Higher PSA Research Articles

The impact of single positive surgical margin features on biochemical recurrence after robotic radical prostatectomy.

ABSTRACTObjective:Parameters predictive of biochemical or clinical recurrence after Radical Prostatectomy (RP) were determined as pre-treatment PSA value, pathologic tumor stage, tumor grade and presence of Positive Surgical Margin (PSM), extracapsular extension and seminal vesicle invasion and the status of pelvic lymph nodes. The aim of our study is to evaluate the effect of additional features in patients undergoing RP in our clinic.Materials and Methods:We studied 556 RP operations performed between 2009 and 2016 for prostate cancer at this clinic. Preoperative and postoperative data of the patients were retrospectively reviewed. RP specimens were examined by two pathologists specialized in this subject. Of these patients, 78 (14.02%) patients with PSM were included in the study. The pathology slides of these patients were reassessed. The length of PSM (mm), localization (apex, basis and posterolateral) and Gleason pattern at this margin was determined and statistical correlations with BCR were calculated.Results:The mean follow-up after the RP of 41 patients included in the study was 37.4 ± 13.2 months. During the follow-up period of the patients, BCR was observed in 16 patients (39.02%). No statistically significant difference was observed in age and prostate volume between the groups with and without BCR development (p > 0.05). Preoperative PSA level was found to be statistically significantly higher in the group with BCR development compared to the group without recurrence (p = 0.004). In-group comparisons in each aforementioned Gleason score groups were performed in terms of BCR development and the preoperative Gleason score in the group with development of recurrence was found to be statistically significantly higher compared to the group without recurrence (p = 0.007). The length of the surgical margin was measured as 7.4 ± 4.4 mm in the BCR-developing group and 4.7 ± 3.8 mm in the no-BCR- developing group; it was statistically significantly higher in the group with development of recurrence (p = 0.03).Conclusion:Length and location of the PSM and the Gleason score detected in the PSM region could not predict biochemical recurrence according to the results of this present study. However high preoperative PSA value is an independent prognostic factor for biochemical recurrence.

Comparison of contrast-enhanced ultrasound targeted biopsies versus standard systematic biopsies for prostate cancer detection in different PSA value groups in rural China

Objective To investigate prostate cancer detection rate of different biopsy protocols in different PSA value groups in rural China. Methods A total of 186 patients underwent contrast-enhanced ultrasound (CEUS) in order to determine the puncture target prior to biopsy were enrolled in this retrospective study. All patients underwent 12-core SB combined with CEUS-TB. The biopsy results of different biopsy protocols were compared in patients with stratification by PSA value. Results In 186 patients underwent prostate biopsy, the histopathologic results revealed prostate cancer in 117 cases (62.9%) and benign lesions in 69 cases (37.1%). The PSA 4-10ng/ml group, the prostate cancer detection rate of 8-core and 12-core method was no statistical significance. But the 12-core method was significantly higher than CEUS-TB (44.9% versus 32.7%, P = 0.01). The PSA 10-20ng/ml group, there was no statistical significance in prostate cancer detection rate between SB and CEUS-TB (50.0% versus 45.7%, P = 0.15). The PSA greater than 20ng/ml group, the prostate cancer detection rate by SB was higher than CEUS targeted biopsy, but there was no statistical significance (79.1% versus 76.9%, P = 0.15). In the overall patients, the biopsy core positive rate of CEUS-TB was significantly higher than SB (97% versus 55.5% and 28.5%, P = 0.0001). Conclusion The flexible use of SB combined with CEUS-TB can reduce the number of biopsy cores in higher PSA groups. It has clinical importance in the detection of prostate cancer in different PSA value groups in rural china.

Functional outcome and complications of palliative transurethral resection of prostate (pTURP): 5years single centre (Eastern India) experience

Background: Notable number of prostatic carcinoma patients presented with bladder outlet obstruction. Among various treatment options like antiandrogen therapy, catheterisation, laser therapy, prostatic stent and pTURP, pTURP offers expeditious relief of symptoms. As, there is paucity of literature regarding outcome and complication of pTURP in Indian context. So, author did single centre indication (of surgery) matched retrospective case control study to know functional outcomes and morbidity of pTURP in eastern Indian population.Methods: Author did retrospective review of 29 patients who underwent pTURP during study period (January 2013 to January 2018) after exclusion. Same number of TURP (for benign disease) patients were selected. Functional outcome and complications of pTURP were compared with TURP group. Author also tried to find factors associated with un-favourable outcomes.Results: Despite of older pTURP group patients, operative duration, post-operative hospital stay, post-operative catheter duration and post-op maximum urinary flow rate, were statistically similar to TURP group. However, statistically similar but clinically more complication was noted in pTURP arm in terms of failed voiding trial, incontinence and re-operation rate. One capsular tear was noted only in TURP arm. Eight patients developed unfavourable outcome (1 persistent incontinence, 5 needed re-surgery and 2 required re-catheterisation in follow up period). Higher PSA, longer operative time and hormone refractory metastatic prostatic carcinoma were found to be associated with unfavourable outcome.Conclusions: pTURP is safe and effective procedure to relieve bladder outlet obstruction. Hormone refractory status, higher PSA and prolonged operative time may be risk factors of poor outcome.

The correlation analysis of positive surgical margin and biochemical recurrence after robot-assisted laparoscopic radical prostatectomy

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP). Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected. Age was (67.5±6.9) years old; median body mass index (BMI), preoperative PSA, prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2), 15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively. The group of surgical margin was divided into negative surgical margin, apex-only PSM, base-only PSM as well as apex and base PSM. Characteristics between patients stratified by surgical margin or BCR were compared using χ2 test. The influencing factors of PSM were analyzed by logistic regression. Cox regression was used for the analysis of predictive factors of BCR. Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin. Results Of all the 190 enrolled patients, total PSM rate was 24.7% (47/190), apex-only PSM rate was 13.2 % (25/190), base-only PSM rate was 5.8% (11/190), apex and base PSM rate was 5.8 % (11/190). Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P=0.048) and pathological stage (P=0.004 ). The median follow-up period was 7.3 months (0.9-26.6 months) and BCR happened in 19.5% (37/190) patients. The rates of BCR were 15.4% (22/143), 16.0% (4/25), 27.3% (3/11) and 72.7% (8/11) in the patients with negative surgical margin, apex-only PSM, base-only PSM and both apex and base PSM respectively. Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P<0.001) or patients with apex-only PSM(P=0.002). Cox analysis indicated that higher preoperative PSA (P=0.040), higher pathological stage (P=0.041) and higher pathological Gleason score (P=0.004) were the independent predictors of BCR. PSM was not a predictive factor of BCR (P=0.257). Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM. Higher preoperative PSA, higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR. PSM may not be a predictive factor of BCR. The relationship between PSM and BCR needs further study. Key words: Prostatic neoplasms; Radical prostatectomy; Robot; Positive surgical margin; Biochemical recurrence

Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer.

Distinguishing aggressive prostate cancer from indolent disease improves personalized treatment. Although only few genetic variants are known to predispose to aggressive prostate cancer, synergistic interactions of HOXB13 G84E high-risk prostate cancer susceptibility mutation with other genetic loci remain unknown. The purpose of this study was to examine the interplay of HOXB13 rs138213197 (G84E) and CIP2A rs2278911 (R229Q) germline variants on prostate cancer risk. Genotyping was done in Finnish discovery cohort (n = 2,738) and validated in Swedish (n = 3,132) and independent Finnish (n = 1,155) prostate cancer cohorts. Expression pattern analysis was followed by functional studies in prostate cancer cell models. Interplay of HOXB13 (G84E) and CIP2A (R229Q) variants results in highest observed inherited prostate cancer risk (OR, 21.1; P = 0.000024). In addition, this synergism indicates a significant association of HOXB13 T and CIP2A T dual carriers with elevated risk for high Gleason score (OR, 2.3; P = 0.025) and worse prostate cancer-specific life expectancy (HR, 3.9; P = 0.048), and it is linked with high PSA at diagnosis (OR, 3.30; P = 0.028). Furthermore, combined high expression of HOXB13-CIP2A correlates with earlier biochemical recurrence. Finally, functional experiments showed that ectopic expression of variants stimulates prostate cancer cell growth and migration. In addition, we observed strong chromatin binding of HOXB13 at CIP2A locus and revealed that HOXB13 functionally promotes CIP2A transcription. The study is limited to retrospective Nordic cohorts. Simultaneous presence of HOXB13 T and CIP2A T alleles confers for high prostate cancer risk and aggressiveness of disease, earlier biochemical relapse, and lower disease-specific life expectancy. HOXB13 protein binds to CIP2A gene and functionally promotes CIP2A transcription.

Determinants of changes in physical activity from pre-diagnosis to post-diagnosis in a cohort of prostate cancer survivors.

Physical activity (PA) has been shown to improve quality of life and survival in cancer survivors; however, a cancer diagnosis may change PA patterns. We examine determinants of changes in meeting the PA guidelines (150min/week of moderate aerobic PA) before and after a prostate cancer diagnosis. Eight hundred and thirty prostate cancer survivors who participated in a population-based case-control study between 1997 and 2000 in Alberta, Canada, enrolled in a prospective cohort study. Past year activity levels were self-reported at diagnosis (pre-diagnosis measure) and again 2years post-diagnosis. Determinants were collected by questionnaires and medical chart abstractions. Four PA patterns were created: non-exercisers (fail to meet guidelines pre-diagnosis and post-diagnosis), adopters (fail to meet guidelines pre-diagnosis, meet guidelines post-diagnosis), maintainers (meet guidelines pre-diagnosis and post-diagnosis) and relapsers (meet guidelines pre-diagnosis, fail to meet guidelines post-diagnosis). Multinomial logistic regression analyses identified that being a non-exerciser compared to maintainer was associated with being employed, rural location, high PSA, smoking status, not attending support groups and less than average physical quality of life (QoL). Being a relapser compared to maintainer was associated with rural location and lack of friend support. Finally, being a non-exerciser compared to adopter was associated with urinary incontinence, smoking status and less than average physical and mental QoL. Demographic, health and lifestyle variables are associated with changes in meeting PA guidelines from pre-diagnosis to post-diagnosis in prostate cancer survivors. Programming should be aimed at offering interventions to help inactive survivors adopt PA and active survivors to maintain PA.

Racial Disparities in the Presentation, Early Definitive Surgical Treatment, and Mortality Among Men Diagnosed with Poorly Differentiated/Undifferentiated Non-metastatic Prostate Cancer in the USA.

To assess the influence of race on presentation of poorly differentiated/undifferentiated prostate cancer, use of radical prostatectomy (RP) as primary treatment and survival outcomes. Using the 2004-2014 files of the Surveillance, Epidemiology, and End Results (SEER) data, we identified 244,167 black and white men diagnosed with poorly differentiated/undifferentiated prostate cancer. Demographic and tumor characteristics of study patients were compared by race. Logistic regression was used to evaluate the influence of race on receipt of RP. Cox proportional hazard models were fitted to determine the impact of RP and race on cancer-specific mortality (CSM) and all-cause mortality (ACM). Compared to white men, black men were diagnosed of prostate cancer at a younger age (64.2years versus (vs) 67.5years, p < 0.0001) and presented with higher median prostate-specific antigen, PSA (24.4ng/ml vs 22.1ng/ml, p < 0.0001) but lower disease stage. Lower proportion of black men received RP compared to white men (33.9% vs 42.6%; p < 0.0001). The odds of receipt of RP were 2 times higher in white men relative to black men. The risks of CSM and ACM were over 2 times and 3 times respectively higher in patients who did not receive RP vs patients who received RP in the study population and in each race. Despite the younger age at diagnosis of poorly differentiated/undifferentiated prostate cancer and higher PSA at diagnosis in black men, white men had significantly higher odds of receipt of RP relative to black men.

The Veterans Affairs Disparity Paradox: Racial Disparities Among a Cohort of American Military Veterans with Prostate Cancer

Black men with prostate cancer have historically been found to have worse outcomes compared to other racial/ethnic groups. This finding has primarily been attributed to differences in genetics, health care access, and socioeconomic status. We sought to validate this relationship between race and prostate cancer specific mortality (PCSM) in a large national cohort of American veterans. We used a nationwide database of the Veterans Health Administration (VHA) by means of the VA Informatics and Computing Infrastructure (VINCI). Our initial query captured 82,886 patients who were diagnosed with prostate cancer from 2000 to 2015 and had received radiation therapy as part of their initial treatment. To control for possible confounders, patients who received brachytherapy, surgery, or had metastatic disease at diagnosis were excluded. Covariates included age at diagnosis, T stage, Gleason score, PSA at diagnosis, administration of ADT, Charlson Comorbidity Index (CCI) score, tobacco/alcohol history, marital status, employment status, and median income. Patients who lacked data for covariates were excluded. We compared baseline characteristics between blacks and other racial/ethnic groups with Pearson’s chi-squared and Mann-Whitney U tests. We compared PCSM and non-prostate cancer mortality (NPCM) between groups using multivariable Cox proportional hazards models. Our final study cohort included 27,753 patients, of which 8,453 (30.5%) were black. At time of diagnosis, blacks were younger (64 vs 67, p<0.001), had a higher PSA (12.6 vs 10.2, p<0.001), and were more likely to have a CCI score of 2+ (24.5% vs 19.8%, p<0.001). Additionally, they were more likely to have T1 disease (72.6% vs 62.3%, p<0.0001) and slightly more likely to receive ADT (47.5% vs 46.1%, p=0.037). Blacks were less likely to have Gleason 8+ disease (20.6% vs 22.5%, p<0.001). Controlling for potential confounders, we found improved PCSM among blacks (HR 0.86, 95% CI 0.77 to 0.97, p=0.012). Increasing age, PSA, T stage, Gleason score, and CCI score were associated with worse PCSM. In addition to improved PCSM, we also found that black patients had improved NPCM compared to other racial/ethnic groups (HR 0.812, 95% CI 0.76 to 0.87, p<0.0001). Our discovery of improved prostate cancer specific mortality and non-prostate cancer mortality among black veterans demonstrates a unique racial disparity paradox that has not been seen in the general population. Further research is required to determine if our results are driven by systematic differences in the cohort or in VHA care delivery.

68Ga-PSMA PET/CT-Guided Hypofractionated Salvage Radiation Therapy and Simultaneous Integrated Boost for PSMA-Avid Sites after Radical Prostatectomy: Safety and High PSA Response

68Ga-PSMA PET/CT-Guided Hypofractionated Salvage Radiation Therapy and Simultaneous Integrated Boost for PSMA-Avid Sites after Radical Prostatectomy: Safety and High PSA Response

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) as a Diagnostic Method for Prostate Cancer

Background: Prostate cancer is the second most common cancer among men in the world. Due to the slow growth of this cancer, its early detection can lead to definitive treatment and mortality reduction. Based on the lower diagnostic ability of conventional methods, imaging methods have been paid attention in recent years. Objectives: The aim of this study was to evaluate the value and accuracy of diffusion MRI in the prostate cancer as a diagnostic method. Methods: This was a descriptive cross-sectional study conducted in a 15-month period in patients with prostate cancer who had lower urinary tract symptoms, high PSA (higher than 4 ng/mL), or an abnormal finding in the digital rectum examination. The patients were evaluated by MRI of the whole prostate gland with T2 weighted and diffusion images. Patients’ conditions were determined by a urologist with standard 12-fold transrectal sonography-guided biopsy of the prostate. Then, by a histologic examination, healthy or cancerous tissues, Gleason score, and the positive blind numbers were determined by a pathologist. In the end, the results were compared. Results: We observed 80 patients among whom, 25 cases (31.2%) had malignancies in DW-MRI, including 22 cases that had a malignancy in biopsy and three cases whose biopsy indicated the benign pathology. MRI findings in 55 cases (68.7%) were benign (BPH, prostatitis) that in four cases, malignancy was seen in the biopsy. The sensitivity of DW-MRI was 84% and specificity was 94%, indicating a high diagnostic capability for DW-MRI. The positive and negative predictive values of DW-MRI for prostate cancer were 88% and 92%, respectively. We also observed that older age leads to the lower sensitivity of the MRI. Gleason score, PSA level, and tumor burden had a direct relationship with the accuracy of DW-MRI. However, prostate volume did not have a significant relationship with the detection of cancer in MRI. Conclusions: DW-MRI can be used for better diagnosis and staging of prostate cancer in patients with prostate lesions. Accordingly, it can upgrade cancer diagnosis in patients with negative biopsies and high suspicion of cancer.

PCN294 - THE PATIENT JOURNEY OF MEN WITH LOCALISED PROSTATE CANCER: RESULTS FROM A QUALITATIVE STUDY IN GREECE

To depict the journey of prostate cancer patients from the first symptom to diagnosis and treatment and to identify the emotional aspects of their journey. A qualitative study was performed during August – November 2017, using a semi-structured interview guide. Men with confirmed diagnosis of localized prostate Ca after 2015, who had completed treatment were eligible to participate. Participants were recruited through public and private hospital urology clinics in Attica, Greece. The interviews were recorded after participants' written consent, transcribed and content analyzed. 17 men participated in the study (mean age 67years). For 12/17 participants a high PSA level prompted them to seek medical help, whereas the rest reported having urinary problems. Prolonged intervals for seeking medical attention were reported in some cases due to fear about cancer diagnosis and treatment complications. The first consultation was with a urologist, who performed further tests and suggested prostate biopsy. Fear, panic, and anxiety were the main feelings at diagnosis. All men had a prostatectomy which was perceived as the most painful part of the treatment both physically and emotionally. 6/17 patients subsequently underwent radiation therapy. Patients reported experiencing treatment side effects, which varied in duration. These negatively impacted their self-esteem and everyday activities. None of the participants sought professional psychological help, as they reported having support from their family. Delays and complexities in the patient journey were observed mainly in the time interval until the diagnosis of prostate Ca. Both the disease and its treatment had a significant physical and emotional impact on the participants.

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors

Introduction and ObjectiveStudies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. MethodsWe recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. ResultsBlack and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. ConclusionsBlack race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Radiotherapy of prostate cancer in renal transplant recipients: single-center experience.

This study analyzed the long-term outcomes of localized prostate cancer in renal transplant recipients after radiotherapy treatment - mainly brachytherapy. We retrospectively analyzed clinical data of renal transplant recipients between 2003 and 2016 at a single tertiary center, and identified four patients with high serum PSA level during regular follow-up, 1-108 months after primary renal transplantation. The mean age of patients with detected high serum PSA level with 9.25µg/l median was 59.05 years. All four patients had functioning grafts. To prove prostate cancer, they underwent trans-rectal prostate biopsy, with no complications. Histological evaluation identified prostate adenocarcinoma (Gleason 6-7, stage T1-2cN0M0) in three patients. The biopsy in the fourth patient was negative and he therefore had trans-urethral prostate resection. Histological evaluation of resected prostate tissue revealed prostate adenocarcinoma (Gleason 7, 4+3). All patients began treatment with androgen deprivation therapy. Three patients were indicated for permanent prostate brachytherapy (BT) with iodine-125 (125I) seeds and the trans-urethral resection patient was referred for external beam radiotherapy (EBRT). After a mean follow-up of 49 months (range, 30-73), all patients, irrespective of type of radiotherapy, were in complete clinical and biochemical remission, with undetectable PSA levels. The kidney grafts remained functional, with a mean creatinine level of 99 µmol/l (range 64-123) and a glomerular filtration rate of 1.17 ml/s/1.73 m2 (range, 0.89-1.59). Radiation-induced late adverse effects were reported in two BT patients; one had clinically significant urine incontinency and the other suffered urethral stricture. Localized prostate tumor was identified in all reported patients, and all received radiotherapy plus androgen deprivation. All patients were disease-free at the time of the last follow-up. Therefore, combined BT and twelve months androgen deprivation appears both safe and effective for patients with prostate cancer after kidney transplantation.

Abstract B034: Time to treatment and overall survival among men with localized prostate cancer

Abstract Background: Prostate cancer is the second most common cancer diagnosed among men in the United States. Delays from the time of confirmed diagnosis to primary treatment are more common for prostate compared to other malignancies. The objective of this study was to investigate factors associated with time to treatment and the effect of time to treatment on overall survival among men with early-stage prostate cancer. Methods: From the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, men diagnosed with localized prostate cancer who received treatment within a year of diagnosis were selected for analysis (N=6,349). Selected men had date of diagnosis, treatment date, and mortality status as of 2012. We investigated sociodemographic and clinical factors associated with time to treatment using Cox regression. We also used Cox regression to examine the effect of time to treatment on overall survival. Covariates included Gleason score, PSA level, age at diagnosis, employment status, education level, race, marital status, and comorbidity burden. Results: The median time to treatment was 73 (IQR: 44-120) days. Demographic factors associated with longer time to treatment included being Black (adjusted hazard ratio (aHR)= 0.85, 95%CI: 0.76-0.95), having some college education (aHR= 0.91, 95%CI: 0.85-0.97), and having a baccalaureate degree or a post-baccalaureate degree (aHR= 0.89, 95% CI: 0.84-0.95). Clinical factors associated with longer time to treatment were being diagnosed at an older age (aHR= 0.86, 95%CI:0.80-0.93 for age of 70-74 years and aHR= 0.80, 95%CI: 0.74-0.87 for 75 year and older) and having an elevated PSA level (HR=0.89, 95%CI: 0.81-0.94 for third PSA quartile (6.11-9.0) and HR=0.87, 95%CI: 0.81-0.94 for fourth PSA quartile (9.0 and above). Gleason score and comorbidity burden were not associated with time to treatment. Being married (aHR=1.11, 95%CI: 1.03-1.19) and being retired (aHR=1.09, 95%CI:1.034-1.16) were associated with shorter time to treatment. After adjusting for sociodemographic and clinical characteristics, time to treatment did not have a significant effect on overall survival. Conclusions: College education, being Black, older age at diagnosis, and higher PSA levels were associated with longer time to treatment. Being married and being retired were associated with shorter time to treatment. Longer time to treatment was not associated with overall mortality among PLCO men with localized prostate cancer. Citation Format: Dudith Pierre-Victor, Paul Pinsky, Iman K. Martin, Worta McCaskill-Stevens. Time to treatment and overall survival among men with localized prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B034.

Pretreatment systemic inflammation response index as an independent prognostic indicator for prostate cancer patients treated with maximal androgen blockade

Objective To investigate the efficacy of pretreatment systemic inflammation response index (SIRI) in predicting the prognostic of prostate cancer (PCa) patients treated with maximal androgen blockade (MAB). Methods The data of 351 PCa patients who had undergone MAB as first-line therapy between January 2010 and June 2015, were retrospectively analyzed. The age of patients in our cohort ranged from 51 to 89 years old, mean 76 years old. The median value of PSA was 91.60ng/ml, ranging 0.11-1 000.00 ng/ml. 39 cases had a Gleason score of 6, 47 cases had a score of 3+ 4, 89 cases had a score of 4+ 3, 107 cases had a score of 8, and 69 cases had a score of 9-10. 158 cases had bone metastasis. Patients were categorized in two groups using a cut-off point of 1.2 as calculated by the receiver-operating curve analysis. Correlations between SIRI and clinical characteristics were analyzed. Meanwhile, univariate and multivariate cox regression analyses were performed to determine the associations of SIRI with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Results The median follow-up duration was 43.0 months, ranging 9-75 months. The disease progression occurred in 162 patients, 91 patients died, including 75 who died because of PCa at the end of the last follow-up. The differences of age, Gleason score and incidence of metastasis between low SIRI group ( 0.05). But the patients in high SIRI group had higher PSA (P=0.046). Multivariate analyses identified SIRI, Gleason score and metastasis as independent prognostic factors for PFS, CSS and OS. Conclusions Pretreatment SIRI≥1.2 was an independent predictor for poor prognosis in PCa patients treated with MAB. Key words: Prostate neoplasms; Maximal androgen blockade; Systemic inflammation response index; Prognosis

Abstract CT066: Dendritic cell based cryoimmunotherapy associates with clinical variables and changes in T-cell receptor expression in a prospective phase I trial of metastatic castration resistant prostate cancer

Abstract Interim analysis data are presented for 13 patients with metastatic castration resistant prostate cancer treated with dendritic cell based cryoimmunotherapy (CryoIT) and at least three months follow-up (FU). In CryoIT autologous immature dendritic cells (iDCs) mature in cryoablated tumor tissue and engulf tumor associated antigens and thereafter migrate to lymph nodes to instruct systemic immune attacks on heterogenous cancer cells. Primary endpoint of the trial is to investigate safety of CryoIT while secondary aims include clinical, radiological and immunological responses to treatment. Adverse events (AEs) and blood analyses were registered at all visits and imaging performed before and three months post-treatment. Norwegian regulatory authorities have approved the study. CryoIT of the prostate was performed as a freeze-thaw process under anesthesia and autologous iDCs injected after last thawing cycle. Radiologic responses according to RECISTv1.1 could categorize participants into either Group 1; stable disease (n=5) or Group 2; progressive cancer (n=4). Three patients showed mixed response and one had no follow-up imaging. Hematologic and immunologic values were evaluated according to response group. To identify peripheral blood leukocyte subsets and circulating tumor cells (CTCs), ultradeep T-cell receptor (TCR) β-chain sequences of complementarity-determining region 3, we utilized flow / mass cytometry, Cellsearch System, and TCRSafe Technology, respectively. At inclusion median age was 69 (62-73) years, BMI 25.9 (25-35), ECOG score 0 (0-1) and median PSA 8 (5-11). Group 2 demonstrated higher PSA (p=0.03), median 3.9 (IQR 2.7-6.8) and 74.6 (IQR 47.4-99.0) for Group 1 and Group 2, respectively. In total, 13 possible iDC-related AEs were reported by 10 individuals, whereof one severe and 12 mild-to-moderate, with urinary retention in seven subjects. All but one resolved by use of indwelling urinary catheter for median 8 (1-40) days. Participants with high CTC numbers (&amp;gt;5) before therapy had higher rates of progression, moderate pre-treatment CTC counts (3-5) decreased and no patient acquired CTCs after therapy. Ultradeep TCR-sequencing showed more prevalent and higher expression (&amp;gt;5-fold) of new TCR clonotypes 2-6 weeks after treatment in Group 1. The treatment seems safe and well tolerated. Higher PSA indicates more advanced disease at baseline for Group 2. The data indicate immune responses to treatment with higher increases in TCR clonotypes in radiologic stable disease. Clinical trial ID: NCT02423928. Citation Format: Liv Cecilie V. Thomsen, Alfred Honorè, Bjarte Almås, Lars A. Reisæter, Jannicke Frugård, Einar K. Kristoffersen, Guro Melve, Torjan Haslerud, Jarle Rørvik, Martin Biermann, Svein Inge Helle, Gunnar Kvalheim, Waqas Azeem, Jan Roger Olsen, Ole Johan Halvorsen, Lars Akslen, Duke K. Bahn, Klaus Pantel, Sabine Riethdorf, Haakon Ragde, Bjørn Tore Gjertsen, Anne M. Øyan, Karl-Henning Kalland, Christian Beisland. Dendritic cell based cryoimmunotherapy associates with clinical variables and changes in T-cell receptor expression in a prospective phase I trial of metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT066.

The Impact of Brachytherapy Boost on Overall Survival in Men with High Risk Prostate Cancer and a Very High PSA: Is There a PSA Ceiling?

The Impact of Brachytherapy Boost on Overall Survival in Men with High Risk Prostate Cancer and a Very High PSA: Is There a PSA Ceiling?

Does partnership status affect the quality of life of men having robotic-assisted radical prostatectomy (RARP) for localised prostate cancer?

ObjectiveTo investigate whether there are any differences in prostate cancer-specific QoL measures at baseline and at 12-months post-surgery between partnered and unpartnered men having robot-assisted radical prostatectomy (RARP) for localised prostate cancer. MethodsWe investigated differences in patient-reported outcomes using the Expanded Prostate cancer Index Composite-26 (EPIC-26) and the Clark et al. Prostate Cancer Quality of Life Scales. ResultsFive hundred and forty patients were eligible for this study, 56 of whom were unpartnered. We found few differences between partnered and unpartnered men in terms of patient-reported quality of life outcomes following RARP. In our sample of patients with a high socio-economic status, partnered men had lower 12-month postoperative EPIC sexual domain scores and clinical T-stage and were more likely to be sexually active preoperatively. Overall, our data show that men having RARP for prostate cancer have low sexual confidence, high PSA concern and a low outlook at 12-months post-RARP, irrespective of partnership status. ConclusionThe findings of this study suggest that the RARP patient could benefit from a healthcare system that assesses patient sexual outcome following prostatectomy beyond potency and ability to penetrate a partner. By remaining cognisant of other domains such as sexual intimacy, sexual confidence, masculine self-esteem, health worry, PSA concern, outlook and treatment regret, nursing staff may be able to benefit the prostatectomy patient. Where deficits in these domains are observed by the nurse, referral for specialist psychological review could be made. Whether this could work to improve sexual outcomes in men following RARP deserves further investigation.

Immunohistochemical panel to characterize canine prostate carcinomas according to aberrant p63 expression.

An unusual variant of prostate adenocarcinoma (PC) expressing nuclear p63 in secretory cells instead of the typical basal expression has been reported in men. Nevertheless, the biological behavior and clinical significance of this phenomenon is unknown. In dogs, this unusual PC subtype has not been described. In this study, p63 immunoexpression was investigated in 90 canine PCs and 20 normal prostate tissues (NT). The p63 expression pattern in luminal or basal cells was confirmed in a selected group of 26 PCs and 20 NT by immunohistochemistry and/or Western blotting assays. Eleven canine PC samples aberrantly expressing p63 (p63+) in secretory cells were compared with 15 p63 negative (p63-) cases in the context of several molecular markers (high molecular weight cytokeratin-HMWC, CK8/18, CK5, AR, PSA, chromogranin, NKX3.1, PTEN, AKT and C-MYC). P63+ samples were positive for CK5, HMWC and CK8/18 and negative for PSA, NKX3.1, PTEN and chromogranin. Five p63+ PCs were negative for AR, and the remaining six samples had low AR expression. In contrast, p63- PC showed AR and PSA positive expression in all 15 samples. Only five p63- PCs were positive for CK5. Both p63+ and p63- PC samples showed higher cytoplasmic AKT expression and nuclear C-MYC staining in comparison with normal tissues. Metastatic (N = 12) and non-metastatic (N = 14) PCs showed similar immunoexpression for all markers tested. In contrast to human PC, canine PC aberrantly expressing p63 showed higher expression levels of HMWC and CK5 and lower levels of NKX3.1. Canine p63+ PC is a very rare PC group showing a distinct phenotype compared to typical canine PC, including AR and PSA negative expression. Although in a limited number of cases, p63 expression was not associated with metastasis in canine PC, and cytoplasmic p63 expression was observed in animals with shorter survival time, similar to human PC cases.

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up.

To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen-deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet. A monocentric RP database was queried for patients initially diagnosed with T4 prostate cancer, considered primarily as inoperable because of a fixed mass defined by rectal examination in combination with high PSA level and/or large foci of biopsy confirmed undifferentiated prostate cancer. Treatment consisted of primary ADT until PSA nadir with consecutive RP. Patients underwent retropubic RP (RRP) or robot-assisted laparoscopic RP (RALP) after inductive ADT until achievement of the PSA nadir, which is in general reached after 6-7months. The intraoperative course and complications were analysed. Finally, Kaplan-Meier estimates were calculated for overall survival (OS) and prostate cancer-specific survival (PCSS). We retrospectively identified 116 patients treated between 2000 and 2014. At diagnosis, the median (range) PSA level was 37.6 (2.44-284) ng/mL. The preoperative median (range) PSA after inductive ADT was 0.73 (0.01-34) ng/mL. Thereafter, patients underwent RRP or, since 2006, RALP. The median (95% confidence interval) OS was 156 (118.9-193.1) months. The PCSS at 150months was 82%. Surgical therapy of primarily inoperable prostate cancer is feasible and safe after inductive ADT. The OS of this cohort seems comparable with results described for patients with primary operable high-risk prostate cancer.