Metastatic Cancer Patients Research Articles

Prognostic role of prostate specific antigen kinetics in primary high volume metastatic hormonal sensitive prostate cancer treated with novel hormonal therapy agents

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.

A comprehensive investigation of associations between cell death pathways and molecular and clinical features in pan-cancer.

Regulated cell death (RCD) pathways play significant roles in tumorigenesis. However, systematic investigation into correlations between RCD and various molecular and clinical features, particularly anti-tumor immunity and immunotherapy response in pan-cancer remains lacking. Using the single-sample gene set enrichment analysis, we quantified the activities of six RCD pathways (apoptosis, autophagy, ferroptosis, cuproptosis, necroptosis, and pyroptosis) in each cancer specimen. Then, we explored associations of these six RCD pathways with tumor immunity, genomic instability, tumor phenotypes and clinical features, and responses to immunotherapy and targeted therapies in pan-cancer by statistical analyses. Our results showed that the RCD (except autophagy) activities were oncogenic signatures, as evidenced by their hyperactivation in late stage or metastatic cancer patients, positive correlations with tumor proliferation, stemness, genomic instability and intratumor heterogeneity, and correlation with worse survival outcomes in cancer. In contrast, autophagy was a tumor suppressive signature as its associations with molecular and clinical features in cancer shows an opposite pattern compared to the other RCD pathways. Furthermore, heightened RCD (except cuproptosis) activities were correlated with increased sensitivity to immune checkpoint inhibitors. Additionally, elevated activities of pyroptosis, autophagy, cuproptosis and necroptosis were associated with increased drug sensitivity in a broad spectrum of anti-tumor targeted therapies, while the elevated activity of ferroptosis was correlated with decreased sensitivity to numerous targeted therapies. RCD (except autophagy) activities correlate with unfavorable cancer prognosis, while the autophagy activity correlate with favorable clinical outcomes. RCD (except cuproptosis) activities are positive biomarkers for anti-tumor immunity and immunotherapy response.

Patient preferences for metastatic prostate cancer treatment: a discrete choice experiment

BackgroundTo examine the preference weightings for risk/benefit attributes of therapy in metastatic prostate cancer(mPC) patients, encompassing hormone-sensitive(mHSPC) and castration-resistant(mCRPC) settings. Patients and MethodsA non-interventional cross-sectional survey employing a discrete choice experiment was conducted, recruiting 200 mHSPC and 100 mCRPC patients within 5 years of diagnosis from the urology and oncology specialty clinics between Feb 2023 and Jul 2023. Patients were randomized into 2 blocks of 9 questions, choosing 1 out of 2 medication profiles consisting five attributes, each with 3 levels, determined from a group interview of 5 patients. A mixed logit model estimated attribute-level preference weightings, with tradeoff points calculated. ResultsMedian age was 75(IQR:71-81), 170(56.7%) had no income, 245(81.7%) cared for themselves, mean maximum out-of-pocket treatment cost was US$20,456(SD:43,568), and 160(53.3%) claimed not to consider further treatment when cost exceeding their affordability. Patients favoured self-care ability(4.37,P<.001) and life expectancy extension(2.83,P<.001), disfavoured adverse effects (-6.97,P<.001) and treatment cost(in HK$million or USD$128,205)(-3.14,P<.001). mCPRC patients was more sensitive to treatment cost(-3.61vs-2.97), life expectancy extension(3.47vs2.55) and adverse effects(-7.55vs-6.80) compared to mHSPC patients. Higher financial affordability patients exhibited higher sensitivity to self-care ability(4.89vs4.02) and adverse effects(-7.57vs-6.70). ConclusionThe chance of adverse effects was pivotal in treatment decisions, followed by self-care ability, with cost remaining a major access barrier. Micro AbstractExamining the preference weightings for risk/benefit attributes of therapy in metastatic prostate cancer patients, we recruited 200 hormone-sensitive and 100 castration-resistant patients for a cross-sectional discrete choice experiment survey. A mixed logit model estimated attribute-level preference weightings, calculating tradeoff points. The chance of adverse effects and self-care ability were pivotal in treatment decisions, with cost remaining a major access barrier.

Skin Rash in metastatic Hormone Sensitive Prostate Cancer Patients Treated with Apalutamide: A Retrospective Multicenter Study in Korea

PurposeSkin rash is a common adverse event in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with apalutamide. This study aims to investigate the incidence rate of skin rash and the predictive value of inflammation markers for skin rash in real-world Korean patients. Materials and MethodsWe conducted a retrospective analysis of patients with prostate cancer (PCa) who received apalutamide across 18 institutions in Korea, with a follow-up period of at least three months. A total of 218 patients were evaluated. ResultsAmong the 214 patients analyzed, 78 (36.4%) developed a skin rash. The severity of the rash was classified as grade 1 (G1) in 27 patients (12.6%), grade 2 (G2) in 29 patients (13.5%), and grade 3 (G3) in 22 patients (10.3%). The median time to onset of any skin rash was 65.5 days (interquartile range, IQR 31.0-88.0). There were no significant differences in inflammation markers before apalutamide administration between patients who developed a rash and those who did not. However, the Monocyte-to-Lymphocyte Ratio (MLR) and Systemic Immune-Inflammation Response Index (SIRI) were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.006, p=0.013, respectively) before apalutamide treatment. After 3 months, Platelet-to-Lymphocyte Ratio (PLR) and SIRI were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.010, p=0.025, respectively) ConclusionIn a real-world cohort of Korean patients, skin rash occurred in 36.4% of cases, with a median time to onset of 65.5 days. Grade 3 skin rash developed in 10.3% of cases. While MLR and SIRI were significantly higher in the G2 plus G3 group, these markers cannot be considered reliable predictors due to a low area under the curve (AUC < 0.7) before apalutamide treatment. However, increased levels of PLR, SII, and SIRI could potentially be useful for monitoring for the risk of severe rash development in these patients.

ASO Author Reflections: It Does Not Matter Whether Radical Prostatectomy is Performed in High-Risk Localized Disease or at the Oligometastatic Stage.

Radical prostatectomy (RP) alone has traditionally been considered insufficient for patients with high-risk localized prostate cancer (HRPC) owing to the frequent need for adjuvant salvage radiotherapy or androgen deprivation therapy (ADT) following surgery. Previously, systemic therapy, such as ADT, was the standard treatment for metastatic prostate cancer (PC) patients; RP was not considered viable for these patients. However, since 2015, there has been a recognition that metastatic PC patients can be categorized based on the extent of their metastases, leading to the consideration of RP for some metastatic cases. In recent years, the concept of cytoreductive RP has gained traction; studies suggest that it may improve survival rates in metastatic PC patients through mechanisms, such as tumor debulking and enhancement of the immune response. A meta-analysis of retrospective studies has shown that cytoreductive RP is associated with higher cancer-specific survival rates at 1-year, 3-year, and 5-year intervals compared with systemic therapy alone. In our study, which followed HRPC and oligometastatic PC patients for an average of 46 months, we observed biochemical recurrence in 17.8% of HRPC and 13% of oligometastatic patients, with overall survival rates of 96.4% and 87%, respectively. Although prospective or randomized studies are still lacking, current retrospective studies, including our own, suggest promising outcomes for RP in HRPC and oligometastatic patients. With the increasing prevalence of robotic surgery, improved pelvic anatomy observation, and growing surgical confidence, the realization of prospective randomized study results may not be far off.

Effects of Concurrent Administration of Spironolactone in Veterans with Metastatic Prostate Cancer Receiving Abiraterone: A Real-World Retrospective Study.

Prostate cancer is the most common cancer in men in the United States with low survival rates once metastasized. Abiraterone is approved for use in castrate-sensitive and castrate-resistant prostate cancer and is used extensively in the Veterans Affairs (VA) healthcare system. Spironolactone, a diuretic used to treat heart failure, edema, ascites, and hypertension, may increase androgen levels and reduce effectiveness of abiraterone when used concurrently to treat prostate cancer patients. While previous case studies support this, no large epidemiology studies have been conducted. The current study utilizes the large, VA prostate cancer data core and evaluates the effect of concomitant spironolactone on efficacy of abiraterone treatment in metastatic prostate cancer patients. The study selected 18,943 veterans with metastatic prostate cancer on abiraterone treatment. Of these, 581 patients (3.1%) were also on concomitant spironolactone. The concomitant treatment group, abiraterone + spironolactone, significantly differed from the abiraterone-only group in body mass index, prevalence rates of heart failure and liver disease, and being previously treated with docetaxel. A 1:1 propensity score matching method was used to balance sample sizes and baseline traits between the two treatment groups, abiraterone versus abiraterone + spironolactone. Kaplan-Meier curves and Cox proportional hazard model were used to compare 5-year overall survival and all-cause mortality outcomes, respectively, between the two groups. After propensity score matched, the abiraterone + spironolactone group was treated with abiraterone significantly longer than the abiraterone-only group (mean ± standard deviation days 549.0 ± 552.3 vs. 435.5 ± 474.1; p = 0.0002) and had a higher 5-year overall survival rate (44% vs. 37%; p = 0.0116). Veterans with metastatic prostate cancer treated with abiraterone + spironolactone also had a lower 5-year all-cause mortality compared to those only on abiraterone (hazard ratio 0.80, 95% confidence intervals 0.61-0.96; p = 0.012). This large VA observational study suggests that concomitant use of spironolactone does not compromise cancer control or survival of metastatic prostate cancer patients treated with abiraterone.

Assessing the predictive value of intraductal carcinoma of the prostate (IDC-P) in determining abiraterone efficacy for metastatic hormone-sensitive prostate cancer (mHSPC) patients.

This study explored the value of intraductal carcinoma of the prostate (IDC-P) in predicting the efficacy of abiraterone treatment in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A retrospective study of 925 patients who underwent prostate biopsies to detect IDC-P was conducted, with participants divided into two cohorts. The first cohort of 165 mHSPC patients receiving abiraterone treatment was analyzed to compare therapeutic effectiveness between IDC-P positive and negative cases. Utilizing propensity score matching (PSM) to reduce bias, outcomes such as PSA response, progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival were assessed. Additionally, the second cohort of 760 mHSPC patients compared the efficacy of abiraterone with conventional hormone therapy, focusing on differences between IDC-P positive and negative individuals. After PSM, our first cohort included 108 patients with similar baseline characteristics. Among them, 50% (54/108) were diagnosed with IDC-P, with 22.2% (12/54) having IDC-P pattern 1 and 77.8% (42/54) with IDC-P pattern 2. While no notable difference was seen in PSA responses between IDC-P positive and negative patients, IDC-P presence linked to worse clinical outcomes (PSA-PFS: 18.6 months vs. not reached [NR], p = 0.009; rPFS: 23.6 months vs. NR, p = 0.020). Further analysis showed comparable outcomes for IDC-P pattern 1 but significantly worse prognosis for IDC-P pattern 2 (PSA-PFS: 18.6 months vs. NR, p = 0.002; rPFS: 22.4 months vs. NR, p = 0.010). Subgroup analysis revealed IDC-P pattern 2 consistently predicted poorer outcomes across patient subgroups. Remarkably, both IDC-P positive and negative patients gained more from androgen deprivation therapy with abiraterone than conventional treatment, with IDC-P negative patients showing a more significant survival advantage, supported by better hazard ratios (0.47 and 0.66). This study found that IDC-P, especially pattern 2, predicts poor prognosis in mHSPC patients on abiraterone therapy. Also, abiraterone's advantage over hormone therapy is reduced in cases with IDC-P compared to those without.

Assessment of the therapeutic efficacy of [177Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.

Radioligand therapy (RLT) with 177Lu-labelled prostate specific membrane antigen ([177Lu]Lu-PSMA-X, referring with "PSMA-X" to a generic PSMA chemical compound) inhibitors has emerged as a viable treatment option in metastatic castration resistant prostate cancer patients having previously progressed on taxane and androgen receptor inhibitors. The aim of this study was to perform a systematic review and meta-analysis to assess the therapeutic efficacy of [177Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer. Searches in several bibliographic databases were made using relevant key words, and articles published up to March 2024 were included. The endpoints included prostate specific antigen (PSA) response rate (RR), progression-free survival, and overall survival. Individual patient data were pooled when feasible. PSA50 was defined as the median proportion of patients achieving at least a 50% decline in serum PSA from baseline. A meta-analysis of the PSA50 response rate (proportion meta-analysis) was performed, generating pooled estimates and 95% confidence intervals (95% CI). From the initially selected 8,414 studies published between 2019 and 2023, 24 were included in the [177Lu]Lu-PSMA-X treated group and 17 in the taxane treated group. Our findings show that [177Lu]Lu-PSMA-X RLT yielded comparable PSA50 responses in taxane-naïve patients versus those receiving taxane chemotherapy, despite considerable study heterogeneity. Notably, the taxane-naïve group had more extensive pretreatment. This meta-analysis combines the largest cohorts of taxane-naïve mCRPC patients treated with [177Lu]Lu-PSMA-X RLT and taxane-treated mCRPC. It underscores similar PSA50 response rates in both groups, suggesting a potential role for [177Lu]Lu-PSMA-X RLT in taxane-naïve patients who cannot or choose not to undergo chemotherapy.

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era

BackgroundTreatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider.MethodsNewly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017–December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan–Meier analysis. Outcomes were assessed at a minimum of 6 months’ follow-up (cutoff: 30 June 2021).ResultsAmong 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0–1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7–29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5–7.6), 5.2 (95% CI: 4.6–7.6), and 2.3 (95% CI: 2.1–3.0) months, respectively; for the subgroup of patients with ECOG PS 0–1, rwToT was 9.4 (95% CI: 5.0–20.8), 7.1 (95% CI: 5.0–10.1), and 2.9 (95% CI: 2.2–4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9–17.9), 14.8 (95% CI: 10.5–19.4), and 9.1 (95% CI: 7.1–11.5) months; for the subgroup of patients with ECOG PS 0–1, median rwOS was 25.1 [95% CI: 14.9–not reached (NR)], 17.6 (95% CI: 14.3–NR), and 11.3 (95% CI: 9.2–21.3) months, respectively. For ECOG PS 0–1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9–NR) and NR for PDM and PDC, respectively. For ECOG PS 0–1 and PD-L1 &amp;lt;50% patients, median rwOS was 14.3 (95% CI: 10.1–NR) and 11.2 (95% CI: 9.1–21.3) months for PDC and PBC, respectively.ConclusionOur real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

Cancer Therapy-Induced Encephalitis

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients’ quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments.

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.

Ultralow Prostate-Specific Antigen (PSA) Levels and Improved Oncological Outcomes in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Patients Treated with Apalutamide: A Real-World Multicentre Study.

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: <0.02 ng/mL (ultralow), 0.02-0.2 ng/mL, and >0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02-0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.

Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey.

Novel therapies for metastatic castration-resistant prostate cancer (mCRPC) have improved patient outcomes. However, there is uncertainty on the optimal selection of therapeutic agents for subsequent lines of therapy. We conducted a comprehensive review of published evidence from pivotal clinical trials and recent guidelines for the treatment of mCRPC. We further identify gaps in knowledge and areas for future research. Key considerations to help guide treatment selection for patients with mCRPC include personal treatment history, individual clinical characteristics, symptoms, prognosis, availability of clinical trials, and other patient-specific factors. Genetic testing and prostate-specific membrane antigen-targeted imaging are important tools to evaluate candidacy for newer therapeutic options such as poly (ADP-ribose) polymerase inhibitors, alone or in combination with androgen receptor pathway inhibitors, and [177Lu]Lu-PSMA-617. This article provides an overview of the evolving treatment landscape of mCRPC, discussing guideline-recommended treatment options and data from key clinical trials, while highlighting ongoing trials that may impact the future treatment landscape. Recommendations for optimal treatment sequencing based on individual patient factors are provided.

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

Prognostic Role of PSMA-Targeted Imaging in Metastatic Castration-Resistant Prostate Cancer: An Overview.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC.

Progression of vertebral fractures in metastatic melanoma and non-small cell lung cancer patients given immune checkpoint inhibitors

IntroductionThe immune system mediates important effects on bone metabolism, but little has been done to understand immunotherapy’s role in this interaction. This study aims to describe and identify risk factors for the occurrence and/or exacerbation of vertebral fractures (vertebral fracture progression) during immune checkpoint inhibitors (ICIs). MethodsWe conducted an observational, retrospective, monocentric study. We collected data on melanoma and NSCLC patients, treated with first-line ICIs at the Medical Oncology Department ASST Spedali Civili of Brescia, between January 2015 and November 2021, and with a median follow-up of 20.1 (6–36) months. We collected data on patients, diseases, immune-related adverse events, and cortico-steroid therapy initiated on concomitant ICIs. ResultsWe identified 135 patients, 65 (48.2 %) with locally advanced/metastatic melanoma and 70 (51.8 %) with locally advanced/metastatic non-small cell lung cancer (NSCLC). Twenty-one (15.6 %) patients already had an asymptomatic vertebral fracture at baseline before starting ICIs in monotherapy. A total of ten patients, or 7.4 %, had a vertebra fracture progression defined as a new vertebral fracture or a worsening of a previous fracture. There was a strong relation between the steroid therapy and irAEs with vertebra fracture progression [OR (95 % CI) 8.1 (3.7–17.8) p-value < 0.001] in univariable analysis. However, only steroid therapy resulted to be an independent risk factor [8.260 (95 % CI 0.909–75.095); p-value 0.061] at the multivariable analysis. ConclusionConcurrent steroid therapy in patients receiving immunotherapy exposes them to a high risk of fractures due to skeletal fragility. The use of bone resorption inhibitors should be considered in these patients to prevent these adverse events.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers

BackgroundImmunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. MethodsWe retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. ResultsA total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74–22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). ConclusionsThe combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.

Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).

Unfortunately, not all metastatic castration resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing in prostate cancer. In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science. We argue for the widespread adoption of germline testing in all patients with prostate cancer and for somatic mutations testing in patients at the time of recurrent/metastatic disease. In this first part, we review how genomic testing is performed. We also review how to overcome certain barriers to integrate genetic and biomarker testing into clinical practice.

The role of Cabazitaxel in patients with castration-resistant and osseous metastases prostate cancer. A Hellenic Cooperative Oncology Group Phase II Study.: Cabazitaxel in mCRPC patients with osseous metastases

BackgroundCabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment. MethodsCababone was a phase II translational study that attempted to identify predictors of cabazitaxel efficacy. mCRPC with documented bone metastases were enrolled prospectively and treated with cabazitaxel 25mg/m2 every three weeks. Prostate cancer biopsies, bone marrow aspirates and blood samples were collected for translational research. ResultsSixty patients were enrolled and 59 received treatment according to protocol. Six-month progression free survival (PFS) rate was 47% (95% CI: 33% - 59%) and 12-month Overall Survival (OS) rate was 70% (95% CI: 56% - 80%). Patients with reactive hematopoiesis had improved PFS and OS with cabazitaxel treatment. Mutations in HRR genes were detected in 7 patients. ConclusionsNo differences in cabazitaxel efficacy were noted according to mutational status of HRR genes analyzed. No new safety issues were detected. In conclusion, CabaBone confirmed efficacy of cabazitaxel in mCRPC patients including the subgroup of patients with HRR mutations. Reactive hematopoiesis in bone marrow biopsies was related to improved survival warranting further investigation of bone biomarkers as predictors of cabazitaxel efficacy. Micro-AbstactCabaBone is a phase II translational study that evaluated the role of bone microenvironment and HRR genes mutations in the efficacy of cabazitaxel in mCRPC patients with bone-only disease. Study confirmed efficacy of cabazitaxel in patients independent of the presence of HRR gene mutations. Reactive hematopoiesis in bone marrow was recognized as a possible predictive and prognostic biomarker of cabazitaxel efficacy.

MO42-6 Efficacy and safety of tipiracil combined with bevacizumab in metastatic colon cancer patients: a systematic review

MO42-6 Efficacy and safety of tipiracil combined with bevacizumab in metastatic colon cancer patients: a systematic review