bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate-specific antigen velocity and the odds of detecting gleason 8 to 10 prostate cancer at biopsy
Authors: D’Amico A. V. , Cullen J. , Chen Y. , McLeod D. G. 
Published: March 2020

4567 Background: Increased detection of high-grade prostate cancer was observed in the Prostate Cancer Prevention Trial (PCPT) in men receiving finasteride that halves prostate-specific antigen (PSA) and eliminates subsequent PSA rise from benign prostatic hyperplasia. Therefore despite doubling PSA, men receiving finasteride needed a larger PSA rise to exceed 4 ng/ml and have prostate biopsy recommended compared to placebo. We evaluated whether the PSA rise during the year before biopsy (PSA velocity) was associated with prostate cancer detection. Methods: Between 1/90 and 12/03, of 2125 prostate biopsies performed for a PSA exceeding 4 ng/ml or a nodule on digital rectal examination (DRE), prostate cancer was identified in 1418. Multivariable logistic regression analyses were performed evaluating the detection of Gleason 6 or less, 7, or 8 to 10 cancer. Covariates included the continuous variables of PSA velocity and level, number of prior negative biopsies and age and the categorical variables of ethnicity, DRE findings and family history. Results: As shown in the table , PSA velocity was only associated with Gleason 8 to 10 cancers (Adjusted Odds Ratio: 1.05 [95% Confidence Interval: 1.02 to 1.08]; p = 0.001). Age, PSA level and DRE status were associated across Gleason scores (p-values 0.005 or less), whereas family history (p-values 0.02 or less) and number of prior negative biopsies (p-values 0.01 or less) were associated with Gleason 7 or less cancers. Conclusion: PSA velocity is associated with Gleason 8 to 10 cancers at biopsy providing rationale for the PCPT results and a tool to enhance detection of clinically significant prostate cancer. [Table: see text] No significant financial relationships to disclose.
Factors influencing prostate cancer specific mortality in patients receiving delayed androgen deprivation therapy for metastasis after biochemical recurrence following radical prostatectomy
Authors: Makarov D. V. , Trock B. J. , Humphreys E. B. , Mangold L. A. , Carducci M. A. , Partin A. W. , Eisenberger M. A. , Walsh P. C. 
Published: March 2020

4571 Background: For men developing PSA failure after radical prostatectomy (RP), administration of immediate androgen deprivation therapy (ADT) has not been shown to improve survival compared to delaying ADT until evidence of metastatic disease. We evaluated factors influencing prostate cancer (PCa) specific mortality (PCSM) in a cohort of PSA era patients developing metastases after RP treated with delayed ADT. Methods: 3,658 men had RP by a single surgeon at Johns Hopkins Hospital from 4/82 until 6/05. 553 had PSA failure. 216 developed radiographically evident distant metastasis. Of these, 91 men formed the study cohort: initially treated during the PSA era (1987–2005), received ADT only after documented metastasis, and having complete data. 41 of these men died. Median failure times were estimated with the Kaplan-Meier method. Prognostic impact was estimated as the hazard ratio (HR) derived from the Cox proportional hazards model. Results: Median followup from RP was 10 yrs (range 2–18). Actuarial median failure times are: 1 yr from RP to PSA failure (range 1–11), 32 mos from PSA failure to metastasis (range 0–129), 79 mos from metastasis to death (range 7–181), and 13 yrs from RP to death (range 2–18). The following variables were significant prognostic factors for PCSM in univariate analyses: Pain at diagnosis of metastases (p < 0.01), time from RP to metastasis (p = 0.02), hematocrit at metastasis (p < 0.01) and PSADT <3 mos during the 2 years prior to metastasis (p < 0.01). A multivariable Cox proportional hazards model demonstrated the following independent predictors of PCSM: pain (HR = 10.5 p < 0.01), PSA at metastasis ≥100 ng/mL (HR = 5.3 p < 0.01) and PSADT < 3 months (HR = 7.1 p < 0.01). PSADT determined in the two years immediately after PSA failure (HR = 1.0 p = 0.37) and time from RP to bone metastasis (HR = 1.0 p = 0.80) were not independent predictors of PCSM. Conclusion: Men receiving delayed ADT for development of metastasis after RP may have a prolonged survival time (13 yrs post RP - range 2–18). Optimizing the time for ADT in these patients requires well-designed, prospective randomized studies. Our data may facilitate the selection of patients and thresholds for implementation of ADT. No significant financial relationships to disclose.
Quality of life in young men after radical prostatectomy: Results from the CaPSURE registry
Authors: Wright J. L. , Lin D. W. , Cowan J. E. , Duchane J. , Carroll P. R. , Litwin M. S. 
Published: March 2020

4576 Background: Over the past two decades, the age at diagnosis and treatment of men with prostate cancer (CaP) has steadily declined. Previous work suggests that younger men have similar or improved pathologic and clinical outcomes compared to older men. The literature on quality of life (QOL) following local treatment for CaP has primarily focused on comparing treatment modalities rather than specific age groups. This analysis explored QOL outcomes in younger men following primary curative treatment for localized prostate cancer. Methods: This was a secondary analysis of a prospectively collected cohort from the CaPSURE (Cancer of the Prostate Strategic Urologic Endeavor) registry. Men who underwent radical prostatectomy (RP) for localized disease and completed the UCLA Prostate Cancer Index (PCI) pre- and one-year post-surgery were identified. Men were grouped based on age (< 55, 55–64, ≥ 65 years). A severe decline in PCI domains from pre- to post-RP was defined as a decrease of one standard deviation from the pre-RP score. PCI scores were compared across age groups, and a multivariate model created to analyze the predictors of severe declines in PCI domains. Results: 1,143 men were identified, with 190, 526 and 427 men in the three age groups, respectively. Younger men had significantly higher mean scores one-year after RP in the urinary function (UF), urinary bother (UB) and sexual function (SF) domains of the PCI. The proportion of men with a severe decline in UF, UB and SF was not significantly different in the age groups (range 49–54%, 32–38%, 58–51% respectively). However, a severe decline in SB was more common in the youngest age group than in the oldest (54% vs. 36%, p < 0.01). With the youngest men as the reference group in the multivariate model, the oldest age group was 40% less likely to have a severe decline of SB (OR = 0.60, 95% CI 0.41–0.90, p = 0.04) but trended toward a higher risk of severe decline in UB (OR = 1.27, 95% CI 0.85–1.89, p = 0.08). Conclusions: Age predicts disease-specific QOL changes at one-year following RP. Younger men had significantly better mean UF, UB, and SF domain scores one-year after RP than did their older counterparts. Men < 55 years old are more likely than older men to experience a severe decline of sexual bother but trend toward a lower risk of a severe urinary bother. No significant financial relationships to disclose.
Patterns of primary therapy for prostate cancer in elderly men: Analysis of data from CaPSURE
Authors: Konety B. , Cowan J. , Duchane J. , Carroll P. 
Published: March 2020

4577 Background: It is generally acknowledged that men who are most likely to derive benefit from therapy for prostate cancer are those with a life expectancy of greater than 10 years. We examined the patterns of primary treatment for prostate cancer in men ≥75 years of age who would have a life expectancy of approximately 10 years. Methods: We examined data from the multi-institutional CaPSURE database on type of primary therapy received for prostate cancer in men < and ≥75 years. Primary therapy was defined as watchful waiting (WW), radical prostatectomy (RP), brachytherapy (BT), BT plus external beam radiotherapy (BT+EBRT), EBRT or primary androgen deprivation therapy (PADT). Chi square tests and multinomial logistic regression analysis were performed to identify predictors of type of primary therapy. Results: The median age of the entire population (n = 10,764) was 67 years and 18% of the dataset were patients ≥75 years. A greater proportion of patients ≥75 years were white, single, had multiple co-morbidities, had low income and low education levels and were classified as high risk (43% vs. 25%) compared to those <75 years. Men ≥75 years were more likely to have received EBRT, PADT or WW (all p < .01). In a multivariate analysis adjusted for socio-demographic factors, diagnostic risk category, and number of co-morbidities at diagnosis, patients ≥75 years were less likely to be managed with primary therapy than with WW regardless of risk category or level of co-morbidity: BT (OR 0.21, 95%CI 0.15–0.31), BT/EBRT (OR 0.21, 95%CI 0.16–0.28), EBRT (OR 0.29, 95%CI 0.22–0.37), PADT (OR 0.64, 95%CI 0.51–0.81), and RP (OR 0.01, 95%CI 0.01–0.02). Conclusions: Older patients are far more likely to received WW as primary therapy regardless of burden of co-morbidity or risk level of primary cancer. A more tailored approach to prostate cancer therapy taking into account co-morbidity and functional level to decide primary therapy may be more appropriate in elderly men. Well selected older patients with high risk disease, particularly those with low co-morbidity levels, may derive survival benefit from primary therapy other than WW. [Table: see text]
Phase I/II study of vicinium given by intravesical administration in patients with superficial transitional cell carcinoma of the bladder: Phase I results
Authors: Fitsialos D. , Seitz S. , Wiecek E. , Rasamoelisolo M. , Entwistle J. , Jewett M. , MacDonald G. C. , Glover N. 
Published: March 2020

4580 Background: Vicinium is a fusion protein comprised of a humanized scFv, specific for Ep-CAM (epithelial cell adhesion molecule), and a truncated fragment of Pseudomonas exotoxin A. Ep-CAM is highly expressed on carcinoma cells including superficial transitional cell carcinomas (TCC) of the bladder. Vicinium targets and kills Ep-CAM-positive tumors. Results from the Phase I arm of a Phase I/II trial where Vicinium was instilled into the bladders of patients with superficial TCC of the bladder showed the drug to be very well tolerated and showed promising clinical results. Methods: 64 patients with Ep-CAM positive superficial TCC of the bladder, Ta, Tis or T1, Grades 2 or 3 who were refractory or intolerant to BCG therapy were admitted into the study. Dosing comprised a minimum of 3 subjects per dose level through 12 escalating doses. Vicinium was given once/week for 6 consecutive weeks by intravesical administration into the bladder via a catheter at escalating dose levels of 0.1, 0.2, 0.33, 0.66, 1.32, 2.64, 5.28, 10.56, 13.73, 17.85, 23.2 and 30.16 mg/week. All toxicities were assessed according to the NCI CTC v3. Blood samples were collected at different times in the study to determine systemic drug exposure and to assess immunogenicity. Efficacy was explored via biopsy, cystoscopy, urine cytology and FISH. Results: Vicinium was very well tolerated at all doses. Almost all (64/65) patients were positive for the Ep-CAM antigen. Pharmacokinetic analysis showed no evidence of Vicinium in the circulation of any of the patients; however, the majority of patients developed an anti-Vicinium response. Most patients, in particular at the higher doses, showed decreased tumor cell numbers by FISH analysis by the final day of treatment with the greatest sustained effect being observed in patients with the higher percentage Ep-CAM-positive tumors. Conclusions: Vicinium dosed on a weekly basis for 6 weeks was very well tolerated at all dose levels. The early clinical benefit observed with Vicinium strongly supports its development as a promising therapy for superficial transitional cell carcinoma of the bladder. The phase II arm of the trial will confirm the safety and further assess the efficacy of Vicinium at a recommended Phase II dose. [Table: see text]
Relationship between insulin-like growth factor-1 and human testicular cancer
Authors: Kortsaris A. H. , Diamantopoulos N. , Galaktidou G. , Andreadis C. , Boutis A. L. , Zavos C. , Mouratidou D. 
Published: March 2020

4586 Background: Insulin-like growth factor (IGF) has an established role in various types of cancer inducing cellular proliferation, possessing anti-apoptotic properties, and stimulating angiogenesis. We have recently published the concept that IGF-1 system might also be implicated in the pathogenesis of testicular germ cell tumors. The present study aims to elucidate our initial concept by measuring IGF-1, IGF-binding protein (IGFBP)-3, and their molar ratio in patients with testicular cancer. Methods: We measured serum IGF-1 and IGFBP-3 using solid phase Elisa in 48 patients (mean age 31,6±8,07 years) with testicular cancer who underwent chemotherapy, and in 10 healthy male, age-matched (mean age 31.2 ± 2.54), controls. Three serum samples were obtained from patients with testicular cancer: prior to chemotherapy (baseline), before cycle 3, and 9–14 months after completion of chemotherapy. One serum sample was obtained from controls. Results: Baseline mean serum IGF-1, IGFBP-3, and molar ratio IGF-1:IGFBP-3 were 254.3 ± 242 ng/ml, 3541 ± 1740 ng/ml, and 0.293 ± 0.268 in patients, and 145.8 ± 110 ng/ml, 5440 ± 3504 ng/ml, and 0.108 ± 0.168 in controls (p = 0.048, p = 0.016, and p = 0.047, respectively). Mean IGF-1, IGFBP-3, and IGF-1:IGFBP-3 before cycle 3 were 242.4 ± 177.6 ng/ml, 3606 ± 2491 ng/ml, and 0.28 ± 0.234 (p = NS in all 3 parameters). Not all 48 patients have as yet completed chemotherapy; however, preliminary results from 10 patients show a trend for normalization in mean values of the third sample (IGF-1: 157.5 ± 129.4 ng/ml, IGFBP-3: 4500 ± 2351 ng/ml, and IGF-1:IGFBP-3: 0.141 ± 0.128), comparable to those of healthy controls. A trend for higher baseline IGF-1 values was noticed in patients with poor prognosis (n = 6, IGF-1: 367.5 ± 228.7 ng/ml) compared to those with good prognosis (n = 28, IGF-1: 211.1 ± 207.8 ng/ml). Conclusions: These results confirm our initial concept that IGF-1 system may play a significant role in testicular cancer. The trend showing that chemotherapy decreases IGF-1, IGFBP-3, and their ratio to normal, may provide evidence that these parameters can be useful surrogate markers for diagnosis and surveillance of testicular tumor growth. No significant financial relationships to disclose.
Assessment of coronary heart disease risk in testicular cancer survivors
Authors: Palmer S. C. , Carver J. , Jacobs L. , Schmitz K. H. , Fung C. , Mohler E. , Vaughn D. J. 
Published: March 2020

4592 Background: Testicular cancer survivors (TCS) who receive cisplatin-based chemotherapy (CBCT) are reported to have an increased risk of coronary heart disease (CHD) compared to chemo-naive TCS (J Clin Oncol 21:1513–1523, 2003). We hypothesized that TCS treated with CBCT would demonstrate abnormal objective measures of future CHD risk compared to chemo-naive TCS. Methods: TCS ≥ 2 years from diagnosis underwent evaluation using established objective measures predictive of future CHD risk: body mass index (BMI), Framingham relative risk (RR), flow-mediated endothelium-dependent vasodilation of the brachial artery (FMD), carotid artery intima-media thickness (IMT), serum intercellular adhesion molecule-1 (ICAM-1), and high sensitivity C-reactive protein (hs-CRP). Data were analyzed using parametric and non-parametric statistics as appropriate. Results: 30 TCS who received CBCT and 20 chemo-naive TCS were recruited. The mean age and time from diagnosis were similar between the 2 groups. Both groups demonstrated elevated BMI, increased Framingham RR, and impaired FMD, consistent with an increased risk of CHD. However, there were no statistically significant differences in these measures between the two groups. Carotid IMT, ICAM-1, and hs-CRP were not significantly abnormal and these measures also did not differ between the two groups. Conclusions: TCS demonstrate abnormal objective measures of CHD risk in both CBCT-treated and chemo-naive groups. These data suggest that behavioral interventions to modify CHD risk should target all TCS independent of chemotherapy status. All values reported are mean ± standard deviation [Table: see text] No significant financial relationships to disclose.
Fractional percentage of tumor volume removed is a predictor of outcome following cytoreductive nephrectomy for metastatic renal cell carcinoma
Authors: Collins S. , Pierorazio P. M. , McKiernan J. M. , Benson M. C. 
Published: March 2020

4599 Background: Metastatic renal cell carcinoma, (M+)RCC, is associated with poor overall survival with only 10–20% of patients alive at 2-years. The objective of this study is to determine if the fractional percentage of tumor volume (FPTV) removed at cytoreductive nephrectomy predicts disease specific survival (DSS). Methods: The Columbia Urologic Oncology Database was reviewed and 1,016 patients were identified that underwent renal surgery from 1988 to the present. A retrospective cohort of 93 patients were identified with (M+)RCC at the time of nephrectomy. The prospective database was reviewed to determine the FPTV removed and remaining following surgery. Patients were stratified to having greater or less than 90% of their cancer burden removed. Primary outcome was defined as DSS. Kaplan-Meier analysis with log-rank test was performed to determine survival advantage between groups. A Cox proportional hazard model was fit for PTR in both univariate and multivariate models. Secondary analyses were conducted to determine if the size of primary tumor affected outcome and if FPTV affected hospitalization time. Results: 63 of 77 patients had >90% of their tumor burden removed. Median follow-up time was 8.6 months. Median DSS times were calculated to be 18.8 and 3.6 months for patients with >90% and <90% PTR respectively (p < 0.001). The hazard ratio for death was 5.73 for patients with <90% of tumor removed (p < 0.001). Those with >90% removed had larger primary tumors, 10.6cm vs. 7.2cm in the <90% removed group (p = 0.01). Outcome analysis by size of primary tumor demonstrated no difference in survival. Patients with <90% removed spent 13.6% of DSS time hospitalized compared to 6.3% for those with >90% removed (p = 0.89). Conclusions: For patients with (M+)RCC, overall survival is limited but can be extended by cytoreductive nephrectomy. FPTV expected to be removed is a simple and available method to counsel patients regarding the benefits of surgical intervention. No significant financial relationships to disclose.
Cost-effectiveness of sorafenib versus best supportive care in advanced renal cell carcinoma
Authors: Gao X. , Reddy P. , Dhanda R. , Gondek K. , Yeh Y. C. , Stadler W. M. , Jonasch E. 
Published: March 2020

4604 Background: Results from the Phase III TARGETs study showed that sorafenib plus best supportive care (BSC) significantly prolonged progression-free survival (PFS) compared with BSC alone (p < 0.000001) in patients with advanced renal cell carcinoma (RCC). In addition, at a planned interim analysis, overall survival was numerically longer with sorafenib than BSC with a hazard ratio of 0.72. The objective of this study was to evaluate the cost-effectiveness of sorafenib + BSC versus BSC alone in advanced RCC from a US payer perspective. Methods: A Markov model was developed to project the lifetime survival and costs associated with sorafenib + BSC and BSC alone. The model tracked patients with advanced RCC through three disease states - PFS, progression, and death. Transition probabilities between disease states varied for each 3-month period and were obtained from the TARGETs study. Life-years gained were used as a measure of treatment effectiveness. Resource utilization included drug, administration, physician visits, monitoring, and adverse events. Costs and survival benefits were discounted annually at 3%. All costs were adjusted to 2004 US dollars. Scenario sensitivity analyses were conducted. Results: The lifetime per patient costs were $85,571 and $36,634 for sorafenib + BSC and BSC alone, respectively. The life-years gained were higher for sorafenib relative to BSC. The incremental cost-effectiveness ratio (ICER) of sorafenib + BSC versus BSC alone was $75,354 per life-year gained. The key drivers of the model results were survival after progression and PFS probabilities for both treatment groups. Sensitivity analyses showed that the model results were robust to variance in sorafenib and BSC treatment costs. Conclusions: The incremental cost-effectiveness ratio was within the established threshold that society is willing to pay (i.e., $50,000-$100,000). Therefore, sorafenib + BSC appears to be cost-effective in the management of advanced RCC. [Table: see text]
Effect of obesity on PSA density (PSAD): A new clinical predictor of prostate cancer
Authors: Garzotto M. , Mongoue-Tchokote S. , Shannon J. , Peters L. , Sokoloff M. H. , Beer T. M. , Mori M. 
Published: March 2020

4617 Background: The escalating rate of obesity in the Western world presents a diagnostic challenge when screening for prostate cancer. Increased body-mass index (BMI) disrupts the ability to effectively screen this population due to an associated decrease in serum prostate-specific antigen (PSA) levels and an increase in prostate volume. We therefore sought to understand how BMI impacts the probability of harboring prostate cancer. Methods: Data were collected on 647 referred men with a serum PSA of ≤ 10 ng/ml who underwent an ultrasound-guided prostate biopsy. Variables analyzed included: age, BMI, digital rectal exam (DRE), PSA, PSAD (i.e. PSA ÷ prostate volume), prostate volume, hypoechoic lesions on ultrasound and cancer on biopsy. A one-way ANOVA was performed to determine differences in log2 (PSAD) among BMI groups (<25 kg/m2 vs. 25–30 kg/m2 vs. >30 kg/m2). Multivariate logistic regression analysis was performed to estimate the odds-ratio (OR) and 95% confidence intervals (CI). Results: Prostate cancer was detected in 19.2 % of patients. ANOVA showed the mean PSAD to be significantly different in the three BMI groups (F value = 7.1, p = .0009). The mean PSAD significantly decreased as the BMI level increased (p = .0002). Independent pre-biopsy predictors of prostate cancer were tabulated (see below). Conclusions: Obesity was associated with a decrease in PSA density. The multivariate logistic regression revealed that the effect of PSAD on cancer detection was significantly modified by BMI. Specifically, the OR associated with a doubling of PSAD was 1.7 when BMI was <25 kg/m2 vs. 2.1 when BMI was ≥25 kg/m2). This interaction was an independent predictor of prostate cancer risk, along with DRE and ultrasound findings. These data underscore the need to consider BMI as a potential effect modifier of traditional clinical risk factors for prostate cancer. The dramatic rise in obesity in the United States makes this effect modification particularly relevant. [Table: see text] No significant financial relationships to disclose.