Faculty Bibliography

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10^-7 and GAB2, p = 2.0×10^-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Background/UNASSIGNED:The incidence and severity of coronavirus disease 19 (COVID-19) is substantially higher in men. Sex hormones may be a potential mechanism for differences in COVID-19 outcome in men and women. We hypothesized that men treated with androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19. Methods/UNASSIGNED:We conducted an observational study of male Veterans treated in the Veterans Health Administration from February 15th to July 15th, 2020. We developed a propensity score model to predict the likelihood to undergo Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. We performed multivariable logistic regression modeling adjusted with inverse probability weighting to examine the relationship between ADT and COVID-19 incidence. We conducted logistic regression analysis among COVID-19 patients to test the association between ADT and COVID-19 severity. Results/UNASSIGNED:= 0.03). Conclusion/UNASSIGNED:ADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Testosterone and androgen receptor signaling may confer increased risk for SARS-CoV-2 infection and contribute to severe COVID-19 pathophysiology in men.

BACKGROUND/UNASSIGNED:Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes. METHODS/UNASSIGNED:In a case-control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding. RESULTS/UNASSIGNED:We identified 474 men who died from COVID-19 in March-December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18-6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95-1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death. CONCLUSIONS/UNASSIGNED:The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.

OBJECTIVE:Little is known about clinicians' decision-making about decreasing active surveillance (AS) testing/converting patients to watchful waiting (WW), nor are there any guidelines. The objective of this study was to identify factors that clinicians consider when decreasing AS testing/converting to WW for men with prostate cancer. DESIGN:Exploratory qualitative study. SETTING:All participants practiced in various institutions in the USA. PARTICIPANTS:Eligible clinicians had to provide clinical care for patients with prostate cancer in the USA and speak English. Clinicians could be either urologists or radiation oncologists. Of the 24 clinicians, 83% were urologists representing 11 states, 92% were men and 62% were white. METHODS:This qualitative study used data from semi-structured interviews. Purposive sampling was used to ensure geographical variation in the USA. Data collection continued until thematic saturation was achieved. Framework analysis guided coding and identification of themes. Two researchers coded all transcripts independently, met to discuss and reached consensus. RESULTS:Interviews with clinicians demonstrated that testing or monitoring for AS or transitioning to WW is happening in practice, whether intentionally or unintentionally. Decisions to decrease AS were personalised and tailored to patients' health status. Life expectancy was the dominant factor that influenced decision, but clinicians were generally hesitant to specify an age when they would decrease AS or transition to WW. Fear that poor adherence could lead to missed progression and concerns about the medico-legal issue of not doing enough were cited as barriers to decreasing AS. CONCLUSIONS:These findings suggest that in certain situations, AS frequency is reduced or transitioned to WW, yet decisions appear to be inconsistent and there are no significant barriers. These findings could inform further areas to explore when drafting recommendations that consider patients' values and preferences when making decisions about decreasing AS/converting to WW.

BACKGROUND:Studies have demonstrated that Black men may undergo definitive prostate cancer (CaP) treatment less often than men of other races, but it is unclear whether they are avoiding overtreatment of low-risk disease or experiencing a reduction in appropriate care. The authors' aim was to assess the role of race as it relates to treatment benefit in access to CaP treatment in a single-payer population. METHODS:The authors used the Veterans Health Administration (VHA) Corporate Data Warehouse to perform a retrospective cohort study of veterans diagnosed with low- or intermediate-risk CaP between 2011 and 2017. RESULTS:The authors identified 35,427 men with incident low- or intermediate-risk CaP. When they controlled for covariates, Black men had 1.05 times the odds of receiving treatment in comparison with non-Black men (P < .001), and high-treatment-benefit men had 1.4 times the odds of receiving treatment in comparison with those in the low-treatment-benefit group (P < .001). The interaction of race and treatment benefit was significant, with Black men in the high-treatment-benefit category less likely to receive treatment than non-Black men in the same treatment category (odds ratio, 0.89; P < .001). CONCLUSIONS:Although race does appear to influence the receipt of definitive treatment in the VHA, this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high-benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group.

PURPOSE:We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS:A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS:Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS:A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

TikTok is a social network launched in 2016, which is used to create and share short videos (≤60 seconds). TikTok was the most downloaded app in the U.S. in 2018 and 2019 and is currently available in >55 countries. Similar to other social networks, TikTok users can follow other content creators and view a feed of videos. Users may associate their videos with captions and hashtags, and comment on others' videos. TikTok has 800 million total active users with >1 billion videos viewed daily.[1].