Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies.

BACKGROUND: Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. METHODS: Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. RESULTS: Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. CONCLUSIONS: Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03579680.

Financial Toxicity in Breast Reconstruction: The Role of the Surgeon-Patient Cost-of-Care Discussion.

The financial burden of breast cancer treatment and reconstruction is a significant concern for patients. Patient desire for preoperative cost-of-care counseling while navigating the reconstructive process remains unknown. A cross-sectional survey of women from the Love Research Army was conducted. An electronic survey was distributed to women over 18 years of age and at least 1 year after postmastectomy breast reconstruction. Descriptive statistics and multivariable modeling were used to determine desire for and occurrence of cost-of-care discussions, and factors associated with preference for such discussions. Secondary outcomes included the association of financial toxicity with desire for cost discussions. Among 839 women who responded, 620 women (74.1%) did not speak to their plastic surgeon and 480 (57.4%) did not speak to a staff member regarding costs of breast reconstruction. Of the 550 women who reported it would have been helpful to discuss costs, 315 (57.3%) were not engaged in a financial conversation initiated by a health care provider. A greater proportion of women who reported financial toxicity, compared to those who did not, would have preferred to discuss costs with their plastic surgeon (65.2% vs. 43.5%, p < 0.001) or a staff member (75.5% vs. 59.3%, p < 0.001). Among women with financial toxicity, those who had some form of insurance (private, Medicaid, Medicare, "other") were significantly more likely to prefer a cost-of-care discussion ( p < 0.001, p = 0.02, p = 0.05, p = 0.01). Financial discussions about the potential costs of breast reconstruction seldom occurred in this national cohort. Given the reported preference and unmet need for financial discussions by a majority of women, better cost transparency and communication is needed.

The Acceptance and Use of Digital Technologies for Self-Reporting Medication Safety Events After Care Transitions to Home in Patients With Cancer: Survey Study.

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.

A longitudinal mixed-methods study of pathology explanation clinics in patients with newly diagnosed localized prostate cancer.

OBJECTIVES: To characterize the role of pathology explanation clinics (PECs) in prostate cancer care and determine their impact on patients, urologic oncologists, and quality of care. METHODS: Semistructured interviews with 10 patients with newly diagnosed prostate cancer were conducted before and after a PEC pilot and at the 1- and 6-month follow-up visits. Information about participants' cancer knowledge and anxiety were collected quantitatively. Documented pathologist communications and proper review of outside biopsy slides were collected. Semistructured interviews were also completed with participating urologic oncologists following the pilot. RESULTS: Pathology explanation clinics improved participants' understanding of their diagnosis, cognitively and emotionally supporting them first in their urologic oncology visit and later in making an informed treatment decision. Mean knowledge scores were high, and a minority of participants had prostate cancer anxiety. Urologic oncologists noted improved understanding and reduced anxiety among participants, enabling nuanced conversations about prognosis and management during the visit. By ensuring review of outside biopsy slides and communication of clinically significant or unexpected diagnoses, PECs supported high-quality care and patient safety. CONCLUSIONS: In this small pilot, PECs positively affected patients with prostate cancer, their clinicians, and the overall care system. Additional studies in larger populations and diverse settings will be useful.

Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer.

BACKGROUND: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. METHODS: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. RESULTS: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. CONCLUSION: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.

Primary Care Physician and Urologist Perspectives on Optimizing Active Surveillance for Low-Risk Prostate Cancer.

PURPOSE: We conducted a study to understand primary care physician (PCP) and urologist perspectives on determinants of active surveillance care delivery for men with low-risk prostate cancer. METHODS: We conducted in-depth, semistructured, virtual interviews with a purposive sample of 19 PCPs and 15 urologists between June 2020 and March 2021. We used the behavioral theory-informed Theoretical Domains Framework to understand barriers to and facilitators of active surveillance care delivery. Interviews were recorded, transcribed, and deductively coded into framework domains and constructs by 3 independent coders. Participant recruitment continued until data saturation by group. RESULTS: Our study included 19 PCPs (9 female; 4 in community practices, 15 in academic medical centers) and 15 urologists (3 female; 5 in private practice, 3 in academic medical centers). The most commonly reported Theoretical Domains Framework domains affecting active surveillance care were (1) knowledge and (2) environmental context and resources. Although urologists were knowledgeable about active surveillance, PCPs mentioned limitations in their understanding of active surveillance (eg, what follow-up entails). Both groups noted the importance of an informed patient, especially how a patient's understanding of active surveillance facilitates their receipt of recommended follow-up. Physicians viewed patient loss to follow-up as a barrier, but identified a favorable organizational culture/climate (eg, good communication between physicians) as a facilitator. CONCLUSIONS: With patients increasingly involving their PCPs in their cancer care, our study presents factors both PCPs and urologists perceive (or identify) as affecting optimal active surveillance care delivery. We provide insights that can help inform multilevel supportive interventions for patients, physicians, and organizations to ensure the success of active surveillance as a management strategy for low-risk prostate cancer.

High expression of Trop2 is associated with aggressive localized prostate cancer and is a candidate urinary biomarker.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Patient perspectives on factors influencing active surveillance adherence for low-risk prostate cancer: A qualitative study.

BACKGROUND: Prostate cancer is the most common cancer among men in the United States. Treatment guidelines recommend active surveillance for low-risk prostate cancer, which involves monitoring for progression, to avoid or delay definitive treatments and their side effects. Despite increased uptake, adherence to surveillance remains a challenge. METHODS: We conducted semi-structured, qualitative, virtual interviews based on the Theoretical Domains Framework (TDF), with men (15) who were or had been on active surveillance for their low-risk prostate cancer in 2020. Interviews were transcribed and coded under TDF's behavioral theory-based domains. We analyzed domains related to adherence to surveillance using constructivist grounded theory to identify themes influencing decision processes in adherence. RESULTS: The TDF domains of emotion, beliefs about consequences, environmental context and resources, and social influences were most relevant to surveillance adherence-. From these four TDF domains, three themes emerged as underlying decision processes: trust in surveillance as treatment, quality of life, and experiences of self and others. Positive perceptions of these three themes supported adherence while negative perceptions contributed to non-adherence (i.e., not receiving follow-up or stopping surveillance). The relationship between the TDF domains and themes provided a theoretical process describing factors impacting active surveillance adherence for men with low-risk prostate cancer. CONCLUSIONS: Men identified key factors impacting active surveillance adherence that provide opportunities for clinical implementation and practice improvement. Future efforts should focus on multi-level interventions that foster trust in surveillance as treatment, emphasize quality of life benefits and enhance patients' interpersonal experiences while on surveillance to optimize adherence.