Terris, Martha K.

Background Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals. Methods An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation. Results There were 149 clinical trials with 59,988 participants—60.3% and 39.7% were male and female, respectively—leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, –26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials). Conclusions For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated. Lay Summary This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively. Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented. Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.

Objective To evaluate biochemical recurrence ( BCR ) patterns amongst men undergoing radical prostatectomy ( RP ) with specimens having negative ( NSM ), positive ( PSM ), and close surgical margins ( CSM ) from the Shared Equal Access Regional Cancer Hospital ( SEARCH ) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. Patients and Methods Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM , PSM , and CSM . CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate‐specific antigen ( PSA ) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR , metastases, and mortality were analysed using Cox proportional hazard models. Results Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM , 1902 (44%) had PSM , and 372 (8%) had CSM . On multivariable analysis, relative to NSM , men with CSM had a higher risk of BCR (hazard ratio [ HR ] 1.51, 95% confidence interval [ CI ] 1.25–1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM ( HR 2.09, 95% CI 1.86–2.36; P < 0.001). Metastases, prostate cancer‐specific mortality and all‐cause mortality did not differ based on margin status alone. Conclusions Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

Objectives To test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non‐metastatic (M0) castration‐resistant prostate cancer ( CRPC ), in a separate cohort. Patients and Methods We retrospectively analysed 429 bone scans of 281 patients with CRPC , with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve ( AUC ), calibration plots and decision‐curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data. Results A total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log‐transformed prostate‐specific antigen ( PSA ): hazard ratio ( HR ) 2.13; 95% confidence interval ( CI ) 1.71–2.66 ( P < 0.001) and log‐transformed PSA doubling time ( PSADT ): HR 0.53; 95% CI 0.41–0.68 ( P < 0.001). Among men with a PSA level <5 ng/ mL , the rate of positive scans was 5%. The previously developed risk table had an AUC of 0.735 to predict positive bone scan with excellent calibration, and provided additional net benefit in the decision‐curve analysis. Conclusion We have validated our previously developed table to predict the risk of a positive bone scan among men with M0/Mx CRPC . Use of this risk table may allow better tailoring of patients' scanning to identify metastases early, while minimizing over‐imaging. Regardless of PSADT , positive bone scans were rare in men with a PSA <5 ng/ mL .