Case Of Metastatic Prostate Cancer Research Articles

Simultaneous Metastatic Involvement of Bilateral Testes and Left Spermatic Cord in Prostate Cancer Detected on 68Ga-PSMA-11 PET/CT.

Bilateral testicular involvement in prostate cancer is quite rare. It is often associated with widespread systemic disease and inadequate response to systemic therapy. We present a case of metastatic prostate cancer with bilateral testicular metastases and simultaneous involvement of the left spermatic cord detected on 68Ga-PSMA-11 PET/CT and confirmed on the histopathology of bilateral orchiectomy done for achieving the androgen deprivation status. Early detection of such unusual sites of metastases has poorer prognostic outcome and management implications.

Real-world economic burden associated with disease progression from metastatic castration-sensitive to castration-resistant prostate cancer on treatment in the United States.

The advent of next-generation imaging will likely reduce nonmetastatic prostate cancer (PC) prevalence and increase identification of metastatic prostate cancer cases, resulting in two predominant advanced stages in the metastatic setting. There is a need to characterize changes in health care resource utilization (HRU) and costs when metastatic castration-sensitive PC (mCSPC) progresses to metastatic castration-resistant PC (mCRPC) to identify value drivers from current and new treatments. To describe treatment patterns, HRU, and total health care costs among patients with mCSPC, before and after progression to mCRPC. Clinical data from the Flatiron Metastatic PC Core Registry (January 1, 2013, to December 1, 2021) and linked claims from Komodo Health (January 1, 2014, to December 1, 2021) were used to identify patients with progression from mCSPC to mCRPC (date of progression was the index date) and subsequently initiated first-line mCRPC therapy on/after January 1, 2017. Treatment patterns and all-cause/PC-related HRU and health care costs were described per-patient-per-month (PPPM), separately for no more than 12 months pre-index (mCSPC disease state) and post-index (mCRPC disease state). Costs (payer's perspective) included those for services/procedures from medical claims and costs from pharmacy claims. Continuous HRU and costs were compared between the mCSPC and mCRPC disease states using Wilcoxon signed rank tests. Among 296 patients with mCSPC progressing to mCRPC (median age 69.0 years, 60.5% White, 15.9% Black), use of systemic therapies with androgen deprivation therapy increased dramatically from 35.1% in the mCSPC disease state to 92.9% in the mCRPC disease state, and use of androgen deprivation therapy monotherapy decreased from 25.7% to 2.4%, respectively. Although 39.2% received none of these therapies in the mCSPC disease state, this proportion decreased to 4.7% after transition to mCRPC. The mean number of days with PC-related outpatient visits increased from 1.57 to 2.16 PPPM in the mCSPC and mCRPC disease states (P < 0.001). From the mCSPC to mCRPC disease states, mean all-cause total health care costs PPPM increased from $4,424 (medical costs: $2,846) to $9,717 (medical costs: $4,654), and mean PC-related total health care costs PPPM increased from $2,859 (medical costs: $1,626) to $8,012 (medical costs: $3,285; all P < 0.001). In this real-world study of patients with disease progression from mCSPC to mCRPC in US clinical practice, nearly 2-in-3 patients did not receive treatment with additional systemic therapies before progression to castration resistance. Post-progression, mean PC-related total costs increased nearly 3-fold, with a more than 2-fold increase in PC-related medical costs. Use of additional systemic therapies may delay the time and cost associated with disease progression to castration resistance.

A Case of Metastatic Prostate Cancer with Neuroendocrine Differentiation with Long-Term Survival after Multidisciplinary Therapy

A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4＋4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.

Predictors of Metastasis in 68GA-Prostate Specific Membrane Antigen Pet-CT in the Primary Staging of Prostate Cancer.

Background: The objective of this study was to investigate factors influencing Gallium 68 Prostate Specific Membrane Antigen Positron Emission Tomography (Ga68 PSMA PET-CT) uptake for primary staging in prostate cancer. Methods: Retrospective analysis was conducted on 499 non-metastatic and 243 de novo metastatic prostate cancer cases undergoing Ga68 PSMA PET-CT. Demographic, clinical, and imaging data were collected and analyzed. Multivariate logistic regression determined independent risk factors for metastasis detection on Ga68 PSMA PET-CT. Results: Metastatic cases showed higher levels of total PSA, PSA density (dPSA) and biopsy ISUP grade group compared to non-metastatic cases. Multivariate analysis identified cT2 stage and dPSA as independent predictors of metastasis detection on Ga68 PSMA PET-CT. Conclusions: Ga68 PSMA PET-CT plays a crucial role in prostate cancer staging, with identified factors such as clinical T stage and dPSA significantly impacting its diagnostic accuracy. These findings underscore the importance of Ga68 PSMA PET-CT in refining clinical staging and guiding treatment decisions for prostate cancer patients.

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aβ) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aβ oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer.

Background and Objectives: Germline DNA damage response (DDR) gene mutations correlate with increased prostate cancer (PCa) risk and a more aggressive form of the disease. DDR mutation testing is recommended for metastatic PCa cases, while eligible information about the mutations' burden in the early-stage localized PCa is still limited. This study is aimed at the prospective detection of DDR pathway mutations in cases with localized PCa and correlation with clinical, histopathological, and radiological data. A comparison to the previously assessed cohort of the advanced PCa was performed. Materials and Methods: Germline DDR gene mutations were assessed prospectively in DNA samples from 139 patients, using a five-gene panel (BRCA1, BRCA2, ATM, CHEK2, and NBN) targeted next-generation sequencing. Results: This study revealed an almost three-fold higher risk of localized PCa among mutation carriers as compared to non-carriers (OR 2.84 and 95% CI: 0.75-20.23, p = 0.16). The prevalence of germline DDR gene mutations in PCa cases was 16.8% (18/107) and they were detected only in cases with PI-RADS 4/5 lesions. BRCA1/BRCA2/ATM mutation carriers were 2.6 times more likely to have a higher (>1) cISUP grade group compared to those with a CHEK2 mutation (p = 0.27). However, the number of cISUP > 1-grade patients with a CHEK2 mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% (p = 0.047). Conclusions: The results of our study suggest the potential of genetic screening for selected DDR gene mutations for early identification of cases at risk of aggressive PCa.

Abstract B081: Biological and neighborhood-level social drivers of aggressive prostate disease among Black and White men

Abstract Introduction and study purpose: Prostate cancer (PCa) is the leading type of newly diagnosed cancer and second leading cause of cancer death in American men. Significant racial differences in PCa incidence and mortality have been long-reported in the U.S., with Black men demonstrating a disproportionately higher burden of disease compared to White men. However, some studies conducted in equal access health care settings have revealed equivalent PCa outcomes for White and Black men. Identification of early predictors of prostate disease aggressiveness is essential to avoid over-treatment of clinically favorably disease that is unlikely to progress. This study examines the independent and joint roles of biological and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing biopsy for suspicion of PCa. Methodology: A retrospective cohort study was conducted at the University Hospitals (UH) Seidman Cancer Center in Cleveland, Ohio for the period January 1, 2005-December 2022. A retrospective chart review was conducted to identify eligible men, including White and Black men undergoing transrectal ultrasound-guided biopsy whose biopsy results included the following 3 groups: (i) negative biopsy with a history of 1+ negative biopsy (-ies) and no history of prostate cancer; (ii) biopsy-detected PCa of Gleason sum 6; and (iii) biopsy-detected PCa with metastasis (-es) at initial cancer detection. Detailed clinical and biological specimen data were abstracted and quantitative proteomics analysis of biopsy tissues using mass spectrometry has been conducted at the Pacific Northwest National Laboratory (PNNL). Residential addresses were used to link each man to his census-block group Area Deprivation Index (ADI) score, as a metric of SDoHs. Students t-tests, ANOVAs and Pearson correlation analysis have been performed on the first 60 eligible subjects. Results: This study has generated the entire proteome on the first 60 eligible subjects (“Discovery cohort”) and SDoH metrics have been linked to the first 284 of 300 eligible subjects. Among the first 60 subjects, there was strong separation in proteome profiles for metastatic PCa cases but little separation of Gleason 6 and biopsy negative subjects was observed. Interesting, among the proteins that showed significant correlation with clinical group, few proteins were also significant correlated with subject race. However, several oproteins were strongly associated with SDoHs. Conclusions: Identifying new markers of cancer aggressiveness within and across race has the potential to tailor disease management and identify patients who are likely to benefit from earlier, timely treatment interventions, which will ultimately improve prostate cancer outcomes and quality of life. Upon completion of targeted proteomic analyses, we will perform multi-level modeling to predict prostate disease aggressiveness as a function of protein biomarker candidates in combination with census block group-level SDOHs. Citation Format: Jennifer Cullen, Tao Liu, Karin Rodland, Ranjini Ghosh, Anood Alfahmy, Julia Payne, Sweta Balaji, Holly Hartman, Lee Ponsky, Jonathan Shoag, Gregory MacLennan. Biological and neighborhood-level social drivers of aggressive prostate disease among Black and White men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B081.

A Case of Metastatic Prostate Cancer to the Thyroid Gland with Features of Anaplastic Thyroid Cancer

A Case of Metastatic Prostate Cancer to the Thyroid Gland with Features of Anaplastic Thyroid Cancer

Abiraterone, a rare cause of severe perioperative hypokalemia with unusual presentation as aphonia and quadriparesis: a case report

BackgroundOral Abiraterone acetate is a novel antineoplastic agent approved by the FDA for the treatment of metastatic prostate cancer. Abiraterone is an irreversible inhibitor of the 17α-hydroxylase (CYP17) enzyme complex resulting in a reduction of androgens and corticosteroids. It may cause mineralocorticoid excess syndrome; hence, it is prescribed with steroids. Here we describe a case of postoperative severe hypokalemia with unusual presentation in a patient after spine surgery in which abiraterone with prednisolone was continued preoperatively. Anesthetic concerns about the perioperative administration of abiraterone have not been reported in the literature.Case presentationAn 80-year-old male with a known case of metastatic prostate cancer was posted for spine surgery under general anesthesia. Surgery was uneventful and the patient was extubated after ensuring adequate muscle power and respiratory parameters. Postoperatively, the patient developed aphonia, quadriparesis, and respiratory distress leading to reintubation. After evaluation, severe grade 4 hypokalemia was found to be the causative factor. The patient recovered well after potassium and steroid supplementation. Low potassium and cortisol levels indicate a diagnosis of abiraterone-induced hypokalemia.ConclusionPatients on abiraterone require more stringent and vigilant monitoring of potassium and cortisol levels. In such circumstances, it might be advantageous to add additional steroids or substitute alternative steroids.

Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall.

The distinction of high-grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high-grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non-regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non-regional lymph-node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high-grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected.

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology.

Prostate cancer (PCa) has a distinct molecular signature, including characteristic chromosomal translocations, gene deletions and defective DNA damage repair mechanisms. One crucial pathway involved is homologous recombination deficiency (HRD) and it is found in almost 20% of metastatic castrate-resistant PCa (mCRPC). Inherited/germline mutations are associated with a hereditary predisposition to early PCa development and aggressive behavior. BRCA2, ATM and CHECK2 are the most frequently HRD-mutated genes. BRCA2-mutated tumors have unfavorable clinical and pathological characteristics, such as intraductal carcinoma. PARP inhibitors, due to the induction of synthetic lethality, have been therapeutically approved for mCRPC with HRD alterations. Mutations are detected in metastatic tissue, while a liquid biopsy is utilized during follow-up, recognizing acquired resistance mechanisms. The mismatch repair (MMR) pathway is another DNA repair mechanism implicated in carcinogenesis, although only 5% of metastatic PCa is affected. It is associated with aggressive disease. PD-1 inhibitors have been used in MMR-deficient tumors; thus, the MMR status should be tested in all metastatic PCa cases. A surrogate marker of defective DNA repair mechanisms is the tumor mutational burden. PDL-1 expression and intratumoral lymphocytes have ambivalent predictive value. Few experimental molecules have been so far proposed as potential biomarkers. Future research may further elucidate the role of DNA damage pathways in PCa, revealing new therapeutic targets and predictive biomarkers.

Prohibitin Links Cell Cycle, Motility and Invasion in Prostate Cancer Cells.

Prohibitin (PHB) is a tumour suppressor gene with several different molecular activities. PHB overexpression leads to G1/S-phase cell cycle arrest, and PHB represses the androgen receptor (AR) in prostate cancer cells. PHB interacts with and represses members of the E2F family in a manner that may also be AR-linked, therefore making the AR:PHB:E2F interaction axis highly complex. PHB siRNA increased the growth and metastatic potential of LNCaP mouse xenografts in vivo. Conversely, PHB ectopic cDNA overexpression affected several hundred genes in LNCaP cells. Furthermore, gene ontology analysis showed that in addition to cell cycle regulation, several members of the WNT family were significantly downregulated (WNT7B, WNT9A and WNT10B), as well as pathways for cell adhesion. Online GEO data studies showed PHB expression to be decreased in clinical cases of metastatic prostate cancer, and to be correlated with higher WNT expression in metastasis. PHB overexpression reduced prostate cancer cell migration and motility in wound-healing assays, reduced cell invasion through a Matrigel layer and reduced cellular attachment. In LNCaP cells, WNT7B, WNT9A and WNT10B expression were also upregulated by androgen treatment and downregulated by androgen antagonism, indicating a role for AR in the control of these WNT genes. However, these WNTs were strongly cell cycle regulated. E2F1 cDNA ectopic expression and PHB siRNA (both cell cycle promoting effects) increased WNT7B, WNT9A and WNT10B expression, and these genes were also upregulated as cells were released from G1 to S phase synchronisation, indicating further cell cycle regulation. Therefore, the repressive effects of PHB may inhibit AR, E2F and WNT expression and its loss may increase metastatic potential in human prostate cancer.

Metastatic Prostate Cancer Presented with Isolated Unilateral Hypoglossal Nerve Palsy: Demonstration of Clinico-radiological Correlation

Isolated unilateral hypoglossal nerve palsy (IUHNP) is rare because of its complex course and close adjacent structures. Prostate cancer is a very rare cause of hypoglossal nerve palsy and reported scarcely. We herein report the first case of metastatic prostate cancer presented with IUHNP in Korea, which shows good clinico-radiological correlation.

Cervical lymphadenopathy as initial presentation of metastatic prostate cancer: A retrospective study of five cases and literature review.

Cervical lymphadenopathy as the initial presentation of metastatic prostate cancer is particularly uncommon, and easily misdiagnosed. In the current study, we describe five cases of metastatic prostate cancer in our hospital that presented with cervical lymphadenopathy as an initial symptom. The diagnosis was confirmed by needle biopsy of the suspicious lymph nodes and the serum prostate specific antigen (PSA) levels of all patients exceeded 100 ng/ml. The five patients were treated with hormonal therapy; four received traditional hormonal therapy, including bicalutamide and goserelin; one patient received hormonal therapy that included abiraterone and goserelin. Case 1 developed into castration-resistant prostate cancer (CRPC) after 7 months and died after 12 months. Case 2 rejected regular hormonal therapy for personal reasons and died 6 months after the initial diagnosis. Case 3 was still alive at the time of writing. Case 4 was administered with abiraterone, prednisolone and goserelin; the treatment was effective and the patient has remained symptom-free for the last 24 months. Case 5 was treated with hormonal and chemotherapy but died 8 months after diagnosis. In conclusion, any elderly male presenting with cervical lymphadenopathy should be considered the possibility of prostate cancer, especially when the needle biopsy reveals adenocarcinoma. The prognosis for patients presented with cervical lymphadenopathy as the initial presentation is usually poor. Hormone therapy based on abiraterone may yield a better response in such cases.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed (“prostatic cancer”, “albumin”, “globulin”, “albumin to globulin ratio”) following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12–0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12–0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430–0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259–0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

Comprehensive assessment of anaplastic lymphoma kinase in localized and metastatic prostate cancer reveals targetable alterations.

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase with genomic and expression changes in many solid tumors. ALK inhibition is first line therapy for lung cancers with ALK alterations, and an effective therapy in other tumor types, but has not been well-studied in prostate cancer. Here, we aim to delineate the role of ALK genomic and expression changes in primary and metastatic prostate cancer. We determined ALK expression by immunohistochemistry and RNA-Seq, and genomic alterations by NGS. We assessed functional consequences of ALK overexpression and pharmacological ALK inhibition by cell proliferation and cell viability assays. Among 372 primary prostate cancer cases we identified one case with uniformly high ALK protein expression. Genomic analysis revealed a SLC45A3-ALK fusion which promoted oncogenesis in in vitro assays. We observed ALK protein expression in 5/52 (9%) of metastatic prostate cancer cases, of which 4 of 5 had neuroendocrine features. ALK-expressing neuroendocrine prostate cancer had a distinct transcriptional program, and earlier disease progression. An ALK-expressing neuroendocrine prostate cancer model was sensitive to pharmacological ALK inhibition. In summary, we found that ALK overexpression is rare in primary prostate cancer, but more frequent in metastatic prostate cancers with neuroendocrine differentiation. Further, ALK fusions similar to lung cancer are an occasional driver in prostate cancer. Our data suggest that ALK-directed therapies could be an option in selected patients with advanced prostate cancer.

HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer.

Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOXB5 and involvement of HOXB5 in neuroendocrine differentiation in PCa. Immunohistochemistry showed that 56 (43.8%) of 128 cases of localized PCa were positive for HOXB5. HOXB5-positive cases were associated with poor prostate-specific antigen recurrence-free survival after prostatectomy. Among 74 cases of metastatic PCa, 43 (58.1%) were positive for HOXB5. HOXB5 expression was higher in metastatic PCa than that in localized PCa. HOXB5 knockdown suppressed cell growth and invasion, but HOXB5 overexpression increased cell growth and invasion in PCa cell lines. Furthermore, HOXB5 regulated RET expression. Gene set enrichment analysis revealed that Nelson androgen response gene set was enriched in low HOXB5 expression group. RB1 knockout increased HOXB5 expression. Of note, additional p53 knockdown further increased HOXB5 expression in RB1 knockout cells. In silico analysis showed that HOXB5 expression was increased in neuroendocrine PCa (NEPC). These results suggest that HOXB5 may be a promising prognostic marker after prostatectomy and is involved in progression to NEPC.

Vaccines Against Different Types of Cancer: Literature Review

According to the World Health Organization, in 2018, cancer was considered the second leading cause of death in the world, corresponding to 9.6 million deaths. Faced with this situation, some alternatives to combat tumors in some organs were developed, such as immunotherapy involving vaccines. Among the vaccines already developed, Sipuleucel-T (Provenge®) can be mentioned, that has been approved by the Food and Drug Administration in 2010 for cases of metastatic prostate cancer; prophylactic bivalent and quadrivalent vaccines to human papillomavirus; the nanoparticulate liposomal RNA vaccine, the melanoma FixVac (BNT111); peptide-based vaccines, such as carcinoembryonic antigen, and those that involve antigen-loaded dendritic cells for the treatment of colorectal cancer, as well as colorectal cancer stem cell-based vaccines and, for cases of ovarian cancer, dendritic cell vaccines. In relation to breast cancer, research is aimed at both immunotherapy with dendritic cells pulsed with tumor antigens and vaccines that have a combined therapy of dendritic cells and Natural Killer cells. In general, vaccines promote the induction of helper and cytotoxic cells to thereby eliminate tumor cells. This characteristic of using dendritic cells with tumor antigens already processed and presented on the cell surface allows the questioning about the use of the term “vaccine”, since it does not correspond to conventional vaccines. Thus, the studies carried out in this area of immunotherapy, although complex and expensive, show promise in the treatment of several types of cancer, with great possibilities of positively impacting the lives of all those who suffer from the disease.

Incidence and mortality trends of metastatic prostate cancer: Surveillance, Epidemiology, and End Results database analysis.

In the past decade, prostate cancer screening decreased, raising the concern of delays in diagnosis and leading to an increase in new cases of metastatic prostate cancer. This study evaluated whether these changes may have impacted trends in metastatic prostate cancer incidence and survival. Metastatic prostate cancer diagnoses from 2008-2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 registries. Age-adjusted incidence rates per 100 000 were calculated by time periods and demographic variables. Two-year all-cause and prostate cancer-specific mortality were calculated for patients diagnosed from 2008-2014, and multivariable Cox proportional hazards models were used to evaluate the impact of demographic and clinical variables. Incidence rates of metastatic prostate cancer increased by 18% from 2008-2009 to 2014-2016 (incidence rate ratio [IRR]=1.18, 95% confidence interval [CI] 1.14-1.21). This trend was observed across multiple subgroups but was greatest in non-Hispanic Whites and patients living in counties 0-10% below poverty level. There was an overall decreased risk of all-cause and prostate cancer-specific mortality, but unmarried men and men living in counties >20% below poverty level showed statistically significant increased risk of prostate cancer-specific mortality. Non-Hispanic Whites and the wealthiest subgroups had the largest increase in incidence of metastatic prostate cancer since 2008. Despite trends of decreased risk of prostate cancer-specific mortality, we found certain populations experienced increases in mortality risk. Studies exploring the role of socioeconomic factors on screening and access to newer treatments are needed.

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada.

Simple SummaryDespite significant advancements in the treatment of metastatic prostate cancer, a validated prognostic tool for patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) is still lacking. Using population-based data from Ontario, Canada, we examined the prognostic association between common laboratory tests and survival for patients with mCSPC. These low-cost commonly available laboratory tests, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, albumin, hemoglobin, PSA decrease and PSA nadir, were significantly associated with OS. They can provide important prognostic information and should be utilized more frequently among patients with newly diagnosed mCSPC.De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.