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The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting., (© 2024. The Author(s).)

Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and alterations of DNA repair genes). Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment., (© 2024. The Author(s).)

A cyclin-dependent kinase 4/6 inhibitor combined with endocrine therapy is the standard of care for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC), but real-world effectiveness data for patients with lung or liver metastases are limited. This retrospective study included data from the US Flatiron Health database of patients with HR+/HER2- mBC and lung or liver metastases treated with first-line palbociclib (PAL) plus an aromatase inhibitor (AI) or an AI alone in routine clinical practice. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed. A total of 891 patients were included (622 with lung metastasis, 376 with liver metastasis, and 107 with both lung and liver metastasis). After stabilized inverse probability of treatment weighting to balance patient characteristics, PAL + AI versus AI alone was associated with significantly prolonged OS (HR = 0.62; p < 0.001) and rwPFS (HR = 0.55; p < 0.001) in patients with lung metastases and numerically longer OS (HR = 0.73; p = 0.056) and significantly longer rwPFS (HR = 0.57, p < 0.001) for those with liver metastases. Overall, PAL + AI versus AI alone was associated with prolonged OS and rwPFS in routine clinical practice, supporting the use of first-line PAL + AI for patients with HR+/HER2- mBC with lung and/or liver metastases.

Clear cell renal cell carcinoma (ccRCC) usually spreads in the spinal region causing instability or spinal cord compression leading to neurological deficits. Therefore, surgical treatment is required for improving the outcome of patients. The aim of this study is to identify which prognostic factors could affect overall survival in patients affected by ccRCC. Methods: Retrospective cohort study of patients with ccRCC spinal metastases, surgically treated from November 2009 to April 2019. Demographic and clinical data were collected. The Kaplan−Meier method was used to estimate overall survival, and the log-rank test was used to evaluate differences in survival among potentially prognostic factors. Results: A total of 69 patients were surgically treated and followed up for a median period of 65 months. The average age at the time of surgery was 62.6 years old. The median overall survival (OS) was 34.7 months (95% CI 20.8−51.9) and 5-year OS was 31.2% (95% CI 19.2−44.1). A high Tokuhashi score (p = 0.0217), the presence of visceral metastases (p < 0.001), other bone metastases (p = 0.02012) and the kind of surgical treatment (p = 0.0395) are the main prognostic factors that influence the OS. Moreover, 3-year progression-free survival (PFS) was analyzed: the median PFS was 53.1 months and the % 3-year PFS was 62.9% (45.2−76.3). In the multivariate analysis, only pre-operative radiation therapy had a significant impact on 3-year PFS (95% CI 0.929−12.994, p = 0.0643). Conclusion: The results of this study suggest that the absence of visceral metastases and an aggressive surgery as en-bloc, when feasible, could prolong the survival rate and improve quality of life for patients.

Background: To evaluate the anatomic site(s) of initial disease progression in patients with castration resistant metastatic prostate cancer (mCRPC) in the presence or absence of pre-treatment visceral metastases while on systemic therapy., Methods: This is a retrospective cohort study of mCRPC patients who have baseline and at least one follow up bone scan and CT chest, abdomen and pelvis (CAP). Disease progression was determined by RECIST and/or ≥ 30% increase in automated bone scan lesion area score. Kaplan-Meier plot was used to estimate the median progression free survival and log-rank tests were used to compare anatomic sites., Results: Of 203 patients, 61 (30%) had pre-treatment visceral metastases. Patients with baseline visceral disease were 1.5 times more likely to develop disease progression (HR = 1.53; 95% CI, 1.03-2.26). Disease progression was a result of worsening bone scan disease (42% (16/38)) versus visceral (32% (12/38)) or lymph node disease (3% (1/38)) by CT or a combination thereof (23% (9/38)). Median time to progression (TTP) did not differ by anatomic location of initial progression (p = 0.86). Development of new lesions occurred in 50% of those visceral patients with soft tissue only progression and was associated with a significantly longer TTP (3.1 months (2.8-4.3 months) than those with worsening of pre-existing lesions (1.8 months (1.6-2.7 months); p = 0.04., Conclusions: Patients with pre-treatment visceral metastases in mCRPC are more likely to experience disease progression of bone disease with the initial anatomic site of progression similar to those without baseline visceral involvement., (© 2022. The Author(s).)

Background: A post-hoc analysis of the phase-3 LATITUDE study assessed the impact of abiraterone acetate plus prednisone (AA+P) on overall survival (OS) and radiographic progression-free survival (rPFS) in men with metastatic castration-sensitive prostate cancer (mCSPC) and visceral metastases (VM)., Methods: Newly diagnosed mCSPC patients were randomized (1:1) to AA+P and androgen deprivation therapy (ADT) or placebo+ADT. Patients with VM in liver or lungs with or without other soft tissue and bone metastases (based on CT/MRI) at baseline were analyzed, after 51.8 months' median follow-up. Co-primary endpoints, OS and rPFS, were analyzed., Results: Among 1199 patients enrolled, 228 (19%) had VM at baseline (114 each in AA+P and placebo groups), of which 53 (23.2%; AA+P = 29, Placebo = 24) had liver metastases and 117 (51.3%; AA+P = 60, Placebo = 57) had lung metastases. In patients with VM, treatment with AA+P versus placebo showed an improvement in OS (median 55.4 vs 33.0 months; HR = 0.582; 95%CI = 0.406-0.835;P = 0.0029) and rPFS (median 30.7 vs 18.3 months; HR = 0.527; 95%CI = 0.366-0.759;P = 0.0005), comparable to that of patients without VM. AA+P versus placebo in lung metastases patients was associated with greater improvement in OS (HR = 0.60; 95%CI = 0.35-1.04;P = 0.0678) than in liver metastases patients (HR = 0.82; 95%CI = 0.41-1.66;P = 0.5814). AA+P versus placebo showed improvement in rPFS in lung metastases patients (HR = 0.50; 95%CI = 0.29-0.89;P = 0.0157), but not in liver metastases patients (HR = 1.05; 95%CI = 0.53-2.09; P = 0.8970)., Conclusion: AA+P treatment improved both rPFS and OS in men with mCSPC and visceral disease, especially those with lung metastases. Men with liver metastases had a poorer prognosis and their optimal treatment remains to be defined., Registration: ClinicalTrials.gov, number NCT01715285., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SM, GL, UR, and PH are employees of Janssen Research & Development and hold company stock. KF has received personal fees from Amgen, Astellas, AstraZeneca, Bayer, Clovis, Curevac, Essa, Genentech, Janssen, Merck Sharp and Dohme (MSD), Orion, and Sanofi. KNC's institution has received funding from Janssen for this study. MÖ received personal fees from Janssen and Sanofi. SF has served on advisory boards for Janssen, Boehringer Ingelheim Pharma, and Aventis, and has received honorarium from Janssen, and travel and accommodation expenses from Aventis. GB and NM declared no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy., Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003-2019. A multivariate Cox proportional survival analysis was performed., Results: One hundred and eighty-six women with a median age of 63.5 years were identified-178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50-0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23-0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30-0.65), and absence of visceral metastasis, HR: 0.70 (0.50-0.97), were correlated with better OS., Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.

Usually late in the course of advanced prostate carcinoma, atypical nodal and distant metastases may be encountered. Accurate characterisation of disease spread and assessment of disease response have significant treatment and prognostic implications. Surveillance imaging, therefore, along with clinical and biochemical parameters, is a key factor in directing appropriate management. Atypical metastases may also require histological re-evaluation, as they may indicate differentiation into aggressive histologic subtypes, which can lead to management alteration. We present a pictorial review of the less common patterns of metastatic prostate carcinoma, to aid in timely recognition and diagnosis., Competing Interests: None., (© the authors; licensee ecancermedicalscience.)

Purpose: The purpose of this study was to estimate the overall survival (OS) in real-world clinical practice in patients with metastatic breast cancer (MBC) and visceral metastases (liver or lung) treated in the third-line setting with eribulin, gemcitabine or capecitabine overall and in the major clinical categories of MBC (TNBC, HR+/HER2-, and HER2+)., Methods: A retrospective, observational study was conducted with de-identified patient electronic health records from the Cancer Treatment Centers of America (CTCA). Patients with a diagnosis of metastatic breast with lung or liver metastases, and treated with eribulin, gemcitabine, or capecitabine as third-line therapy were included in the analysis. Landmark survival was calculated as percentage of patients alive at 6, 12, 24, and 36 months. Overall survival was compared between treatment arms within TNBC and HR+/HER2- using log-rank analysis. Cox regression analyses was performed to estimate hazard ratios for comparison of treatments within TNBC and HR+/HER2- subtype., Results: 443 patients with liver or lung metastases received third-line therapy with eribulin (n = 229), gemcitabine (n = 134), or capecitabine (n = 80). Eribulin patients had a higher percentage of patients alive at all landmark timepoints vs. gemcitabine, and a higher percentage of patients alive until 36 months vs. capecitabine. Median survival times showed that overall, and within the TNBC and HR+/HER2- subtype, patients receiving eribulin had a numerically higher median overall survival., Conclusions: This real-world evidence study is consistent with randomized clinical trial data and demonstrates consistency of eribulin effectiveness in MBC patients with lung or liver metastases overall and in TNBC and HR+/HER2- disease.

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01-1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06-1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.

Background: Distant metastasis, particularly visceral metastasis (VM), represents an important negative prognostic factor for prostate cancer (PCa) patients. However, due to the lower rate of occurrence of VM, studies on these patients are relatively rare. Consequently, studies focusing on prognostic factors associated with PCa patients with VM are highly desirable., Aim: To investigate the prognostic factors for overall survival (OS) in PCa patients with lung, brain, and liver metastases, respectively, and evaluate the impact of site-specific and number-specific VM on OS., Methods: Data on PCa patients with VM were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Univariate and multivariate Cox regression analyses were used to analyze the association between clinicopathological characteristics and survival of patients with different site-specific VM. Kaplan-Meier analyses and Log-rank tests were performed to analyze the differences among the groups., Results: A total of 1358 PCa patients with site-specific VM were identified from 2010 to 2015. Older age (> 70 years) ( P < 0.001), higher stage (T3/T4) ( P = 0.004), and higher Gleason score (> 8) ( P < 0.001) were found to be significant independent prognostic factors associated with poor OS in PCa patients with lung metastases. Higher stage (T3/T4) ( P = 0.047) was noted to be the only independent risk factor affecting OS in PCa patients with brain metastases. Older age (> 70 years) ( P = 0.010) and higher Gleason score (> 8) ( P = 0.001) were associated with shorter OS in PCa patients with liver metastases. PCa patients with isolated lung metastases exhibited significantly better survival outcomes compared with PCa patients with other single sites of VM ( P < 0.001). PCa patients with a single site of VM exhibited a superior OS compared with PCa patients with multiple sites of VM ( P < 0.001)., Conclusion: This is the first Surveillance, Epidemiology, and End Results-based study to determine prognostic factors affecting OS in PCa patients with different site-specific VM. Clinical assessments of these crucial prognostic factors become necessary before establishing a treatment strategy for these patients with metastatic PCa., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Endocrine therapy is the preferred treatment for patients with hormone receptor -positive metastatic breast cancer (MBC). While visceral metastasis is a negative prognostic factor, few studies have distinguished between the prognoses of patients with metastases at different visceral sites., Patients and Methods: In total, 398 patients receiving fulvestrant 500 mg at a single center over a 6-year period were analyzed. Logistic regression models were used to identify the prognostic factors associated with progression-free survival (PFS). Kaplan-Meier analysis was used to compare the PFS of patients with lung and liver metastases., Results: Baseline visceral metastases were present in 233 patients, including 138 with lung w/o liver metastases (lung metastases without liver involvement), 51 with liver w/o lung metastases (liver metastases without lung involvement) and 41 with lung and liver metastases. The median PFS was 6.8 months (5.6 and 9.2 months for visceral and nonvisceral metastases, respectively, P = .028). PFS was longer in patients with lung w/o liver metastases than in those with liver w/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P < .001; liver w/o lung vs. lung w/o liver hazard ratio (HR) 1.70; lung and liver vs. lung w/o liver HR 2.85). Patients with liver metastases experienced significantly worse PFS than those without liver involvement (3.7 vs. 9.2 months, P < .001). PFS benefits were observed in patients with longer disease-free intervals, no liver metastases, and no previous chemotherapy., Conclusion: Fulvestrant treatment benefited patients with lung w/o liver or nonvisceral metastases. When treating hormone receptor-positive/HER2-negative MBC patients with endocrine therapy, it is important to differentiate patients with lung metastases from those with liver metastases., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: In this paper, we present a prospective observational study, which determines the incidence of bone metastases and its correlation with hormonal receptors (estrogen receptor [ER]/progesterone receptor [PR]) and human epidermal growth factor receptor 2 (HER2) in breast cancer., Materials and Methods: From October of 2015 to July 2017, 262 patients were eligible for the study, of which 98 patients presented/developed bone metastases. ER/PR and HER2 receptor status were determined, and bone scintigraphy with a technetium-99 m was carried out on each patient during the study., Results: The incidence rate of bone metastases as found in this study was 25.25%, and the mean and median age at diagnosis were 47.23 and 46, respectively (age range = 28-80). Bone metastases were more prevalent in ER-positive tumors (P = 0.043), tumors with lymph node positivity (P = 0.002), and lower grade tumors (P = 0.002), whereas visceral metastases were more common with ER-tumors (P = 0.005), tumors with higher grade (P = 0.012), and tumors with lymph node positivity (P = 0.034). In this study cohort, the spine and pelvis were the most commonly involved subsites of bone metastases (P < 0.001)., Conclusion: This study demonstrates that the metastatic patterns in breast cancer strongly correlate with various breast cancer subtypes, mainly designated by ER, PR, and HER2. Hormone receptor-positive tumors show a predilection for bones as the first site of relapse compared to hormone-receptor-negative tumors which have a proclivity to develop as visceral metastases., Competing Interests: None

Background: Risk factors of visceral metastases in prostate cancer (PCa) patients are unclear. The aim of this study is to investigate the risk factors of developing visceral metastases at diagnosis and the impact of these risk factors on the survival of patients with visceral metastatic PCa., Methods: Patients with visceral metastases at the time of diagnosis of [2010-2015] PCa were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Visceral metastatic distribution data were provided for liver, lung, and brain. The overall survival (OS) was calculated by the Kaplan-Meier method. Multivariable logistic and Cox regression models were performed to identify risk factors and analyze survival outcomes., Results: A total of 13,092 eligible patients with stage IV PCa were identified from SEER database. A total of 598 patients developed visceral metastases at diagnosis among these patients. In multivariable analyses, patients with PSA >80 ng/mL had 1.545-fold higher risk of developing visceral metastases compared with those with PSA <20 ng/mL (P<0.001). The presence of bone metastasis and lymph node (LN) metastases were represented as risk factors of visceral metastases in stage IV PCa patients. Patients with two or three metastatic sites had 1.604-fold higher risk of shorter OS compared with those with one metastatic site (P<0.05). And patients with bone plus visceral metastases had 1.410-fold higher risk of shorter OS compared with those with visceral metastasis only (P<0.05). Age ≥70 had 1.621-fold higher risk of shorter OS compared with those with age <70 (P<0.05). T4 stage had 1.476-fold higher risk of shorter OS compared with those with T1 stage (P<0.05)., Conclusions: The incidence rate was increased among patients with visceral metastases in stage IV PCa at diagnosis. PSA over 80 ng/mL, the presence of bone metastasis and the presence of LN metastases were risk factors associated with a higher rate of development of visceral metastases in stage IV PCa patients. The presence of visceral plus bone metastases, two or three sites, age over 70, and T4 stage represent prognostic factors on survival outcomes in visceral metastatic PCa patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.05.31). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients' dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12⁻10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07⁻0.67; p = 0.008), SLNB (Sentinel Lymph Node Biopsy) status (OR, 3.05; 95% CI, 1.06⁻8.78; p = 0.039) and TERT -mutated trunk lesions (OR, 3.78; 95% CI, 1.35⁻10.6; p =  0.011) were significantly associated with the risk of developing a visceral spreading as first site of progression using multivariate logistic regression analysis. These results were confirmed in the external validation control group. Therefore, in trunk primary melanomas, due to their high risk of progression to visceral sites, we encourage somatic TERT mutation analysis at diagnosis to identify those patients who would potentially benefit from a more intensive follow-up protocol and a prompt initiation of therapy.

Aim: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases., Materials and Methods: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma)., Results: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193)., Conclusion: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Professor Donald Coffey and his laboratory pioneered studies showing the relationships between nuclear shape and cellular function. In doing so, he and his students established the field of nuclear morphometry in prostate cancer. By using perioperative tissues via biopsies and surgical sampling, Dr. Coffey's team discovered that nuclear shape and other pathologic features correlated with clinical outcome measures. Cancer cells also exist outside of solid tumor masses as they can be shed from both primary and metastatic lesions into the circulatory system. The pool of these circulating tumor cells (CTCs) is heterogeneous. While some of these CTCs are passively shed into the circulation, others are active metastasizers with invasive potential. Advances in nanotechnology now make it possible to study morphologic features such as nuclear shape of CTCs in the bloodstream via liquid biopsy. Compared to traditional tissue sampling, liquid biopsy allows for minimally invasive, repetitive, and systemic disease sampling, which overcomes disease misrepresentation issues due to tumor temporospatial heterogeneity. Our team developed a novel liquid biopsy approach, the NanoVelcro assay, which allows us to identify morphologic heterogeneity in the CTC compartment. By applying classical methods of nuclear morphometry, we identified very small nuclear CTCs (vsnCTCs) in prostate cancer patients. Our initial studies showed that vsnCTCs strongly correlated with unfavorable clinical behaviors including the disposition to visceral metastases. These approaches may continue to yield additional insights into dynamic clinical behaviors, which creates an opportunity for more comprehensive and accurate cancer profiling. Ultimately, these advancements will allow physicians to employ more accurate and personalized treatments, helping the field reach the goal of true precision medicine.

Purpose: We developed and validated algorithms to identify metastases and breast cancer recurrence in Danish medical registries. We computed the incidence rate (IR) and hazard ratios (HRs) to evaluate predictors of these outcomes in stage II/III breast cancer patients., Methods: We included all women in Denmark diagnosed during 1999-2011 with regional or stage II/III breast cancer. Demographic, tumor, and treatment data were ascertained from population-based health registries. To facilitate diagnostic work-up of the primary cancer, follow-up began 180 days after diagnosis and continued until recurrence/metastases, death, or 31 December 2012, whichever occurred first. We computed the positive predictive values (PPVs) of recurrence, bone metastases, and visceral metastases using medical records as a gold standard. We calculated the cumulative incidence, IR per 10,000 person years, and used Cox regression to compute the HRs and associated 95% confidence intervals (95% CI) for each outcome., Results: Among 23,478 patients, 7073 had regional stage and 16,405 had stage II/III breast cancer. The PPV for recurrence was 72.6% (95% CI 59.3, 83.3%). The PPVs for bone and visceral metastases were 92.3% (95% CI 69.3-99.2%) and 70.8% (95% CI 51.1, 85.9%), but had low sensitivity. Five-year cumulative incidence of recurrence, bone metastases, and visceral metastases were 18.4, 2.2, and 5.2%, with corresponding 5-year IRs of 540 (95% CI 524, 557), 60 (95% CI 55, 65), and 144 (95% CI 136, 152), respectively. Predictors of recurrence and metastases included age, stage, hormone receptor status, and cancer treatment., Conclusion: Our algorithms show moderate to high PPVs for recurrence and metastases. The IRs of metastases were lower compared with other registry-based cohort studies, so may be underestimated in Danish registries.

Background: Although visceral metastases (VMs) are widely recognized to portend worse prognoses compared with bone and lymph metastases in men with metastatic castration-resistant prostate cancer (mCRPC), little is known about what predicts VMs and the extent to which men with VMs do worse., Objective: To determine whether men with VMs at initial mCRPC diagnosis have worse overall survival (OS) and identify predictors of VMs., Design, Setting, and Participants: We analyzed 494 men diagnosed with castration-resistant prostate cancer post-1999 and no known metastases from five Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital (SEARCH) database who later developed metastases. Radiology scans within 30 d of initial metastasis diagnosis were reviewed to collect information on bone, visceral, and lymph node metastases. We analyzed the 236 men who had a computed tomography scan performed., Outcome Measurements and Statistical Analysis: Predictors of VMs and OS were evaluated using logistic regression and Cox models, respectively., Results and Limitations: Of the 236 mCRPC patients, 38 (16%) had VMs. Regarding VMs, 19 patients (50%), 8 patients (21%), and 16 patients (42%) had metastases in the liver, lungs, and other locations, respectively. VMs were a predictor of OS on crude analysis (hazard ratio [HR]: 1.88; 95% confidence interval [CI], 1.30-2.72; p=0.001) and after risk adjustment (HR: 1.84; 95% CI, 1.24-2.72; p=0.002). Age, year, treatment center, prostate-specific antigen (PSA), and time from CRPC to metastases were significant in predicting OS (all p<0.05). None of the variables tested were associated with having VMs (all p > 0.09). Prospective studies and larger cohorts are needed to validate our findings., Conclusions: Demographic, tumor, and PSA kinetic characteristics were not predictive of having VMs, but VMs predicted worse OS., Patient Summary: Because patients with VMs have worse overall survival, further research is needed to develop better biomarkers and thus diagnose those with VMs at earlier stages in their disease course., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The prognosis of patients diagnosed with metastatic prostate cancer seems to be modulated by factors such as the number and site of metastases. Our objective is to evaluate survival outcomes according to the number and site of metastases in our series of metastatic patients over the last 15 years., Materials and Methods: A retrospective analysis was performed on patients diagnosed between 1998 and 2014. We analyzed overall survival and progression-free survival, depending on the number and location of metastases on patients with newly diagnosed metastatic prostate cancer. Other potential prognostic factors were also evaluated: age, clinical stage, PSA at diagnosis, Gleason, PSA nadir, time till PSA nadir and first-line or second-line treatment after progression., Results: We analyzed a series of 162 patients. The mean age was 72.7yr (SD: 8.5). The estimated median overall survival was 3.9 yr (95% CI 2.6-5.2). The overall survival in patients with only lymph node metastases was 7 yr (95% CI 4.1-9.7), 3.9 (95%CI 2.3-5.5) in patients with only bone metastases, 2.5 yr (95% CI 2-2.3) in lymph nodes and bone metastases, and 2.2 yr (95% CI 1.4-3) in patients with visceral metastases (P<.001). In multivariate analysis, the location of metastasesis significantly associated with overall survival and progression-free survival. The number of metastases showed no association with survival., Conclusions: The site of metastases has a clear impact on both overall survival and progression-free survival. Patients with only lymph node involvement had a better prognosis. The number of metastases showed no significant impact on survival in our series., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease.

Background: The objective of this study was to analyze the impact of visceral metastases in castration-resistant prostate cancer (CRPC) treated with abiraterone., Materials & Methods: All CRPC patients received abiraterone 1000 mg daily plus prednisone 10 mg orally daily. Liver and lung metastases were considered as visceral metastases., Results: Of 265 CRPC patients, 49 had visceral metastases. Results on progression-free survival were not significantly different in patients with or without visceral metastases. Conversely, the median overall survival between the two groups was 12.4 and 18.5 months (p = 0.01), respectively, and median overall survival of patients with liver-only disease versus other sites was 10.5 versus 18.5 months (p = 0.006), respectively., Conclusion: Visceral disease appears to be an important predictor of clinical outcome in CRPC patients treated with abiraterone.

Background: Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraLEveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO)+EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR(+), HER2(-) ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%)., Methods: Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE+EXE versus PBO+EXE in a prospectively defined subgroup of patients with visceral metastases., Findings: At a median follow-up of 18 months, EVE+EXE significantly prolonged median PFS compared with PBO+EXE both in patients with visceral metastases (N=406; 6.8 versus 2.8 months) and in those without visceral metastases (N=318; 9.9 versus 4.2 months). Improvements in PFS with EVE+EXE versus PBO+EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE+EXE versus 2.8 months with PBO+EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE+EXE treatment more than tripled median PFS compared with PBO+EXE (6.8 versus 1.5 months)., Interpretation: Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR(+) HER2(-) ABC regardless of the presence of visceral metastases., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Docetaxel is the current first-line treatment for castration-resistant prostate cancer (CRPC), following failure to respond to maximal androgen blockade (MAB). Patients who fail to respond to docetaxel may receive cabazitaxel or abiraterone; however, there are no recommendations on which of these two agents should be used first. Here, we present a case of a male patient suffering from CRPC with liver and lymph node metastases, in which abiraterone achieved a partial response, according to RECIST criteria. In the literature, visceral involvement in patients with advanced prostate cancer is an infrequent occurrence; it affects 18-22% of patients. In the pivotal study concerning docetaxel-resistant patients, abiraterone was compared with a placebo and the forest plot for survival demonstrated that patients with visceral involvement have significantly benefited from abiraterone. In the TROPIC trial comparing cabazitaxel with mitoxantrone, the proportion of patients with visceral disease was ∼25% in both arms and there was no difference in overall survival in this subgroup of patients. In our case, we observed a significant activity of abiraterone in lymph node and liver metastases. If confirmed in large studies, this observation may raise concerns over whether to treat patients suffering from CRPC and visceral metasis with chemotherapy or hormone therapy.