Using Explainable Machine Learning to Explore the Impact of Synoptic Reporting on Prostate Cancer

Machine learning (ML) models have proven to be an attractive alternative to traditional statistical methods in oncology. However, they are often regarded as black boxes, hindering their adoption for answering real-life clinical questions. In this paper, we show a practical application of explainable machine learning (XML). Specifically, we explored the effect that synoptic reporting (SR; i.e., reports where data elements are presented as discrete data items) in Pathology has on the survival of a population of 14,878 Dutch prostate cancer patients. We compared the performance of a Cox Proportional Hazards model (CPH) against that of an eXtreme Gradient Boosting model (XGB) in predicting patient ranked survival. We found that the XGB model (c-index = 0.67) performed significantly better than the CPH (c-index = 0.58). Moreover, we used Shapley Additive Explanations (SHAP) values to generate a quantitative mathematical representation of how features—including usage of SR—contributed to the models’ output. The XGB model in combination with SHAP visualizations revealed interesting interaction effects between SR and the rest of the most important features. These results hint that SR has a moderate positive impact on predicted patient survival. Moreover, adding an explainability layer to predictive ML models can open their black box, making them more accessible and easier to understand by the user. This can make XML-based techniques appealing alternatives to the classical methods used in oncological research and in health care in general

Prognostic importance of concomitant non-regional lymph node and bone metastases in men with newly diagnosed metastatic prostate cancer

Objectives: To evaluate the prognostic importance of concomitant non-regional lymph node (NRLN) and bone metastases in men with synchronous metastatic hormone-sensitive prostate cancer (mHSPC), and to determine whether M1b/M1c is the most appropriate M-stage and evaluate the additional importance to the distinction in low/high volume disease. Patients and Methods: All men diagnosed with synchronous mHSPC from 2010 to 2018 in the Netherlands were identified in the Netherlands Cancer Registry. Men were categorised as having NRLN (M1a), bone (M1b), NRLN and bone (M1c), or visceral metastases (M1c). For men diagnosed since October 2015 disease volume could be determined. Analyses were performed in this cohort (>5600 men) and repeated in the 2010–2018 cohort (>14 000 men). The primary outcome measure in this observational cohort study was overall survival (OS) and Cox regression was used to calculate hazard ratios (HRs). Results: Compared to men with NRLN and bone metastases (reference group), OS of men with only NRLN (HR 0.70, 95% confidence interval [CI] 0.55–0.88) was better. This was also true for men with only bone metastases in the low-volume subgroup (HR 0.75, 95% CI0.58–0.98), but not in the high-volume subgroup (HR 0.99, 95% CI 0.84–1.18). In contrast, the OS of men with visceral metastases was worse (HR 2.20, 95% CI 1.75–2.77 + 0.97/month, 95% CI 0.96–0.98). Conclusion: In men with low-volume synchronous mHSPC, presence of concomitant NRLN and bone metastases (currently classified as M1c), is a poor prognostic sign. However, survival of men with visceral metastases (M1c) is worse. Implying that classifying concomitant NRLN and bone metastases as M1c or M1b is not appropriate. Adding a fourth M1-category to the ninth edition of the Tumour-Node-Metastasis classification should be contemplated. Furthermore, definitions of metastatic burden need to be re-evaluated

Radical prostatectomy versus external beam radiotherapy with androgen deprivation therapy for high-risk prostate cancer: a systematic review

Abstract Background To summarize recent evidence in terms of health-related quality of life (HRQoL), functional and oncological outcomes following radical prostatectomy (RP) compared to external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high-risk prostate cancer (PCa). Methods We searched Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Controlled Trial Register and the International Standard Randomized Controlled Trial Number registry on 29 march 2021. Comparative studies, published since 2016, that reported on treatment with RP versus dose-escalated EBRT and ADT for high-risk non-metastatic PCa were included. The Newcastle–Ottawa Scale was used to appraise quality and risk of bias. A qualitative synthesis was performed. Results Nineteen studies, all non-randomized, met the inclusion criteria. Risk of bias assessment indicated low (n = 14) to moderate/high (n = 5) risk of bias. Only three studies reported functional outcomes and/or HRQoL using different measurement instruments and methods. A clinically meaningful difference in HRQoL was not observed. All studies reported oncological outcomes and survival was generally good (5-year survival rates > 90%). In the majority of studies, a statistically significant difference between both treatment groups was not observed, or only differences in biochemical recurrence-free survival were reported. Conclusions Evidence clearly demonstrating superiority in terms of oncological outcomes of either RP or EBRT combined with ADT is lacking. Studies reporting functional outcomes and HRQoL are very scarce and the magnitude of the effect of RP versus dose-escalated EBRT with ADT on HRQoL and functional outcomes remains largely unknown

Impact of the COVID-19 outbreak on prostate cancer care in the Netherlands

Introduction: The COVID-19 outbreak has affected care for non-COVID diseases like cancer. We evaluated the impact of the COVID-19 outbreak on prostate cancer care in the Netherlands. Methods: Prostate cancer diagnoses per month in 2020–2021 versus 2018–2019 were compared based on preliminary data of the Netherlands Cancer Registry (NCR) and nationwide pathology network. Detailed data was retrieved from the NCR for the cohorts diagnosed from March-May 2020 (first COVID-19 wave) and March-May 2018–2019 (reference). Changes in number of diagnoses, age, disease stage and first-line treatment were compared. Results: An initial decline of 17% in prostate cancer diagnoses during the first COVID-19 wave was observed. From May onwards the number of diagnoses started to restore to approximately 95% of the expected number by the end of 2020. Stage at diagnosis remainedstable over time. In low-risk localised prostate cancer radical prostatectomy was conducted more often in week 9–12 (21% versus 12% in the reference period; OR=1.9, 95% CI; 1.2–3.1) and less active surveillance was applied (67% versus 78%; OR=0.6, 95% CI; 0.4–0.9). In the intermediate-risk group, a similar change was observed in week 13–16. Radical prostatectomy volumes in 2020 were comparable to 2018–2019. Conclusion: During the first COVID-19 wave the number of prostate cancer diagnoses declined. In the second half of 2020 this largely restored although the number remained lower than expected. Changes in treatment were temporary and compliant with adapted guidelines. Although delayed diagnoses could result in a less favourable stage distribution, possibly affecting survival, this seems not very likely

No evidence for increased mortality in SDHD variant carriers compared with the general population

Germline variants in subunit D of the succinate dehydrogenase gene (SDHD variants) are associated with an increased risk of developing paragangliomas. The aim of this study was to compare mortality rates and survival in a Dutch cohort of SDHD variant carriers with those in the general population. The study was conducted at the Leiden University Medical Center, a tertiary referral center for patients with paragangliomas. Included subjects all tested positive for SDHD variants before 1 July 2012 and visited the departments of Otorhinolaryngology or Endocrinology at least once or had a diagnosed paraganglioma and a SDHD variant-positive family history. Clinical data were retrieved from medical records, information on mortality was obtained from the Municipal Personal Records Database, and mortality rates for the Dutch population were obtained from the Dutch Central Bureau of Statistics, stratified by sex, age and date. SDHD variant carriers were followed from the date of first SDHD variant-related contact until death, emigration or 12 December 2012 and the standardized mortality ratio (SMR) was calculated. Two-hundred and seventy-five SDHD variant carriers were included in the study, of which 80% carried the c.274G>T, p.(Asp92Tyr) variant, had a mean duration of follow-up of 7.6 years, yielding 2242 person-years of observation for analysis. There were 18 deaths in the SDHD variant carrier group; two were paraganglioma related. The SMR for the whole cohort was 1.07 (95% confidence interval 0.67–1.73). In conclusion, mortality in SDHD variant carriers is not substantially increased. Additional studies are required to confirm these findings