOOSE guidelines, a cumulative meta-analysis of studies for overall response rate (ORR), overall survival (OS), progression-free survival (PFS), pain/dysphagia relief, and toxicity was performed. A meta-regression analysis was done to assess if there is a connection between RT dose, schedule, and technique with ORR. Results: Twenty-eight studies with 1,986 patients treated with palliative RT due to incurable HNC were included. The median OS was 6.5 months [95% confidence interval (CI): 5.6-7.4], and PFS was 3.6 months (95% CI: 2.7-4.3). The ORR, pain and dysphagia relief rates were 72% (95% CI: 0.6-0.8), 83% (95% CI: 52-100%), and 75% (95% CI: 52-100%), respectively. Conventional radiotherapy (2D-RT) or conformational radiotherapy (3D-RT) use were significantly associated with a higher acute toxicity rate (grade ≥ 3) than intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). On meta-regression analyses, the total biological effective doses (BED) of RT (p = 0.001), BED > 60 Gy10 (p = 0.001), short course (p = 0.01) and SBRT (p = 0.02) were associated with a superior ORR. Conclusions: Palliative RT achieves tumor response and symptom relief in incurable HNC patients. Short course RT of BED > 60 Gy using IMRT could improve its therapeutic ratio. SBRT should be considered when available.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients - a national cancer centre experience.

Purpose or objective: The COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery. Materials and methods: In this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel. Results: Significantly, there was a reduction of 37-46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines. Conclusion: We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient's confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

Challenges and Opportunities With the Use of Hypofractionated Radiation Therapy in Cancer Care: Regional Perspectives From South Korea, Japan, Singapore, and Australia.

Hypofractionated radiotherapy schedules provide higher per-fraction radiation doses delivered in fewer fractions than conventional schedules. This novel delivery method is supported by a large body of clinical trial evidence across various cancer sites in both curative and palliative settings. Hypofractionation is associated with benefits such as lower costs, improved patient access and increased treatment precision, which has led to its inclusion in various treatment guidelines. Despite this, utilization is not uniform across cancer sites and geographic regions due to reasons such as reimbursement models, nuances in healthcare systems, and professional culture. Key factors to ensure patients benefit from access to high quality radiotherapy include publishing clinical evidence, cross-country collaboration to fill knowledge gaps, reviewing reimbursement models, and improving patient advocacy in treatment decision-making.

The influence of the "cancer" label on perceptions and management decisions for low-grade prostate cancer.

BACKGROUND: Grade Group 1 (GG1) prostate cancer should be managed with active surveillance (AS). Global uptake of AS remains disappointingly slow and heterogeneous. Removal of cancer labels has been proposed to reduce GG1 overtreatment. We sought to determine the impact of GG1 disease terminology on individual's perceptions and decision making. METHODS: Discrete choice experiments were conducted on 3 cohorts: healthy men, canonical partners (partners), and patients with GG1 (patients). Participants reported preferences in a series of vignettes with 2 scenarios each, permuting key opinion leader-endorsed descriptors: biopsy (adenocarcinoma, acinar neoplasm, prostatic acinar neoplasm of low malignant potential [PAN-LMP], prostatic acinar neoplasm of uncertain malignant potential), disease (cancer, neoplasm, tumor, growth), management decision (treatment, AS), and recurrence risk (6%, 3%, 1%, <1%). Influence on scenario selection were estimated by conditional logit models and marginal rates of substitution. Two additional validation vignettes with scenarios portraying identical descriptors except the management options were embedded into the discrete choice experiments. RESULTS: Across cohorts (194 healthy men, 159 partners, and 159 patients), noncancer labels PAN-LMP or prostatic acinar neoplasm of uncertain malignant potential and neoplasm, tumor, or growth were favored over adenocarcinoma and cancer (P < .01), respectively. Switching adenocarcinoma and cancer labels to PAN-LMP and growth, respectively, increased AS choice by up to 17%: healthy men (15%, 95% confidence interval [CI] = 10% to 20%, from 76% to 91%, P < .001), partners (17%, 95% CI = 12% to 24%, from 65% to 82%, P < .001), and patients (7%, 95% CI = 4% to 12%, from 75% to 82%, P = .063). The main limitation is the theoretical nature of questions perhaps leading to less realistic choices. CONCLUSIONS: "Cancer" labels negatively affect perceptions and decision making regarding GG1. Relabeling (ie, avoiding word "cancer") increases proclivity for AS and would likely improve public health.

Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma.

Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC.

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study.

BACKGROUND: Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA-NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). METHODS: Patients with biopsy-proven NPC and planned for IC + CCRT were recruited. IC entailed two cycles of 3-weekly docetaxel 75 mg/m2 and cisplatin 75 mg/m2 ; CCRT entailed two to three cycles of 3-weekly cisplatin 100 mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre-IC, post-cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0 ) by the end of treatment (W7-CCRT). Secondary endpoints included body mass index, NRS2002 and PG-SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicities and survivals. The associations between primary and secondary endpoints were also evaluated. RESULTS: One hundred and seventy-one patients were enrolled. Median follow-up was 67.4 (IQR: 64.1-71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4-CCRT (median of 4.0% [IQR: 0.0-7.0%]) and peaked at W7-CCRT (median of 8.5% [IQR: 4.1-11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7-CCRT, which was associated with a higher malnutrition risk (NRS2002 ≥ 3 points: 87.7% [WL ≥ 5.0%] vs 58.7% [WL < 5.0%], P < 0.001) and requirement of nutritional intervention (PG-SGA ≥ 9 points: 82.0% [WL ≥ 5.0%] vs 66.7% [WL < 5.0%], P = 0.038). The median %WL at W7-CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P = 0.025) and xerostomia (9.1% vs 6.3%, P = 0.003). Besides, patients with cumulative WL5.0 also reported a higher detriment on QoL at W7-CCRT compared with patients without, with a difference of -8.3 points (95% CI [-15.1, -1.4], P = 0.019). CONCLUSIONS: We observed a high prevalence of WL among LA-NPC patients who were treated with IC + CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC + CCRT and inform on nutritional intervention strategies.

Patient-reported functional outcomes and oncological control after primary focal cryotherapy for clinically significant prostate cancer: A Phase II mandatory biopsy-monitored study.

INTRODUCTION: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa). METHODS: The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence. RESULTS: Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance. CONCLUSION: FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients.