Advanced Prostate Cancer Cases Research Articles

Case report: Squamous cell carcinoma of the prostate-a clinicopathological and genomic sequencing-based investigation

Squamous differentiation of prostate cancer, which accounts for less than 1% of all cases, is typically associated with androgen deprivation treatment (ADT) or radiotherapy. This entity is aggressive and exhibits poor prognosis due to limited response to traditional treatment. However, the underlying molecular mechanisms and etiology are not fully understood. Previous findings suggest that squamous cell differentiation may potentially arise from prostate adenocarcinoma (AC), but further validation is required to confirm this hypothesis. This paper presents a case of advanced prostate cancer with a combined histologic pattern, including keratinizing SCC and AC. The study utilized whole-exome sequencing (WES) data to analyze both subtypes and identified a significant overlap in driver gene mutations between them. This suggests that the two components shared a common origin of clones. These findings emphasize the importance of personalized clinical management for prostate SCC, and specific molecular findings can help optimize treatment strategies.

No Association of Trichomonas vaginalis Seropositivity with Advanced Prostate Cancer Risk in the Multiethnic Cohort: A Nested Case-Control Study.

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case-control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82-2.64; adjusted OR = 1.31, 95% CI 0.67-2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63-3.01; adjusted OR = 1.20, 95% CI 0.46-3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer.

Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study.

Androgen deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (PFS) at 1 year and adverse events including de novo diabetes mellitus, arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with radiographic PFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and overall survival in ADT. In addition, GWAS showed that several SNPs were associated with de novo diabetes mellitus, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.

Liquid biopsy-based targeted gene screening highlights tumor cell subtypes in patients with advanced prostate cancer.

Prostate cancer (PCa) clinical heterogeneity underscores tumor heterogeneity, which may be best defined by cell subtypes. To test if cell subtypes contributing to progression can be assessed noninvasively, we investigated whether 14 genes representing luminal, neuroendocrine, and stem cells are detectable in whole blood RNA of patients with advanced PCa. For each gene, reverse transcription quantitative polymerase chain reaction assays were first validated using RNA from PCa cell lines, and their traceability in blood was assessed in cell spiking experiments. These were next tested in blood RNA of 40 advanced PCa cases and 40 healthy controls. Expression in controls, which was low or negative, was used to define stringent thresholds for gene overexpression in patients to account for normal variation in white blood cells. Thirty-five of 40 patients overexpressed at least one gene. Patients with more genes overexpressed had a higher risk of death (hazard ratio 1.42, range 1.12-1.77). Progression on androgen receptor inhibitors was associated with overexpression of stem (odds ratio [OR] 7.74, range 1.68-35.61) and neuroendocrine (OR 13.10, range 1.24-142.34) genes, while luminal genes were associated with taxanes (OR 2.7, range 1.07-6.82). Analyses in PCa transcriptomic datasets revealed that this gene panel was most prominent in metastases of advanced disease, with diversity among patients. Collectively, these findings support the contribution of the prostate cell subtypes to disease progression. Cell-subtype specific genes are traceable in blood RNA of patients with advanced PCa and are associated with clinically relevant end points. This opens the door to minimally invasive liquid biopsies for better management of this deadly disease.

Self-care Experiences of Advanced Prostate Cancer Survivors Who Underwent Androgen Deprivation Therapy.

Androgen deprivation therapy is the primary treatment for advanced cases of prostate cancer, but its adverse effects may decrease prostate cancer survivors' quality of life. The aim of this study was to understand the self-care experiences of prostate cancer survivors before and while receiving androgen deprivation therapy. A qualitative study design with inductive content analysis was used. Semistructured interviews were conducted with 13 prostate cancer survivors in Taiwan treated with androgen deprivation therapy. Data collection and analysis proceeded simultaneously until data saturation was reached. The survivors' self-care experiences were categorized into generic categories: physical impacts, psychosocial impacts, lack of supporting information, changing lifestyle habits, coping with physical symptoms, relieving stress, and acquiring disease-related knowledge. These generic categories were then organized into 2 main categories: impacts and adjustments. This article describes the experiences of prostate cancer survivors in terms of the impacts of disease and its treatment and adjustments in self-care before and while receiving treatment. It was found that the information acquired by survivors and the adjustment strategies they used were not entirely appropriate or adequate. Healthcare providers should continually assess the self-care experiences of prostate cancer survivors receiving androgen deprivation therapy, provide them with appropriate information, and clarify their understanding. This will improve survivors' disease care-related knowledge, increase the success of their experience of self-care, alleviate their emotional distress, and strengthen their ability to adjust their self-care to cope with the impacts of the disease and its treatment.

Immunohistochemical evaluation of glutaminase expression in prostate adenocarcinoma and correlation with clinicopathologic parameters.

251 Background: Glutaminolysis plays a significant role in the metabolic reprogramming of cancer cell growth and proliferation. Glutaminase (GLS1), the rate-limiting enzyme of the glutamine pathway, is frequently dysregulated in cancer. High GLS1 expression is reported in colorectal and breast cancers and has been found to correlate with the tumor stage and disease progression. Furthermore, a new orally bioavailable glutaminase inhibitor (CB-839) is in early phase clinical trials in select tumors. The purpose of this study is to investigate the status of GLS1 expression in prostate cancer (PCa) and to correlate expression levels with clinicopathologic parameters. Methods: Radical prostatectomy samples from 154 patients with prostate adenocarcinoma were retrospectively reviewed and used to evaluate GLS1 expression by immunohistochemistry (IHC). The IHC expression score was calculated by multiplying the intensity of the stain by the proportion of cells staining; cases were then segmented into negative, low, or high expression groups. In addition, 41 samples of benign prostate tissue were used as a control. Associations between GLS1 levels and clinicopathologic parameters were analyzed by Pearson’s chi-squared and Log-rank tests. Results: GLS1 expression in the benign controls were negative, low, and high in 59%, 41%, 0% of cases, respectively, compared to 53%, 21.5%, 25.5%, respectively, in PCa (p < 0.003). Most PCa patients were age < 60 (55.8%), white (78.6%), stage T2 (52.9%), node negative (80.5%), Grade Group 3 (44%), and non-smokers (63.6%). There was no difference between GLS1 expression and age, race, Gleason score, stage, node status, and smoking status by univariate analysis. The median biochemical-progression free survival for negative, low, and high expression was 10, 9, and 10 years, respectively (p = 0.7). Conclusions: In our study, PCa samples were more likely to have GLS1 expression compared to benign controls. Although GLS1 expression did not appear to be a prognostic marker, our cohort was enriched for cases with localized disease and low-to-intermediate grade PCa. As a result, future studies are warranted to evaluate the expression levels in high grade and advanced PCa cases to determine a role for prognostic and or therapeutic implication to justify future preclinical studies with CB-839.

PSMA radioligand therapy could pose infrastructural challenges fornuclear medicine: results of a basic calculation for the capacity planning of nuclear medicine beds in the German hospital sector

With the increasing use of the Lu-177-PSMA-RLT for the treatment of advanced castrate resistant prostate cancer (mCRPC), an estimation of the necessary therapy beds in nuclear medicine departments is of great importance in the view of the high number of cases of advanced prostate cancer, and as a basis to avoid a potentially infrastructure-related bottleneck for patient care in this field. The number of therapy beds available in German nuclear medicine departments was included in a basic calculation in view of the overall potential for therapy beds to be expected in the event of a possible approval of a therapeutic agent for the Lu-177-PSMA-RLT for mCRPC patients. A potential expansion of the Lu-PSMA-therapy indications was not taken into account. The basic calculation shows for a nationwide nuclear medicine bed capacity of approx. 234 000 treatment days a relatively small bed reserve of approx. 19 000 nuclear medicine bed days, which corresponds to a reserve of 63 beds for the research question. There are regional differences in bed capacity: while for some federal states there is an under-capacity of nuclear medicine therapy beds with an approved Lu-177-PSMA-RLT, this is less the case for other federal states. This basic calculation shows that the capacity of nuclear medicine therapy beds is likely to be very well utilized with a prospectively approved therapeutic agent for Lu-177-PSMA-RLT, and could even reach its limits in some German federal states. With a prospective expansion of the range of indications or the foreseeable clinical establishment of further therapeutic radiopharmaceuticals, the number of therapy beds could represent a bottleneck factor for the comprehensive patient treatment in the medium term.

Social Jetlag and Prostate Cancer Incidence in Alberta's Tomorrow Project: A Prospective Cohort Study.

Simple SummaryDue to social obligations (e.g., school, work), people shift their sleep and activity time regardless of their sleep-wake preference. To compensate for the lack of sleep accumulated over the workdays, people tend to oversleep on a work-free day. This difference in sleep timing between workdays and free days resembles traveling across different time zones, which causes jetlag (a mild form of circadian disruption). Thus, it is named social jetlag. Social jetlag has been linked with obesity, metabolic disorders, and cardiovascular risk in previous research. This study assessed social jetlag in 7455 cancer-free men in Alberta’s Tomorrow Project and followed them for on average 9.6 years, 250 men were diagnosed with prostate cancer. The study found that the more social jetlag men experienced, the greater their prostate cancer risk was. This finding warrants future research to better understand the complex behavioral and biological pathways between social jetlag and prostate cancer risk.We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35–69 years enrolled in Alberta’s Tomorrow Project (ATP) from 2001–2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0–<1 h (from 0 to anything smaller than 1), 1–<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow-up was 9.57 years, yielding 68,499 person-years. Baseline presence of social jetlag of 1–<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (p for trend = 0.004). These associations remained after adjusting for sleep duration (p for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (p for trend = 0.003) but attenuated to null in men with intermediate (p for trend = 0.150) or late chronotype (p for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings.

Abstract D067: The REACT study: A feasibility study to develop and test the integration of a California Cancer Registry Early Case Ascertainment process via electronic pathology reporting with an online clinical trial matching tool

Abstract Background: Representation of diverse patient populations in prostate cancer clinical trials is essential to ensure that trial results are applicable to all affected men. However, underrepresentation among racial/ethnic minorities remains a critical problem in cancer research. Population-based cancer registries provide a potential platform to overcome problems with inclusion of diverse patient populations in clinical research if they are used as a source for recruitment. Methods: Leveraging the statewide implementation of electronic pathology (e-path) for cancer case identification, we performed a pilot feasibility study, REACT (Registry Early case Ascertainment process via e-path with an online Clinical Trial matching tool), within the Greater Bay Area Cancer Registry to (1) develop and test a process using e-path to rapidly identify new cases of advanced prostate cancer for potential enrollment into existing prostate cancer clinical trials; and (2) test the utility of an online clinical trial matching tool used in combination with e-path to improve matching of underrepresented patients into advanced prostate cancer clinical trials. All study materials were translated into Spanish, and a Spanish-speaking bilingual recruiter is one of two recruiters. This study will accrue 50 patients. Results: Thus far, a total of 224 cases were identified from 19 reporting facilities through e-path and 213 (92%) were sent invitation letters. We have initiated recruitment contact calls with N=101; of these, 11 were excluded due to physician-indicated contraindication, and 17 (17%) declined participation. To date, 12 patients have enrolled in the study, 10 of whom completed baseline surveys, and 4 subsequently completed follow-up surveys after using the online matching tool. The majority (N=7) of participants were NH White; of higher income, &amp;gt;$150,000 (N=6); and of higher education, &amp;gt;bachelor’s/associate degree (N=8). Nine participants indicated use of the internet to learn about prostate cancer and 4 found internet prostate-cancer related information very useful. Nine participants reported receipt of prostate cancer treatment in the past 3 months, 8 received hormonal therapy, 4 received radiation, and 2 received surgery. To assess research knowledge and attitudes, 7 indicated awareness of cancer clinical trials, 6 indicated interest in participating in clinical research, 7 held a positive and 3 held a neutral attitude towards cancer clinical trials, however 5 indicated that they would not participate in a randomized study. To assess utility of the matching tool, 2 indicated it increased their interest in participating in clinical trials. Discussion: As the study progresses, we will focus effort on recruitment of underserved patients. However, thus far, preliminary results indicate that e-path used in combination with an online clinical trial matching tool may serve as an important recruitment vehicle for prostate cancer clinical trials. Citation Format: Hala T Borno, Christine Duffy, Sylvia Zhang, Todd Golden, Zinnia Loya, Debby Oh, Anobel Odisho, Scarlett Lin Gomez. The REACT study: A feasibility study to develop and test the integration of a California Cancer Registry Early Case Ascertainment process via electronic pathology reporting with an online clinical trial matching tool [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D067.

Activating AKT1 and PIK3CA Mutations in Metastatic Castration-Resistant Prostate Cancer

BackgroundActivating mutations in AKT1 and PIK3CA are undercharacterised in metastatic castration-resistant prostate cancer (mCRPC), but are linked to activation of phosphatidylinositol 3-kinase (PI3K) signalling and sensitivity to pathway inhibitors in other cancers. ObjectiveTo determine the prevalence, genomic context, and clinical associations of AKT1/PIK3CA activating mutations in mCRPC. Design, setting, and participantsWe analysed targeted cell-free DNA (cfDNA) sequencing data from 599 metastatic prostate cancer patients with circulating tumour DNA (ctDNA) content above 2%. Outcome measurements and statistical analysisIn patients with AKT1/PIK3CA mutations, cfDNA was subjected to PTEN intron sequencing and matched diagnostic tumour tissue was analysed when possible. Results and limitationsOf the patients, 6.0% (36/599) harboured somatic clonal activating mutation(s) in AKT1 or PIK3CA. Mutant allele-specific imbalance was common. Clonal mutations in mCRPC ctDNA were typically detected in pretreatment primary tissue and were consistent across serial ctDNA collections. AKT1/PIK3CA-mutant mCRPC had fewer androgen receptor (AR) gene copies than AKT1/PIK3CA wild-type mCRPC (median 4.7 vs 10.3, p = 0.003). AKT1 mutations were mutually exclusive with PTEN alterations. Patients with and without AKT1/PIK3CA mutations showed similar clinical outcomes with standard of care treatments. A heavily pretreated mCRPC patient with an AKT1 mutation experienced a 50% decline in prostate-specific antigen with Akt inhibitor (ipatasertib) monotherapy. Ipatasertib also had a marked antitumour effect in a patient-derived xenograft harbouring an AKT1 mutation. Limitations include the inability to assess AKT1/PIK3CA correlatives in ctDNA-negative patients. ConclusionsAKT1/PIK3CA activating mutations are relatively common and delineate a distinct mCRPC molecular subtype with low-level AR copy gain. Clonal prevalence and evidence of mutant allele selection propose PI3K pathway dependency in selected patients. The use of cfDNA screening enables prospective clinical trials to test PI3K pathway inhibitors in this population. Patient summaryOf advanced prostate cancer cases, 6% have activating mutations in the genes AKT1 or PIK3CA. These mutations can be identified using a blood test and may help select patients suitable for clinical trials of phosphatidylinositol 3-kinase inhibitors.

A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study.

Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We used Lasso to further select metabolites for prediction models of adiposity measures, which we used to calculate metabolic scores representing metabolic obesity. In an independent set of 212 advanced prostate cancer cases (T3b/T4/N1/M1 or lethal during follow-up) and 212 controls, we used logistic regression to evaluate the associations between adiposity measures and metabolic scores with risk of advanced disease. All adiposity measures were associated with higher blood levels of carnitines (Pearson r range, 0.16 to 0.18) and lower levels of glutamine (r = −0.19) and glycine (r, −0.29 to −0.20), in addition to alterations in various lipids. No adiposity measure or metabolic score was associated with risk of advanced prostate cancer (e.g., odds ratio for a 5 kg/m2 increase in BMI 0.96 (95% CI: 0.73, 1.27) and BMI metabolic score 1.18 (95% CI: 0.57, 2.48)). BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. Neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer.

REACT: A feasibility study to test the integration of a cancer registry early case ascertainment process via electronic pathology reporting with an online clinical trial matching tool.

207 Background: Representation of diverse patient populations in prostate cancer clinical trials is essential to ensure results are applicable to all men. However, underrepresentation among underserved populations remains a critical problem. Population-based cancer registries provide a potential platform to overcome problems with inclusion of diverse patient populations in clinical research when used as a source for recruitment. Methods: Leveraging statewide implementation of early-case ascertainment (ECA) via electronic pathology for cancer case identification, we performed a feasibility study within the Greater Bay Area Cancer Registry to (1) test a process using ECA to identify new cases of advanced prostate cancer for potential enrollment into clinical trials and (2) test the utility of an online clinical trial matching tool to improve matching of underrepresented patients into clinical trials. All study materials were translated into Spanish, and recruiters were Spanish-speaking. Results: A total of 419 cases were identified from 19 reporting facilities through ECA and sent invitation letters; 18 cases were excluded due to physician contraindication, and 68 (16%) declined participation. All enrolled participants (N=54) completed baseline surveys. To date, 40 participants completed follow-up surveys after using the online matching tool. Most participants were White (80%), of higher income (&gt;$150,000; 41%), and college-educated (70%). Thirty-seven percent indicated awareness of cancer clinical trials, 69% stated interest in participating in clinical research, and 72% held a positive attitude towards cancer clinical trials. However, 46% indicated they would not participate in a randomized study. To assess utility of the matching tool, 65% indicated it increased their interest in participating in a clinical trial. Conclusions: ECA needs to ensure sociodemographic data are available to make it useful as a tool for clinical trials. Preliminary results indicate ECA used in combination with an online clinical trial matching tool may serve as an important recruitment vehicle for prostate cancer clinical trials.

Efficacy and outcome of holmium laser enucleation of prostate in patients with urinary retention due to advanced prostate cancer

To evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) for treating urinary retention in patients with advanced prostate cancer. Thirty-eight cases of advanced prostate cancer with urinary retention were enrolled in this retrospective study. All the 38 patients were treated with CAB as a basis. Among them, 21 cases chose HoLEP additionally (HoLEP group). Seventeen cases stuck to CAB alone (CAB group). Serum PSA level, International Prostate Symptom Score (IPSS), quality of life score (QoLs), maximal flow rate (Qmax), and post-void residual volume (PVR) at 3, 6, 12, and 18 months after treatment were comparatively analyzed. The perioperative and postoperative parameters of HoLEP were assessed. Both groups demonstrated significant improvement in IPSS, QoLs, Qmax, and PVR during follow-up. But these parameters of HoLEP group improved more rapidly, significantly, and durably than CAB group. No serious complications were observed during and after HoLEP. PSA level of patients in both groups declined dramatically after surgery. But PSA in HoLEP group showed more dramatic and continuous drop. Besides, 1 of 21 patients in HoLEP group transferred into castration-resistant prostate cancer (CRPC) at 18th month of follow-up. While in CAB group, 5 of 17 patients developed into CRPC at 12th month of follow-up (P = 0.02 < 0.05). HoLEP was minimally invasive, safe, and effective, and could serve as a palliative approach to rapidly restore the patients' urine and play a cytoreductive role in advanced PCa to improve the oncological prognosis.

2711 A Rare Cause of Hematemesis: Metastatic Prostate Cancer to the Stomach

INTRODUCTION: Prostate cancer is a malignancy that constitutes the third most common type of cancer in males. Present day its mortality rate is decreasing with better screening in the form of prostate specific antigen (PSA). The most common site of metastasis is the bone. Rarely will this form of malignancy metastasize to the gastrointestinal tract. Here we present a rare case of advanced prostate cancer with gastric metastasis. CASE DESCRIPTION/METHODS: Patient is an 81 year old male with a medical history of hypertension and prostate cancer (on anti-androgen therapy) who presented to our emergency department with altered mental status, aphasia, and left sided hemiparesis. Given his poor neurologic status and inability to maintain oxygenation the patient was intubated. Notable imaging included a computed tomography (CT) scan of the brain showing findings consistent with acute infarct of the left middle cerebral artery. Notable laboratory workup included a hemoglobin 7.8 gm/dL. Physical exam was notable for a cachectic male with left sided weakness in the left upper extremity and left lower extremity. He was then admitted to the intensive care unit (ICU) where he was noted to have an acute drop in hemoglobin to 5.0 gm/dL with coffee ground emesis. An esophagogastroduodenoscopy (EGD) was then performed which showed a large infiltrative, ulcerated, friable mass lesion with contact oozing in the gastric body along the greater curvature which was biopsied. The pathology results of the biopsy specimen returned with positive staining to prostate specific antigen (PSA) consistent with metastatic prostatic adenocarcinoma in the gastric mucosa. During his hospital course at our facility, the patient's condition worsened and his family decided to withdraw care. The patient then underwent palliative extubation and expired peacefully. DISCUSSION: There are multiple primary malignancies that have the potential for metastasis to the stomach. Of these, the most common cancers include those of the lung, breast, kidney, esophagus and finally, cancers of the head and neck. Rarely will prostate cancer present with gastric metastasis. Symptoms of metastatic lesions to the stomach mimic those of primary gastric cancers and include abdominal pain, nausea, vomiting and hematemesis. Treatment of metastatic prostate cancer is best managed with androgen deprivation therapy. If this fails, alternate treatment options include chemotherapy or immunotherapy with androgen receptor antagonists or androgen synthesis inhibitors.

Clinically, Radiologically and Biochemically Metastatic Cancer Prostate: Could be Treated without Biopsy? A Clinical Case Study and Review of Literature

Diagnosis of prostate cancer is suspected if there are abnormalities during digital rectal examination (DRE) and/or steady rising in levels of prostate specific antigen (PSA) and the confirmative diagnosis is established by histopathological confirmation of malignancy by biopsy from the prostate. A 87 years old male not diabetic nor hypertensive or other co-morbidities was well apart from mild lower back pain associated with mild irritative urinary symptoms, diagnosed clinically (DRE), radiologically and biochemically (markedly elevated PSA level) as a case of advanced prostate cancer and started treatment without biopsy by androgen deprivation therapy with other symptomatic support. After one month of treatment and then after, general conditions of the patient started to be significantly improved, the first follow-up CT showed considerable decrease of the mass size, then total non visualization of the previous prostatic mass, with marked decrease of the lymph nodal size in subsequent follow-up, PSA level decreased markedly, dropped from ≥700 ng/mL to 6.867 ng/mL, and then continued to decrease in subsequent monthly evaluations to reach 0.212 ng/mL at the last measurement after 8 months of treatment, that mean near complete radiologic and biochemical response. Treatment of advanced prostate cancer might be started without biopsy if there is high probabilities malignancy by DRE, imaging studies and significant rising in PSA levelin exceptional cases.

Bone scan index as metastatic bone disease quantifier and predictor of radium-223-dichloride biochemical response.

This work aims to assess whether the biochemical response of radium-223-dichloride treatment can be predicted based on the pretherapy bone scan, and consequently if bone scan index (BSI) and maximum lesion intensity have a place as alternatives or as complements to extent of bone disease (EOBD) scoring in predicting biochemical response to treatment. Many cases of advanced prostate cancer have evidence of bone metastasis. Accurate EOBD quantification could help predict the response to radium-223-dichloride therapy. Current EOBD score is simple to use but does not consider size, intensity or localisation of lesion BSI might be more suitable for stratification of bone metastases. Bone scans (n=20) preceding radium-223-dichloride treatment for prostate cancer were assessed retrospectively using automated BSI software (EXINI) and by assessing maximum counts per lesion. Results were then compared to total alkaline phosphatase (ALP) as a measure of biochemical response to therapy using linear regressions and to their EOBD scores using box plot analysis. Moderate correlation was found between ALP response and maximum lesion intensity (R=0.41) and BSI (R=0.46). Strong correlation (R=0.71) was found between baseline ALP and BSI and between lesion number and BSI (R=0.60). Visual assessment of EOBD score was found to correlate well with baseline ALP and maximum ALP response. BSI is a useful asset in stratification of patients with metastatic bone disease. It may also have a place in prediction of biochemical response.

Genetic counseling processes and outcomes among prostate cancer patients (ProGen).

TPS343 Background: Prostate cancer (PC) is among the leading causes of cancer mortality in males. Recent studies found 8-12% of advanced PC cases may be hereditary. Germline mutations have been reported in BRCA1/2, other DNA repair genes including ATM, CHEK2, PALB2 and DNA mismatch repair genes. Genetic testing can inform treatment decisions including drug targeting, such as PARP inhibitors for men with BRCA mutations, and checkpoint inhibitors for those with pathogenic mutations in mismatch repair genes2. Discovering a pathogenic mutation associated with increased cancer risk also prompts dissemination of this information to family, where subsequent testing can lead to risk stratification and impactful opportunities for cancer screening and prevention. It is critical that men with high risk and potentially lethal prostate cancer routinely be offered genetic testing as a component of their cancer care. Genetic counseling services are limited, and more efficient services are needed. Methods: We are investigating video education prior to genetic testing compared with in-person pretest counseling with a licensed genetic counselor (GC). ProGen is an ongoing randomized trial evaluating two distinct models of cancer genetics service delivery in 450 PC cases over a two-year period. The study is conducted in collaboration with Ambry Genetics utilizing a 67-gene cancer panel. The primary aim is analysis of the proportion and type of germline mutations identified. Secondary aims include testing uptake by arm, evaluation of distress, knowledge, satisfaction with testing services, family communication, and impact on cancer care. Results are communicated by telephone with a GC. Inclusion criteria are: potentially lethal PC (metastatic, localized with Gleason score ≥8, rising/persistent PSA after local therapy), early diagnosis (≤ 55 years), prior malignancy, and/or family history potentially indicating a hereditary cancer risk. Enrollment is 74% completed at a single institution. (NCT03328091). 1 Pritchard CC, et al. Inherited DNA‐repair gene mutations in men with metastatic prostate cancer. NEJM. 2016;375:443 2 Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. NEJM . 2015;373(18):1697-1708 Clinical trial information: NCT03328091.

Circulating 25-hydroxyvitamin D, vitamin D binding protein and risk of advanced and lethal prostate cancer.

We previously found that higher total 25-hydroxyvitamin D [25(OH)D] levels were associated with lower risk of lethal prostate cancer. However, the relationships of bioavailable 25(OH)D and vitamin D binding protein (VDBP) with risk of advanced and lethal prostate cancer are unclear. In a prospective case-control study of 156 pairs of advanced prostate cancer cases and controls, we directly measured prediagnostic circulating 25(OH)D and VDBP and calculated bioavailable 25(OH)D using a validated formula. We examined the association of bioavailable 25(OH)D and VDBP levels with risk of advanced and lethal prostate cancer and whether total 25(OH)D levels interacted with VDBP levels to affect the risk. Conditional logistic models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to total 25(OH)D (ptrend = 0.02), bioavailable 25(OH)D levels were not more strongly associated with risk of advanced prostate cancer (ptrend = 0.14). Although VDBP levels were not associated with risk of advanced prostate cancer (ptrend = 0.16), we observed an interaction between total 25(OH)D levels and VDBP levels in relation to risk of advanced prostate cancer (pinteraction = 0.03). Compared to those with total 25(OH)D levels below the median and VDBP levels above the median (at highest risk), men with both levels above the median had a multivariable-adjusted OR of 0.31 (95% CI, 0.15-0.65) for advanced prostate cancer. We observed similar results when we restricted the analyses to 116 lethal prostate cancer cases and their controls. Our data suggest that VDBP levels may modify the association between total 25(OH)D levels and risk of advanced and lethal prostate cancer.

Liquid Biopsy Potential Biomarkers in Prostate Cancer.

Prostate cancer (PCa) is the second most common cancer in men worldwide with an incidence of 14.8% and a mortality of 6.6%. Shortcomings in comprehensive medical check-ups in low- and middle-income countries lead to delayed detection of PCa and are causative of high numbers of advanced PCa cases at first diagnosis. The performance of available biomarkers is still insufficient and limited applicability, including logistical and financial burdens, impedes comprehensive implementation into health care systems. There is broad agreement on the need of new biomarkers to improve (i) early detection of PCa, (ii) risk stratification, (iii) prognosis, and (iv) treatment monitoring. This review focuses on liquid biopsy tests distinguishing high-grade significant (Gleason score (GS) ≥ 7) from low-grade indolent PCa. Available biomarkers still lack performance in risk stratification of biopsy naïve patients. However, biomarkers with highly negative predictive values may help to reduce unnecessary biopsies. Risk calculators using integrative scoring systems clearly improve decision-making for invasive prostate biopsy. Emerging biomarkers have the potential to substitute PSA and improve the overall performance of risk calculators. Until then, PSA should be used and may be replaced whenever enough evidence has accumulated for better performance of a new biomarker.

The association between plasma C-peptide concentration and the risk of prostate cancer: a nested case-control study within a Japanese population-based prospective study.

The association between plasma C-peptide concentration and prostate cancer is unclear. Inconsistency of results from previous studies motivates this study. Using the Japan Public Health Center-based Prospective study, 201 prostate cancer cases and 402 controls were matched by age, public health center area, residence, date and time of blood collection, and fasting duration before blood collection. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated by conditional logistic regression models. Out of 201 cases, 144 were localized and 48 were advanced. The overall association between median plasma C-peptide concentration and prostate cancer was not significant (OR for the highest tertile=0.81, 95% CI: 0.43-1.56, P-trend=0.54). Although stratification of prostate cancer by stage indicated different effects of plasma C-peptide on localized and advanced cases, there was no association between plasma C-peptide concentration and advanced prostate cancer (OR=2.82, 95% CI: 0.30-26.36 for the highest category, P-trend=0.37) and localized cases (OR=0.49, 95% CI: 0.23-1.04 for the highest category, P-trend=0.06) for patients fasting at the time of blood collection. The association between plasma C-peptide concentration and prostate cancer risk differed by cancer stage. Differentiation of localized and advanced prostate cancer cases is crucial when investigating the association between plasma C-peptide concentration and the risk of prostate cancer.