The Impact of Primary Gleason Grade on Biochemical Outcome Following Brachytherapy for Hormone-Naive Gleason Score 7 Prostate Cancer

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.

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Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers

Virchows Archiv ◽

10.1007/s00428-020-02834-4 ◽

2020 ◽

Vol 477 (5) ◽

pp. 625-636

Author(s):

Katharina Möller ◽

Anna Lena Wecker ◽

Doris Höflmayer ◽

Christoph Fraune ◽

Georgia Makrypidi-Fraune ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Cell ◽

Gleason Score ◽

Biochemical Recurrence ◽

Independent Predictor ◽

Prognostic Impact ◽

Advanced Tumor Stage ◽

Heterogeneous Nuclear Ribonucleoprotein ◽

Nuclear Ribonucleoprotein ◽

The Impact

Abstract Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a ubiquitous RNA splicing factor that is overexpressed and prognostically relevant in various human cancer types. To study the impact of hnRNPA1 expression in prostate cancer, we analyzed a tissue microarray containing 17,747 clinical prostate cancer specimens by immunohistochemistry. hnRNPA1 was expressed in normal prostate glandular cells but often overexpressed in cancer cells. hnRNPA1 immunostaining was interpretable in 14,258 cancers and considered strong in 33.4%, moderate in 45.9%, weak in 15.3%, and negative in 5.4%. Moderate to strong hnRNPA1 immunostaining was strongly linked to adverse tumor features including high classical and quantitative Gleason score, lymph node metastasis, advanced tumor stage, positive surgical margin, and early biochemical recurrence (p < 0.0001 each). The prognostic impact of hnRNPA1 immunostaining was independent of established preoperatively or postoperatively available prognostic parameters (p < 0.0001). Subset analyses revealed that all these associations were strongly driven by the fraction of cancers lacking the TMPRSS2:ERG gene fusion. Comparison with other key molecular data that were earlier obtained on the same TMA showed that hnRNPA1 overexpression was linked to high levels of androgen receptor (AR) expression (p < 0.0001) as well as presence of 9 of 11 chromosomal deletions (p < 0.05 each). A strong association between hnRNPA1 upregulation and tumor cell proliferation that was independent from the Gleason score supports a role for tumor cell aggressiveness. In conclusion, hnRNPA1 overexpression is an independent predictor of poor prognosis in ERG-negative prostate cancer. hnRNPA1 measurement, either alone or in combination, might provide prognostic information in ERG-negative prostate cancer.

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Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort

European Radiology ◽

10.1007/s00330-020-07256-z ◽

2020 ◽

Cited By ~ 2

Author(s):

Francesco Giganti ◽

Armando Stabile ◽

Vasilis Stavrinides ◽

Elizabeth Osinibi ◽

Adam Retter ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Gleason Score ◽

Rank Test ◽

Gleason Grade ◽

Clinical Progression ◽

Radiological Progression ◽

Grade Group ◽

Psa Density

Abstract Objectives The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. Methods A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. Results Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53–98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1–3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4–5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density. Conclusions Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. Key Points • Patients without radiological progression on MRI (PRECISE 1–3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4–5) during AS. • Patients with radiological progression on MRI (PRECISE 4–5) during AS showed a trend to an increase in PSA density.

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The impact of neoadjuvant hormone therapy on the permanent 125I-seed brachytherapy for low- or intermediate-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.201 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 201-201

Author(s):

Ryuta Tanimoto ◽

Kensuke Bekku ◽

Shin Ebara ◽

Motoo Araki ◽

Hiroyuki Yanai ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Hormonal Therapy ◽

Low Risk ◽

Prostate Brachytherapy ◽

Intermediate Risk ◽

Neoadjuvant Hormonal Therapy ◽

T Stage ◽

Risk Prostate Cancer ◽

The Impact

201 Background: To determine whether neoadjuvant hormonal therapy improves the biochemical outcome for men with low or intermediate risk prostate cancer and undergoing permanent brachytherapy. Methods: From January 2004 to April 2011, 449 patients with low-risk (221 men) or intermediate-risk (228 men) based on NCCN guideline underwent transperineal ultrasonography-guided permanent 125I-seed brachytherapy. Of these patients, 186 received neoadjuvant hormonal therapy (NHT). The median patient age was 67 years. The median follow-up (SD) was 48 (20) months (calculated from the day of implantation). Biochemical disease-free (BDF) survival was defined using Phoenix definition. The clinical variables evaluated for BDF survival included presence of NHT, Gleason score, clinical T-stage and pretreatment PSA. Results: For all patients, the 1, 3, 5-year actuarial BDF survival rates were 99.2%, 96.2% and 90% without NHT, 100%, 97.2%, 91.0% with NHT (p=0.954). When stratified by risk group, NHT did not improve the outcome for patients at low risk (P = 0.745) or at intermediate risk (P = 0.888). The duration (<= 5 vs >5 months) or combinations (single vs combined androgen blockade) of hormonal therapy were not statistically significant in predicting biochemical recurrence. In a multivariate analysis (shown below), only the Gleason score was a strong predicting factor, while NHT as well as pretreatment PSA, T stage were insignificant. Conclusions: In patients treated by permanent prostate brachytherapy, NHT did not improve the biochemical outcome for those at low-risk or intermediate-risk features. Furthermore, the duration or combinations of hormonal therapy conferred no additional biochemical advantage. [Table: see text]

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.214 ◽

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.

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Evaluating the impact of African American ancestry among men with localized prostate cancer treated with radical prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.41 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 41-41

Author(s):

Daniel Canter ◽

Julia E. Reid ◽

Maria Latsis ◽

Margaret Variano ◽

Shams Halat ◽

...

Keyword(s):

Prostate Cancer ◽

African American ◽

Radical Prostatectomy ◽

Gleason Score ◽

Metastatic Disease ◽

Proportional Hazards ◽

Clinical Stage ◽

Cox Proportional Hazards ◽

Significant Difference ◽

The Impact

41 Background: Prostate cancer (PC) is the most common male malignancy. Prior data has suggested that African American (AA) men present with more aggressive disease relative to men of other ancestries. Here, we examined the effects of ancestry on clinical and molecular measures of disease aggressiveness as well as pathologic outcomes in men treated with radical prostatectomy (RP) for localized PC. Methods: Data was collected from patients undergoing RP at the Ochsner Clinic from 2006 to 2011. Formalin−fixed paraffin embedded biopsy tissue was analyzed for the RNA expression of 31 cell cycle progression (CCP) genes and 15 housekeeping genes to obtain a CCP score (a validated molecular measure of PC aggressiveness). Cancer of the Prostate Risk Assessment (CAPRA) scores were also determined based on clinicopathologic features at the time of diagnosis. Clinical (Gleason score, tumor stage, CAPRA score) and molecular (CCP score) measures of disease aggressiveness were compared based on ancestry (AA versus non−AA). Cox proportional hazards models were used to test association of ancestry to biochemical recurrence (BCR) and progression to metastatic disease. Fisher’s exact and Wilcoxon rank sum tests were used to compare ancestries. Results: A total of 384 patients were treated with RP, including 133 (34.8%) AA men. At the time of diagnosis, the median age was 62 years (interquartile range (IQR) 56, 66) and PSA was 5.4 ng/mL (IQR 4.2, 7.6). When compared by ancestry, there were no significant differences in biopsy Gleason score (p = 0.26), clinical stage (p = 0.27), CAPRA score (p = 0.58), or CCP score (p = 0.87). In addition, there was no significant difference in the risk of BCR between ancestries (p = 0.55). Only non−AA men progressed to metastatic disease within the ten years of follow−up. Conclusions: Contrary to prior reports, these data appears to indicate that men of AA ancestry do not necessarily present with or develop a more biologically aggressive form of PC. Although these data represents only one institution’s experience, it contains a highly robust AA population compared to prior reports. Further research is required to account for the discrepancy in the previously published literature.

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Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17582 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17582-e17582

Author(s):

Daniel Herrero Rivera ◽

Ignacio Duran ◽

Laura Marcos Kovandzic ◽

Javier Puente ◽

Begona Mellado ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Gleason Score ◽

Univariate Analysis ◽

Progression Free Survival ◽

Rank Test ◽

Genetic Constitution ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

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Advancing age and the risk of adverse pathology at radical prostatectomy in men with biopsy Gleason score 6 prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.289 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 289-289

Author(s):

Daniel Kim ◽

Ming-Hui Chen ◽

Hartwig Huland ◽

Markus Graefen ◽

Derya Tilki ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Gleason Score ◽

Specific Antigen ◽

Cancer Center ◽

Study Cohort ◽

Pathologic Features ◽

Younger Men ◽

Biopsy Gleason Score ◽

The Impact

289 Background: We evaluated the impact of age > 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age > 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age > 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p < 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- < 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age > 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age > 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.

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