scholarly journals Clinical Germline Testing Results of Men With Prostate Cancer: Patient-Level Factors and Implications of NCCN Guideline Expansion

2021 ◽  
pp. 533-542
Author(s):  
Samantha E. Greenberg ◽  
Trevor C. Hunt ◽  
Jacob P. Ambrose ◽  
William T. Lowrance ◽  
Christopher B. Dechet ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Disease Severity ◽  
Detection Rate ◽  
Sensitivity Analyses ◽  
Gleason Grade ◽  
Nccn Guidelines ◽  
Patient Level ◽  
The Impact ◽  
Germline Testing

PURPOSE Germline likely pathogenic or pathogenic variants (PVs) have been identified in up to 17% of men with prostate cancer (PC) and may drive disease severity or be targetable by novel therapies. National Comprehensive Cancer Network (NCCN) guidelines encouraging germline testing in metastatic PC were recently expanded to include all men with high-risk, very high-risk, or regional PC. Our aim was to assess the impact of expanded NCCN guidelines on the detection rate of germline PVs and to determine patient-level factors associated with a PV germline testing result. PATIENTS AND METHODS Men with PC underwent multigene germline genetic testing for PVs from June 2016 to December 2018, and trends were compared. The association of patient-level factors with a PV germline testing result, where ≥ 1 PV was identified, was assessed using analysis of variance and univariate logistic regression. Sensitivity analyses were limited to clinically actionable variants and those associated with disease severity or progression ( BRCA1/2 and ATM). RESULTS Of 408 men undergoing germline testing, 42 (10.3%) men had PVs and 366 (89.7%) men did not have PVs identified. The proportion of men identified with a germline PV remained stable following testing criteria expansion (9.4% v 10.6%, P = .73). No patient-level factors were significantly associated with increased odds of a PV germline testing result, including age at diagnosis, race, pretreatment prostate-specific antigen, Gleason grade group, NCCN risk group, and family history of cancer (breast and/or ovarian, prostate, or any cancer). CONCLUSION This study demonstrated a stable PV detection rate in men with PC using expanded criteria aligned to the updated NCCN testing guidelines. However, we did not find strong evidence to suggest that patient-level factors are associated with PV germline testing results. These findings support the recent expansion of NCCN germline testing guidelines in PC.

Factors associated with positive germline testing results in men with prostate cancer following NCCN guideline expansion.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 230-230
Author(s):  
Trevor Charles Hunt ◽  
Samantha Greenberg ◽  
Jacob P. Ambrose ◽  
Brock B. O'Neil ◽  
Jonathan David Tward
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
High Risk ◽  
Gleason Grade ◽  
Grade Group ◽  
Nccn Guidelines ◽  
Factors Associated ◽  
Patient Level ◽  
History Of ◽  
Germline Testing

230 Background: Pathogenic variants (PV) in genes associated with hereditary cancer risk account for over 10% of cases in men with metastatic prostate cancer (PCa). NCCN guidelines encouraging germline testing (GT) in metastatic PCa were recently expanded to include all men with high risk, very high risk, or regional PCa. Previously, we showed that the rate of PV findings did not significantly decrease after expansion of these criteria. In this study, we sought to identify factors associated with a PV finding. Methods: Men with PCa underwent multi-gene GT for PVs from April 2016 – December 2018 according to NCCN guidelines pre- (2016-17) and post-expansion (2018). The association of patient-level factors of interest with a positive GT result, where at least one PV was identified, was modeled with univariate logistic regression while overall model significance was validated with ANOVA. Results: Of 410 men undergoing GT, 44 (10.7%) positive and 366 (89.3%) negative tests resulted. Mean age at diagnosis was 62.2 years. Positive testing remained stable from 9.4% to 11.2% following guideline expansion (p=0.62). None of the patient-level factors of interest were significantly associated with increased odds of a positive GT result in any model generated. These factors included age at diagnosis, race, pretreatment PSA, Gleason grade group, NCCN risk group, and family history of cancer (breast and ovarian, prostate, any cancer). Model p-values ranged from 0.84 for Gleason grade group to 0.12 for family history of any cancer. Conclusions: Future work will need to further elucidate the role of patient-level factors in identifying men with PCa at increased risk for harboring a germline PV. Nonetheless, the lack of identification of other factors associated with positive GT results and a stable PV detection rate of roughly 10% support the recent expansion of NCCN testing guidelines. Given these findings, consideration of even broader NCCN criteria for GT may be justified.

The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Language Processing ◽  
Care Delivery ◽  
Specific Antigen ◽  
Risk Groups ◽  
Low Risk ◽  
T Stage ◽  
Risk Stratum ◽  
The Impact

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

scholarly journals The impact of pathologic staging on the long-term oncologic outcomes of patients with clinically high-risk prostate cancer

Cancer ◽  
2014 ◽  
Vol 120 (11) ◽  
pp. 1656-1662 ◽  
Author(s):  
Michael R. Abern ◽  
Martha K. Terris ◽  
William J. Aronson ◽  
Christopher J. Kane ◽  
Christopher L. Amling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Oncologic Outcomes ◽  
High Risk Prostate Cancer ◽  
Pathologic Staging ◽  
Risk Prostate Cancer ◽  
The Impact

Prostate cancer treatment disparities during the COVID-19 pandemic, lessons from a multi-institutional collaborative.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6542-6542
Author(s):  
Adrien Bernstein ◽  
Ruchika Talwar ◽  
Elizabeth A. Handorf ◽  
Kaynaat Syed ◽  
Serge Ginzburg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Safety Net ◽  
Mitigation Strategies ◽  
Categorical Variables ◽  
Gleason Grade ◽  
Grade Group ◽  
Black Patients ◽  
The Impact ◽  
White Patients

6542 Background: Minority communities have been disproportionately affected by COVID-19, however the impact of the pandemic on prostate cancer (PCa) treatment is unknown. To that end, we sought to determine the racial impact on PCa surgery during the first wave of the COVID-19 pandemic. Methods: After receiving institutional review board approval, the Pennsylvania Urologic Regional Collaborative (PURC) database was queried to evaluate practice patterns for Black and White patients with untreated non-metastatic PCa during the initial lockdown of the COVID-19 pandemic (March-May 2020) compared to prior (March-May 2019). PURC is a prospective collaborative, which includes private practice and academic institutions within both urban and rural settings including regional safety-net hospitals. As data entry was likely impacted by the pandemic, we limited our search to only practices that had data entered through June 1, 2020 (5 practice sites). We compared patient and disease characteristics by race using Fisher’s exact and Pearson’s chi-square to compare categorical variables and Wilcoxon rank sum to evaluate continuous covariates. Patients were stratified by risk factors for severe COVID-19 infection as described by the CDC. We determined the covariate-adjusted impact of year and race on surgery, using logistic regression models with a race*year interaction term. Results: 647 men with untreated non-metastatic PCa were identified, 269 during the pandemic and 378 from the year prior. During the pandemic, Black men were significantly less likely to undergo prostatectomy compared to White patients (1.3% v 25.9%;p < 0.001), despite similar COVID-19 risk-factors, biopsy Gleason grade group, and comparable surgery rates prior (17.7% vs. 19.1%;p = 0.75). White men had lower pre-biopsy PSA (7.2 vs. 8.8 vs. p = 0.04) and were older (24.4% vs. 38.2% < 60yr;p = 0.09). The regression model demonstrated an 94% decline in odds of surgery(OR = 0.06 95%CI 0.007-0.43;p = 0.006) for Black patients and increase odds of surgery for White patients (OR = 1.41 95%CI 0.89-2.21;p = 0.142), after adjusting for covariates. Changes in surgical volume varied by site (33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery, caring for a greater proportion of Black patients. Conclusions: In a large multi-institutional regional collaborative, odds of PCa surgery declined only among Black patients during the initial wave of the COVID-19 pandemic. While localized prostate cancer does not require immediate treatment, the lessons from this study illuminate systemic inequities within healthcare, likely applicable across oncology. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the pandemic in order to develop balanced mitigation strategies as viral rates continue to fluctuate.

SU-FF-T-53: The Impact of Primary Gleason Grade On Biochemical Outcome Following Brachytherapy for Hormone Naïve Gleason Score 7 Prostate Cancer

2005 ◽  
Vol 32 (6Part7) ◽  
pp. 1961-1961
Author(s):  
G Merrick ◽  
W Butler ◽  
R Galbreath ◽  
Z Allen ◽  
E Adamovich
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Gleason Grade ◽  
The Impact

A decision analytic model of prostate cancer screening using prostate-specific antigen and digital rectal exam

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5155-5155
Author(s):  
J. H. Hayes ◽  
M. J. Barry ◽  
P. W. Kantoff ◽  
J. E. Stahl
Keyword(s):  
Prostate Cancer ◽  
Life Expectancy ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Decision Analytic Model ◽  
Digital Rectal Exam ◽  
Psa Screening ◽  
The Impact

5155 Background: PSA-based screening has been widely adopted in the US although a mortality benefit has yet to be demonstrated. The disutility of screening and quality of life of men diagnosed and treated after screening are critical issues in assessing its benefit and harm. The purpose of this model is to estimate the effect of one-time screening for prostate cancer using Prostate Specific Antigen (PSA) and DRE (digital rectal exam) on life expectancy (LE) and Quality Adjusted Life Expectancy (QALE) in the context of current diagnostic and treatment practice. Methods: A semi-Markov state transition simulation describes the relevant health states. Two strategies were compared: 1) Screening - single screening PSA and DRE; 2) No Screening - patients diagnosed after developing symptoms. Markov cycle length was 1 year. Transition probabilities and utility weights were developed from review of the literature and expert opinion. Sensitivity analyses were performed on all parameters. A PSA threshold of 4 ng/mL and age 65 were used for the base case. The model was created using TreeAge software. Results: For our base case, a single screening conferred a LE benefit of 0.37 y (15.86 vs 15.49 y) and a QALE benefit of 0.20 QALYs (15.62 vs 15.42 QALYs). Predicted 10 y cancer specific survival for screen-diagnosed men was 95.7% vs SEER 97.7%. The model predicted 9.5% of screened patients would have metastatic disease at diagnosis vs 5% in SEER (4% unknown stage); in unscreened men, this rate was 18/100,000 vs 15/100,000 in SEER. Sensitivity Analyses of Utilities (SA): The single screen model was relatively insensitive to SA of utilities: a 20% single cycle toll on one-time PSA screening disutility was required to eliminate the benefit of screening. The disutility of positive PSA with negative biopsy slightly affected QALE: a toll of 0.25 QALYs decreased QALE from 15.62 to 15.61 QALYs. Conclusions: Our model reveals a modest benefit to one-time screening for prostate cancer. This one-time screening model is relatively insensitive to utility SA; however, the importance of incorporating psychological effects of PSA screening in recurrent screening is to be determined. The impact of serial screening, lead time, PSA threshold, and cost effectiveness on LE and QALE is being analyzed. No significant financial relationships to disclose.

Discordance between Oncotype Dx and Saint Gallen criteria, Adjuvant!, NCCN 2011 guidelines, and initial physician treatment recommendation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11014-e11014
Author(s):  
Allan Andresson Lima Pereira ◽  
Fernando Costa Santini ◽  
Andrea Kazumi Shimada ◽  
Ellen Caroline Nascimento ◽  
Artur Katz ◽  
...  
Keyword(s):  
High Risk ◽  
Recurrence Score ◽  
Kappa Coefficient ◽  
Oncotype Dx ◽  
Treatment Recommendation ◽  
Risk Allocation ◽  
Axillary Lymph ◽  
Curative Intent ◽  
Nccn Guidelines ◽  
The Impact

e11014 Background: The Oncotype Dx recurrence score (RS) assay quantifies the risk of distant recurrence (rDR) and its use has increased despite the lack of prospective studies. Methods: This is a cross sectional retrospective study of consecutive patients (PTS) from our institution with histologically confirmed invasive breast cancer who underwent surgery with curative intent and in whom Oncotype was performed. The main objectives were to compare (1) the predicted rDR by RS and Adjuvant! (2) Risk allocation by RS and St Gallen Criteria, (3) chemotherapy indication according to RS results and NCCN guidelines and (4) to evaluate the impact of RS results on the recommendation of adjuvant chemotherapy (aCT). Results: Between October/2006-June/2011, 74 PTS were evaluated. Forty seven (63,5%) were EC IA and all had estrogen receptor positive; axillary lymph node involvement was seen in 19 PTS (13 micro and 6 macrometastasis). The rDR by RS was low in 50 PTS (67%), intermediate in 19 (26%) and high in 5 (7%). According to Saint Gallen, 7 (9%), 51 (69%) and 14 PTS (19%) were classified as low, intermediate and high risk, respectively. There was a statistical significant discordance between risk allocation according to RS and Saint Gallen (Kappa coefficient=-0.002; p=0.971). Among the 55 node-negative PTS, there was also a statistical significant discordance between the predicted average rDR, obtained from Oncotype, and Adjuvant! with median risk of 8,5% vs 15,7%, respectively (p = 0.00001 rank sum Mann Whitney test). The NCCN 2011 would have indicated aCT to 62 PTS. Among 55 classified as low and high risk by RS, the NCCN would have indicated aCT to 46 PTS. In other words, 89% (41) of PTS who would receive aCT by NCCN were classified as low risk by RS, with a statistically significant discordance (Kappa coefficient=0.035, p=0.328). Conclusions: Oncotype changed the medical management in 28 (55%) of 51 PTS in which the initial intention of the physician was known. Of these, 93% were spared aCT. We found no statistical significant concordance among the Saint Gallen, Adjuvant! or NCCN guidelines with Oncotype Dx. The rDR may be overestimated by clinicopathological-based classifications.

The influence of daily localization during treatment of prostate cancer on acute toxicity.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 214-214
Author(s):  
Peter john Rossi ◽  
Sherrie Cooper ◽  
Ashesh B. Jani
Keyword(s):  
Prostate Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Definitive Treatment ◽  
Gleason Grade ◽  
Ordered Logit ◽  
Chi Square ◽  
Logit Regression ◽  
Gu Toxicity ◽  
Gi Toxicity ◽  
The Impact

214 Background: Various localization techniques are used in clinical practice but little comparative effectivess data exists. The purpose of this investigation is to assess the impact of daily localization (L) of the prostate on toxicity during definitive treatment of prostate cancer with intensity modulated radiotherapy (IMRT). Methods: This study details an IRB approved retrospective review of three cohorts of patients treated for prostate cancer utilizing IMRT and different L technologies at four academic hospitals. Patients were treated with no technique (N), gold markers (G), or electromagnetic beacons [Calypso] (C) for daily L. Acute genitourinary (GU) and gastrointestinal (GI) toxicity was assessed according to RTOG toxicity criteria; toxicity rates between the groups were compared using the chi-square test. Ordered logit regression of all major demographic (age, race), disease (PSA, Gleason grade, and T-stage) and treatment (hormones, pelvic nodal treatment, total dose, and prior TURP) characteristics on GU and on GI toxicity were performed. Results: One hundred fifty four men who received definitive dose escalated IMRT (no brachytherapy or post-prostatectomy patients) for prostate cancer from 2006 to 2010 and were included (G: n=47; C: n=47; N: n=60). The cohorts were balanced except race (higher percentage of African Americans in the N group, due to hospital demographics) and higher grade and use of pelvic nodal treatment (which were more common in the G and C groups). Bladder V40 and V70 were higher in the N group (45.4%/24.3%) compared to C (27.9%/12.3%) and G (37.4%/18.4%) groups; however, rectal V40 and V70 were similar among all 3 groups. Toxicity results are shown in the Table; as shown the C and G groups had lower GU toxicity (p <0.001) respectively compared to the N group; no significant differences in GI toxicity were seen among the 3 groups. Ordered logit regression showed only daily L (p=0.041) reached significance in lowering GU toxicity, and only pelvic RT use (p =0.008) reached significance in increasing GI toxicity. Conclusions: In patients treated with IMRT, daily L was associated with lower acute GU toxicity but not acute GI toxicity.

Sensitivity analyses for progression-free survival (PFS) and radiographic PFS (rPFS) from the phase II STRIVE trial comparing enzalutamide (ENZA) with bicalutamide (BIC) in men with castration-resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 169-169 ◽  
Author(s):  
David F. Penson ◽  
Andrew J. Armstrong ◽  
Raoul S. Concepcion ◽  
Kenneth Wu ◽  
Fong Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Treatment Benefit ◽  
Objective Evidence ◽  
Original Definition ◽  
The Impact

169 Background: STRIVE was arandomized, double-blind, phase 2 trial comparing ENZA vs BIC in nonmetastatic (M0) or metastatic (M1) CRPC. In this study, ENZA significantly reduced the risk of prostate cancer progression or death compared with BIC in patients with M0 or M1 CRPC. Methods: 396 men with M0 (n = 139) or M1 (n = 257) CRPC were randomized to ENZA 160 mg/day or BIC 50 mg/day. The primary endpoint of PFS was defined as the time from randomization to radiographic progression, PSA progression, or death from any cause, whichever occurred first. rPFS was defined as the time from randomization to death or the first objective evidence of radiographic disease progression in soft-tissue disease per RECIST v1.1 or in bone per PCWG2 guidelines. Sensitivity analyses were prespecified to assess the impact of alternative definitions for PFS in all patients and were performed post hoc for the key secondary endpoint of rPFS in patients with M1 disease only (table). Results: Consistent with the primary analyses of PFS and rPFS, the results from all sensitivity analyses favored ENZA over BIC (table). Conclusions: PFS and rPFS sensitivity analyses in STRIVE demonstrated a consistent and robust treatment benefit with ENZA compared with BIC by any variation of the original definition of PFS. Clinical trial information: NCT01664923. [Table: see text]

Survival impact of initial local therapy selection for men under 60 with high risk prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5082-5082
Author(s):  
Adeel Kaiser ◽  
Soren Bentzen ◽  
Minhaj Siddiqui ◽  
Michael J Naslund ◽  
Young Kwok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Hormonal Therapy ◽  
Local Therapy ◽  
External Beam Radiation ◽  
Comorbidity Score ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
The Impact

5082 Background: The impact of initial local therapy selection on survival for high risk prostate cancer (PCa) patients remains uncertain. We sought to assess this effect, while limiting competing causes of death, through the examination of a younger PCa patient cohort within the National Cancer Database. Methods: We evaluated the overall survival (OS) of men under 60 with high risk PCa receiving either radiation therapy (RT) or radical prostatectomy (RP). All men in this age group were treated between 2004 and 2013, harbored cN0M0 disease, and presented with Gleason Scores (GS) of 8 to 10. The RT group included patients who received external beam radiation (EBRT) alone or EBRT in combination with brachytherapy (BT). Overall survival and covariates were evaluated using multivariable Cox regression analysis. Results: A total of 16,944 patients met inclusion criteria of which 12,155 underwent RP and 4,789 received RT as initial therapy. 82.5% of RT patients received hormonal therapy, and the median dose was 77.4 Gy. In the RP group, 17.2% of patients received postoperative radiation, and 87% of these cases received a dose exceeding 64.80 Gy. The RP group had a higher proportion of cases with Charlson-Deyo comorbidity score > 0 (15.2% v. 11.2%, p < 0.000001). At a median follow-up of 50 months (0 - 131 months), RP was associated with improved OS in comparison to RT (hazard ratio = 0.52; 95% CI (0.47, 0.58); p < 0.000001). The estimated 8-year OS (±1 standard error of the estimate) was 85.1±0.7% and 74.9±0.7%, after RP and RT, respectively. This benefit remained present when adjusting for age, year of treatment, race, comorbidity score, Gleason score, T stage, hormonal therapy, chemotherapy, form of radiation, PSA, or insurance status. Conclusions: Compared to RT, initial treatment of men under 60 with high risk PCa with RP results in a large, statistically significant improvement in overall survival that remains consistent over time and remains significant in a multivariable model adjusting for known prognostic variables. These results are limited by the retrospective nature of the database analysis, and the lack of cancer specific survival information.

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