Low-volume Metastatic Disease Research Articles

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Treatment strategies for borderline resectable pancreatic neuroendocrine tumors: a narrative review.

Well-differentiated pancreatic neuroendocrine tumors (pNETs) are a group of rare, heterogeneous tumors that originate in the endocrine tissue of the pancreas and account for 1-2% of all pancreatic neoplasms. The majority of pNETs are non-functional and typically follow a more indolent course. Especially at early stages, the primary management of pNETs is surgical resection which is associated with relatively low rates of recurrence and excellent long-term prognosis. On the other hand, some patients will present with locally advanced primary tumors or low volume metastatic disease in which complete surgical resection may be more difficult to achieve and recurrence rates are significant. Unlike treatment of borderline resectable (BR) pancreatic adenocarcinoma, in which neoadjuvant treatment strategies are becoming standardized, borderline resectability is not a currently established terminology for pNETs and the optimal multidisciplinary treatment approach is poorly understood. We performed a literature search on PubMed, Google Scholar, and ClinicalTrials.gov using keywords, including 'pancreatic neuroendocrine tumor' and 'borderline resectable'. All studies and review articles in English with full text were considered. Each publication was independently reviewed. We introduce the concept of BR-pNETs, focusing on important criteria that should be included in their definition by balancing the feasibility of resection and the clinical utility of surgery. We suggest that extended resection, involving vascular reconstruction, adjacent organ resection, and/or liver metastasis, should be considered at experienced, high volume centers. Furthermore, we outline multidisciplinary treatment strategies, including systemic and locoregional treatment options, for optimizing outcomes for this growing patient population. Formalizing the definition of resectability in pNETs through multidisciplinary collaborative research will be important for standardizing the indications for multimodality treatment and aggressive surgical approaches for patients.

(O-15) SEXUALITY IN PATIENTS WITH ADVANCED PROSTATE CANCER: A REVIEW

Abstract Introduction Androgen deprivation therapy (ADT) remains the gold standard in treatment of advanced prostate cancer (APC). Disease remission means improved quality of life, mental health, social interactions, in addition to pain reduction. However, most experience a significant drop in sexual desire, reduction in rigidity and duration of erections, and a decrease in the frequency of sexual intercourse. Material and Methods A review of literature on sexuality in patients with APC was carried out. Results The prevalence of sexual dysfunction (SD) in patientes with APC is higher. However, its treatment remains in the background, considering the priority given to oncological treatment. Assessing baseline sexual function before starting ADT, as well as monitoring changes that occur during treatment are important aspects to mitigate negative effects. Individualization of the therapeutic plan allows satisfactory erectile response with oral medications in up to 33% of patients, reaching 80% with the use of combined therapies, such as injections and vacuum devices. Intermittent ADT appears as an interesting option for selected groups of patients with APC, with biochemical recurrence and low-volume metastatic disease, allowing a recovery of sexual function in the intervals without treatment, although recovery of sexual function becomes less pronounced and treatment-free intervals become shorter over time. Conclusions The significant drop observed in sexual health still remains a major challenge in the management of patients with APC. Although physical and psychosocial variables may be involved in the etiology of SD, erectile function remains the main determinant of sexual satisfaction in men undergoing any treatment for prostate cancer. Despite emerging themes have been observed in the literature, such as sexual psychotherapy and the role of physical exercises in mitigating the negative effects of ADT, specific studies in this population are still needed. Financing No conflict.

Does use of apalutamide enhance outcomes in combination with radiotherapy in metastatic hormone-sensitive prostate cancer? A real-world experience from the UK.

73 Background: Management of metastatic prostate cancer has undergone a significant change over the past decade, with the introduction of several novel agents and repurposing of others. Latest update from STAMPEDE trials shown prostate radiotherapy (RT) improves OS, without detriment in QoL in metastatic home sensitive prostate cancer mHSPC along with Docetaxel in those with low volume metastatic disease. There is no published data on impact of radiotherapy to prostate on Apalutamide treated mHSPC patients. Here we report our real-world experience of Apalutamide in mHSPC with radiotherapy. Methods: Patients with mHSPC (N = 266) from 5 UK centres, were treated with Apalutamide (240 mg) and ADT along with radiotherapy to prostate as per treating clinician’s discretion. The primary endpoint was objective rate (ORR) as determined by patients achieving a PSA decline of ≥90% (PSA90) and ≥50% (PSA50) and secondary endpoints included biochemical progression free survival (bPFS) and safety. Results: The median age for the whole cohort was 73.4 years (interquartile range 52 - 91), A total of 11.6% had received prior radical treatment (prostatectomy or radiotherapy for localised disease) and 88.4% had de novo metastatic disease. Median baseline PSA was 47 ng/ml (range 0.4-17100). The proportion of patients PSA90 and PSA50 at 3, 6 and 12 months is shown in the Table. Median PSA nadir was 0.1 ng/ml(rage 0.01- 48.2) and median time to reach nadir was 6 months (range 3-24 months). 13.5% (35) patients were treated with radiotherapy (RT) after at least 3 months (range 3 -6 months) of starting apalutamide. Patients received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) of radiotherapy (68 % vs 32%). Higher number of patients in RT group had achieved PSA90 compared to no radiotherapy cohort (97.14 % vs 87.3%, p =0.15). Patients treated with RT had median post treatment of PSA 0.01 ng/ml compared to 0.1 ng/ml in non RT group (p=0.0062). After median follow up of 8.4 months, proportion of patients shown biochemical progression in RT vs non RT group were 5.7 % vs 15 % respectively (p= 0.04). Patients with de novo metastatic disease have shown poor PSA response and higher chance of progression compared to patients who had initial radical treatment. Radiotherapy was well tolerated, with 17 % adverse events (Radiation Therapy Oncology Group grade 3–4) reported in radiotherapy group. Conclusions: Early experience of using apalutamide and radiotherapy in mHSPC showed improved PSA response and delayed progression. Treatment was well tolerated. Further follow up and clinical trials are needed to understand the impact on overall survival. [Table: see text]

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy.

Prostate cancer (PCa) is the most common noncutaneous malignancy in men. Until recent years, accurate imaging of men with newly diagnosed PCa, or recurrent or low-volume metastatic disease, was limited. Further, therapeutic options for men with advanced, metastatic, castration-resistant disease were increasingly limited as a result of increasing numbers of systemic therapies being combined in the upfront metastatic setting. The advent of urea-based, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) has partially addressed those shortcomings in diagnosis and therapy of PCa. On the diagnostic side, there are multiple pivotal phase III trials with several different agents having demonstrated utility in the initial staging setting, with generally modest sensitivity but very high specificity for determining otherwise-occult pelvic nodal involvement. That latter statistic drives the utility of the scan by allowing imaging interpreters to read with very high sensitivity while maintaining a robust specificity. Other pivotal phase III trials have demonstrated high detection efficiency in patients with biochemical failure, with high positive predictive value at the lesion level, opening up possible new avenues of therapy such as metastasis-directed therapy. Beyond the diagnostic aspects of PSMA-targeted radiotracers, the same urea-based chemical scaffolds can be altered to deliver therapeutic isotopes to PCa cells that express PSMA. To date, one such agent, when combined with best standard-of-care therapy, has demonstrated an ability to improve overall survival, progression-free survival, and freedom from skeletal events relative to best standard-of-care therapy alone in men with metastatic, castration-resistant PCa who are post chemotherapy. Within the current milieu, there are a number of important future directions including the use of artificial intelligence to better leverage diagnostic findings, further medicinal chemistry refinements to the urea-based structure that may allow improved tumor targeting and decreased toxicities, and the incorporation of new radionuclides that may better balance efficacy with toxicities than those nuclides that are available.

Mise au point et stratégies thérapeutiques dans le cancer de la prostate avancé et métastatique

Prostate cancer treatment relies on a multimodal approach based on the patient and disease characteristics. In this regard, imaging plays a crucial role in assessing cancer, whether it is for the initial evaluation or when recurrence occurs. Once it becomes metastatic (either at diagnosis or after curative treatment), castration, whether surgical or medical, used to be the sole treatment for these patients. However, since the introduction of chemotherapy with docetaxel and the emergence of next-generation hormone therapies such as abiraterone, enzalutamide, apalutamide and darolutamide, their survival has been significantly improved. In addition to these systemic treatments comes the possibility of irradiating the prostate tumor in patients with low-volume metastatic disease. After several months or years, these patients inevitably progress to the lethal form of the disease: castration-resistant prostate cancer. In this context, besides docetaxel, abiraterone, and enzalutamide, other treatments are also available, such as cabazitaxel, DNA repair-targeting agents like PARP inhibitors, radium-223, or more recently, Lu-PSMA. In some cases, a combination of treatments may also be considered. The objective of this review is to examine the role of imaging in the initial staging and metastatic recurrence work-up of prostate cancer, as well as the various therapeutic strategies for hormone-sensitive and castration-resistant metastatic prostate cancer.

Identification of a Predictive Genomic Biomarker for Prostate Directed Therapy in Synchronous Low-Volume Metastatic Castration Sensitive Prostate Cancer.

Standard of care management for metastatic castration sensitive prostate cancer (mCSPC) includes androgen deprivation therapy (ADT) with docetaxel or second-generation anti-androgen therapy. Recently, randomized data has demonstrated radiotherapy to the prostate is associated with an improvement in overall survival among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to understand the clinical trajectory of patients with mCSPC. Herein we aim to evaluate a high-risk genomic signature for its ability to predict response to prostate directed therapy (PDT). We performed a single institution retrospective review of men with low-volume mCSPC who underwent next-generation sequencing of their tumor. Patients were classified according to the presence of high-risk (HiRi) mutation including pathogenic mutations in either TP53, ATM, BRCA1/2, or Rb1. Our primary endpoint was to determine the effect of PDT on overall survival (OS) in patients with and without a HiRi mutation. Survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable cox regression. Interaction between HiRi mutation and PDT was evaluated. A total of 101 patients with synchronous low-volume CSPC were included in our analysis with a median follow-up of 44 months. Approximately half of patients were found to have a HiRi pathogenic mutation (48.5%) with TP53 mutations accounting for 75.5% of HiRi mutations. On multivariable cox regression PDT was associated with improvement in OS (HR = 0.37, 95% CI 0.16-0.88; p = 0.03). When stratified by presence of HiRi mutation, PDT was not associated with any clinical outcome. Patients with HiRi mutations demonstrated a median OS of 73 vs 66.8 months (p = 0.28) for no PDT and PDT, respectively. Conversely, patients without a HiRi mutation demonstrated a significant improvement in median OS of 60 vs 105.3 months (p<0.01) for no PDT and PDT, respectively. The p-value for interaction for OS between PDT and HiRi mutation was statistically significant (p<0.01). Here we have identified a high-risk genomic biomarker that appears predictive for response to PDT in men with synchronous low-volume mCSPC. Further work validating these results with prospective randomized data is warranted.

Identification of a Predictive Genomic Biomarker for Prostate-directed Therapy in Synchronous Low-volume Metastatic Castration-sensitive Prostate Cancer

BackgroundStandard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC. ObjectiveTo evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT. Design, setting, and participantsWe performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1. Outcome measurements and statistical analysisThe primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated. Results and limitationsA total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study. ConclusionsHere, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted. Patient summaryIn this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation.

A prospective, multicenter head-to-head comparative study in patients with primary high-risk prostate cancer investigating the bone lesion detection of conventional imaging and 18F-PSMA-PET/CT.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an emerging staging tool for patients with primary high-risk prostate cancer (PCa). Patients with primary metastatic disease are staged using PSMA-PET/CT imaging, while previously published randomized clinical trials relied on conventional imaging (i.e., bone scintigraphy (BS) results. The aim of this study was to compare the ability of bone metastatic lesion detection and changes in staging for 18F-PSMA-PET/CT versus BS in high-risk PCa patients. 79 patients with high-risk PCa were prospectively staged using BS and subsequent 18F-PSMA-PET/CT before initial therapy. Patients who presented with a BS showing no metastases represented Group 1, and patients with a BS showing low-volume disease according to the CHAARTED criteria (<4 bone metastases, no metastases outside vertebral column or pelvis and no visceral metastases) represented Group 2. Metastatic risk group according to CHAARTED and treatment strategies based on both imaging modalities were assessed. A change of CHAARTED risk group was observed in 9/70 (12.8%) of patients in Group 1. In Group 2, a change of risk group was found in 66.7% of patients, due to either upstaging (4/9 patients (44.4%)) and downstaging (2/9 patients (22.2%)). Treatment changes due to use of a different imaging modality occurred in almost 20% of patients. In patients with negative for cancer results on BS, upstaging on 18F-PSMA-PET/CT occurred only infrequently. Moreover, 18F-PSMA-PET/CT resulted in both upstaging and downstaging in a substantial subset of patients with low-volume metastatic disease on BS. Treatment changes occurred in almost 20% of cases depending on imaging results.

Radical surgery for stage IV gallbladder cancers: Treatment strategies in patients with limited metastatic burden.

The present study looked at the role of radical surgery in gallbladder cancers (GBC) with limited metastatic disease. The retrospective observational study was conducted to screen the database from 1st January 2010 to 31st December 2019. Patients of GBC found to have low-volume metastatic disease upon surgical exploration were included. Of the 1,040 patients operated for GBC, 234 patients had low-volume metastatic disease (microscopic disease in station 16b1 node or N2 disease isolated port-site metastases, or low burden peritoneal disease with deposits less than 1 cm, in adjacent omentum or adjacent diaphragm or Morrison's pouch or a solitary discontinuous liver metastasis in adjacent liver parenchyma) detected intraoperative. Of these, 62 patients underwent radical surgery for R-0 metastatic disease followed by systemic therapy, while the remaining 172 patients did not undergo radical surgery and were given palliative systemic chemotherapy. Patients who underwent radical surgery had significantly superior overall survival (19 months versus 12 months, p < 0.01) and superior progression-free survival (10 months versus 5 months, p < 0.01) when compared to the rest. This difference in survival was more significant amongst patients when operated on after neoadjuvant chemotherapy. Regression analysis showed that a sub-group of patients with incidental GBC with limited metastases showed more favorable outcomes with radical surgery. Authors suggest a possible role for radical treatment of advanced GBC with a limited metastatic burden. Neoadjuvant chemotherapy can be used for preferentially selecting patients of favorable disease biology for curative treatment.

High-volume mCRPC is associated with decreased cancer specific survival in patients on second-generation hormone therapy in the post docetaxel setting.

192 Background: In the setting of disease progression of metastatic castrate resistant prostate cancer (mCRPC) on docetaxel, abiraterone acetate (AA) and enzalutamide are two commonly used second line therapies with data demonstrating survival benefits. Less is known about patient specific factors that contribute to success with these therapies. The objective of this study is to improve patient selection for post-docetaxel second generation hormone therapy (AA or enzalutamide) by evaluating whether overall metastatic burden is associated with treatment response in this setting. Methods: By retrospective chart review, patients with mCRPC treated with AA or enzalutamide following docetaxel failure (defined as PSA rise and radiographic progression) were identified. Patients were categorized into low volume and high volume metastatic disease based on the number of pre-treatment metastatic lesions; where low volume disease describes patients with ≤ 5 metastatic lesions (e.g. oligometastatic disease), and high volume disease represents patients with &gt; 5 individual lesions. The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Median follow-up time was 29.5 months. Results: 75 patients were identified and included in our analysis: 39 with high volume metastatic disease, and 36 with low volume metastatic disease. Baseline characteristics of age and pre-treatment ECOG were not statistically different between these groups. Pre-treatment high-volume disease burden was significantly associated with increased risk of radiographic disease progression (HR 4.21, 95%CI 1.97-8.99, p &lt; 0.0001) and cancer specific mortality (HR 5.84, 95% CI 1.58-21.53, p = 0.0026) during treatment with second generation androgen deprivation therapy. Conclusions: High volume metastatic disease burden is associated with significantly increased cancer specific mortality and decreased progression free survival for patients on second line therapy with AA or enzalutamide following docetaxel treatment failure.

Survival advantage of locoregional and systemic therapy in oligometastatic breast cancer: an international retrospective cohort study (OLIGO-BC1).

An international retrospective cohort study was conducted to clarify the survival advantage of combination therapy with locoregional and systemic therapy (ST) in oligometastatic breast cancer (BC). Patients with oligometastatic BC diagnosed from 2007 to 2012 were enrolled in center hospitals in China, Korea and Japan. It was defined as a low-volume metastatic disease at up to five sites and not necessarily in the same organ. Cases with brain, pleural, peritoneal and pericardial metastases were excluded. The primary endpoint was overall survival (OS) from the initial diagnosis of oligometastases. OS was summarized using the Kaplan-Meier method. A multivariable Cox regression model was used to estimate the hazard ratio (HR) for clinicopathological factors. Among 1,295 cases registered from February 2018 to May 2019, 932 remained for analysis after the exclusion of unavailable cases and locoregional recurrence. One metastatic site was found in 400 cases, 2 in 243, 3 in 130, 4 in 86 and 5 in 73. At the median follow-up of 4.5years, 5-year OS was 54.7% and 39.7% for 321 cases in the combination therapy group and 611 cases in the ST group, respectively. An adjusted HR was 0.66 (95% confidence interval: 0.55, 0.79). Some types of ST without chemotherapy alone, younger age, ECOG performance status 0, early-stage BC, non-triple negative subtype, fewer metastatic sites and longer duration of surgery to relapse were significantly favorable prognostic factors. Combination therapy may be considered for longer survival under some conditions in oligometastatic BC.

An insight into metastatic Leydig cell tumors: A case report

Sex cord-stromal tumors comprise approximately 5% of all testicular tumors, while the remainder are of germ cell origin. Leydig cell tumors are the most common subtype of testicular sex cord-stromal tumors and account for 1%–2% of all testicular tumors. Leydig cell tumors are mostly benign but approximately 5%–10% of them have malignant potential. The commonest metastatic sites are regional lymph nodes, lung, liver, and bones. Here, we report a case of late metastatic relapsed Leydig cell disease in a 73-year-old male. The goal of this care report was to better understand manifestation and management of patients with late relapsed Leydig cell tumors and low-volume disease. Patients with metastatic Leydig cell tumors (or sex cord-stromal tumors) have poor prognosis, and standard treatment recommendations do not exist. Surgical resection of metastasis and/or chemotherapy with bleomycin, etoposide, and cisplatin should be discussed with patients, as some were reported to have complete remission after these interventions. Although there are few literature studies and data to support ideal management, this case has shown that there may be utility for local radiation therapy in unresectable low-volume metastatic Leydig cell disease. A limitation in this report is that we will need long-term follow-up regarding this case. Given the rare occurrence of this malignancy, more data collection going forward will assist in the optimal management of future patients, given this diagnosis.

Evaluation of survival outcomes in patients with sporadic, advanced, unresectable well-differentiated pancreatic neuroendocrine tumors treated initially with octreotide LAR and subsequent therapeutical approaches on relapse. A real-world data set

Introduction. Somatostatin analogs (SSA) are widely used in the treatment of patients with well-differentiated neuroendocrine tumors (NET). There are limited reports about the role of octreotide LAR in first-line therapy of advanced pancreatic NET (pan-NET). This study aimed to evaluate the antiproliferative effect of octreotide LAR in patients with sporadic, advanced, unresectable pan-NET, based on progression-free survival (PFS). Material and methods. This was a retrospective analysis of 374 patients with pan-NET; 41 treated subjects were included. The primary endpoint was PFS defined as the time to disease progression (Response Evaluation Criteria in Solid Tumors: RECIST). Univariate and multivariate analyses were used to identify predictors of PFS. Secondary endpoints included overall survival (OS) and second-line therapies after progression. Results. There were 13 (32%) patients with G1 pan-NET and 28 (68%) with pan-NET G2, 21 female and 20 male, with mean age 55.4 (range 29–87). Median PFS was 9.0 months (95% CI 4.7–24.0). Subgroup analysis revealed that G1 and no-bulky liver disease ( &lt; 25% liver volume) were associated with significantly longer PFS. Univariate analysis confirmed a correlation between G1 [0.34 hazard rate (HR) of progression or death (95% CI 0.16–0.72)] and no-bulky liver disease HR = 0.31 (95% CI 0.13–0.71). Multivariable analysis demonstrated that only functional (secretory) pan-NET was associated as an independent factor with shorter PFS HR = 2.97 (95% CI 1.0–8.74). Median OS was 105.4 months (95% CI 40.0–172.0). After relapse following initial systemic therapy, the second line was used in 34 subjects, 3rd line in 18th, and 4th line in 9 subjects. Conclusions. Octreotide LAR shows moderate antiproliferative activity in pan-NET. Prolonged PFS may be associated with G1 and low-volume metastatic liver disease. In patients with progressive disease, various treatment options were used, which resulted in median OS of 105.4 months.

Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis.

IntroductionB cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients.MethodsFlow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs.ResultsB cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival.ConclusionThese data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN.

The Swedish national guidelines on prostate cancer, part 2: recurrent, metastatic and castration resistant disease

Objective There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods This is part 2 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. This part covers recurrence after local treatment and management of metastatic and castration resistant disease. Part 1 covers early detection, diagnostics, staging, patient support and management of non-metastatic disease. Results The 2022 Swedish guidelines include several new recommendations. Among these is a recommendation of a period of observation with repeated PSA tests for patients with approximately 10 years’ life expectancy who experience a BCR more than 2–5 years after radical prostatectomy, to allow for estimating the PSA doubling time before deciding whether to give salvage radiotherapy or not. Recent results from the PEACE-1 trial led to the recommendation of triple-treatment with a GnRH agonist, abiraterone plus prednisolone and 6 cycles of docetaxel for patients with high-volume metastatic disease who are fit for chemotherapy. The Swedish guidelines differ from the European ones by having more restrictive recommendations about genetic testing of and high-dose zoledronic acid or denosumab treatment for men with metastatic prostate cancer, and by recommending considering bicalutamide monotherapy for selected patients with low-volume metastatic disease. Conclusions The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines.

Achieving Consensus for Management of Hormone-Sensitive, Low-Volume Metastatic Prostate Cancer in Italy.

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

89Zirconium-labelled girentuximab (89Zr-TLX250) PET in patients with urothelial cancer (ZiPUP): A phase I trial of a novel staging modality for urothelial carcinoma.

TPS4609 Background: Bladder cancer is a lethal disease with a rising incidence. The current standard imaging modalities for staging are either CT of the chest, abdomen and pelvis or FDG PET/CT. However, there are issues with using these modalities for staging. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG is predominantly renally excreted and therefore has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Zirconium-89-Girentuximab (89Zr-TLX250) may have utility in the accurate staging of bladder and urothelial cancer, with less renal excretion as compared to FDG, however this has not previously been investigated. ZipUp is an investigator initiated trial. South Metropolitan Health Service WA is the trial sponsor. The study received funding and study drug support from Telix Pharmaceuticals Methods: ZiPUP is a single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. All participants will undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison. This trial aims to recruit 10 participants undergoing staging and 10 participants with known metastatic disease. The primary endpoint is effectiveness by assessing sensitivity and specificity in detecting lymph node metastases compared to FDG PET/CT; secondary endpoints are safety, tolerability, and feasibility. The first patient was enrolled in this single site study and the study is expected to be completed by December 2022. If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. Clinical trial information: NCT05046665.

Evaluation of the Indications for Sentinel Node Biopsy in Early-Stage Melanoma with the Advent of Adjuvant Systemic Therapy: An International, Multicenter Study

BackgroundPatients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5–10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma. The purpose was to assess the SN-positivity rate in early-stage melanoma and to identify primary tumor characteristics associated with high-risk nodal disease eligible for adjuvant systemic therapyMethodsAn international, multicenter retrospective cohort study from 7 large-volume cancer centers identified 3,610 patients with early primary cutaneous melanomas 0.8–2.0 mm in Breslow thickness (pT1b-pT2a; AJCC 8th edition). Patient demographics, primary tumor characteristics, and SNB status/details were analyzed.ResultsThe overall SNB-positivity rate was 11.4% (412/3610). Virtually all SNB-positive patients (409/412; 99.3%) were reclassified to AJCC stage IIIA. Multivariate analysis identified age, T-stage, mitotic rate, primary site and subtype, and lymphovascular invasion as independent predictors of sentinel node status. A mitotic rate of >1/mm2 was associated with a significantly increased SN-positivity rate and was the only significant independent predictor of high-risk SNB metastases (>1 mm maximum diameter).ConclusionsThe new treatment paradigm brings into question the role of SNB for patients with early-stage melanoma. The results of this large international cohort study suggest that a reevaluation of the indications for SNB for some patients with early-stage melanoma is required.

89Zirconium-labelled girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP): protocol for a phase I trial of a novel staging modality for urothelial carcinoma

IntroductionBladder cancer is a lethal disease with a rising incidence on a background of limited conventional imaging modalities for staging (either CT of the chest-abdomen-pelvis or 18F-fluorodeoxyglucose positron emitting tomography...