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Abstract 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

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundTo 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.MethodsThis 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.ResultsOf 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.ConclusionsPatients 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.

Background: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi. Methods: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data. Results: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m². In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L). Conclusion: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Palbociclib combined with an aromatase inhibitor (AI) has been shown to be effective in clinical trials for people with HR+/HER2− breast cancer that has spread to other areas of the body, such as the lungs or liver. Evidence of palbociclib effectiveness in routine clinical practice can provide complementary support for clinical trial findings. This study used electronic health records of people with breast cancer that had spread to their lungs and/or liver to determine how well palbociclib plus an AI worked compared to an AI alone. The study showed that palbociclib plus an AI compared with an AI alone was associated with a 38% or 27% reduction in the risk of death for patients with breast cancer that had spread to the lungs or liver, respectively. These findings support the use of palbociclib plus an AI for people whose breast cancer has spread to their lungs or liver. 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. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs) were found to be associated with a better clinical outcome in specific subtypes of breast cancer. Aim: To study the association between TILs and the prognosis of Egyptian patients with HER2-negative breast cancer metastatic to the viscera. Methods: This prospective study included 100 patients with HER2-negative metastatic breast cancer. Intratumoral TILs, stromal TILs, and CD4 and CD8 were examined in the pathological specimens and their relationship with survival and response to treatment was studied. Results: At a median follow-up period of 43 months, the median overall survival was 44.7 months (95%CI: 39.2-50.2) and the 5-year overall survival rate was 28%. A high level of CD8+ve TILs was associated with significantly longer overall survival (p < 0.001) and progression-free survival (p=0.043). There was no significant correlation between intratumoral TILs, stromal TILs, or CD4+ve and overall survival. Conclusions: A higher level of CD8+ve TILs is associated with better overall as well as progression-free survival in HER2-negative breast cancer with visceral metastases.

Abstract 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.

Background: Tumor-infiltrating lymphocytes (TILs) were found to be associated with a better clinical outcome in specific subtypes of breast cancer. Aim: To study the association between TILs and the prognosis of Egyptian patients with HER2-negative breast cancer metastatic to the viscera. Methods: This prospective study included 100 patients with HER2-negative metastatic breast cancer. Intratumoral TILs, stromal TILs, and CD4 and CD8 were examined in the pathological specimens and their relationship with survival and response to treatment was studied. Results: At a median follow-up period of 43 months, the median overall survival was 44.7 months (95%CI: 39.2-50.2) and the 5-year overall survival rate was 28%. A high level of CD8+ve TILs was associated with significantly longer overall survival (p<0.001) and progression-free survival (p=0.043). There was no significant correlation between intratumoral TILs, stromal TILs, or CD4+ve and overall survival. Conclusions: A higher level of CD8+ve TILs is associated with better overall as well as progression-free survival in HER2-negative breast cancer with visceral metastases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article reviews studies evaluating the efficacy and safety of eribulin chemotherapy in patients with HER2-negative advanced breast cancer. It analyzes the results derived from large randomized studies, highlights the main advantages peculiar to eribulin, and describes the key mechanisms of the antitumor activity displayed by the drug. Among those presented, there are significant retrospective studies evaluating the role of eribulin chemotherapy in late and early advanced breast cancer treatment lines, as well as an analysis of surveys aimed to evaluate the efficacy of the drug in various clinical settings (for visceral metastases, brain lesion, and in elderly patients). This article reflects the main results of Russian population analyses evaluating the efficacy and safety of eribulin chemotherapy in routine clinical practice.

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). 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. 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). 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. ClinicalTrials.gov, number NCT01715285 • AAP+ADT showed survival benefit in mCSPC men regardless of visceral disease status. • Men with liver metastases had a poorer prognosis than those with lung metastases. • A benefit in OS and rPFS was not seen in the small group of men with liver metastases. [ABSTRACT FROM AUTHOR]

Abstract 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 lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/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 lungw/o liver metastases than in those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P

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. [ABSTRACT FROM AUTHOR]

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.

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 lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/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 lungw/o liver metastases than in those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P < .001; liverw/o lung vs. lungw/o liver hazard ratio (HR) 1.70; lung and liver vs. lungw/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 lungw/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods: Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N=521) and postmenopausal women untreated for ABC (PALOMA-2; N=666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Results: Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases,median PFS (mPFS) was 9.2months with palbociclib plus fulvestrant versus 3.4months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3months with palbociclib plus letrozole versus 12.9months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Conclusions: Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Fulvestrant is a medication that is approved as first and second-line treatment in patients with hormone receptor positive advanced breast cancer. In clinical practice, fulvestrant is still used beyond the second line of treatment. This study investigated the use of fulvestrant in a Saskatchewan population of women with advanced breast cancer. We found that fulvestrant is effective when used in both the early and later lines of treatment, although the benefit is more pronounced in the earlier line of therapy. Women with disease affecting their visceral organs such as lung, liver or peritoneum had decreased disease control and survival on fulvestrant. Women who had received chemotherapy after fulvestrant and had a clinical response to fulvestrant had better survival. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: 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.)

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.

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.)