Trends in incidence and 5‐year mortality in men with newly diagnosed, metastatic prostate cancer—A population‐based analysis of 2 national cohorts

Helgstrand, John Thomas; Røder, Martin Andreas; Klemann, Nina; Toft, Birgitte Grønkær; Lichtensztajn, Daphne Y.; Brooks, James D.; Brasso, Klaus; Vainer, Ben; Iversen, Peter

doi:10.1002/cncr.31384

Cited by 75 publications

(57 citation statements)

References 27 publications

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“…De novo metastatic disease represents 5-10% of prostate cancer (PCa) diagnoses but contributes to almost 50% of PCa related deaths [1,2]. The incidence of de novo metastatic diagnosis is rising, potentially related to improved imaging modalities and decreased prostate specific antigen (PSA) screening [3,4].…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer

et al. 2019

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Word count abstract: 293Word count text: 2592 This is the accepted manuscript of the article, which has been published in European Urology. 2019, 75(4), 667-675. http://dx. AbstractBackground: Several systemic therapeutic options exist for metastatic castratesensitive prostate cancer (mCSPC). Circulating tumour DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer (mCRPC) and can influence decision-making, but remains untested in mCSPC. Objective:To determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically-relevant information to a prostate biopsy. Design, Setting, and Participants:We collected plasma cell-free DNA (cfDNA) from 53 newly diagnosed patients with mCSPC and, where possible, during treatment.Targeted sequencing was performed on cfDNA and DNA from diagnostic prostate tissue. Results and Limitations:Median ctDNA fraction was 11% (range 0-84) among untreated patients but lower (1.0%, range 0-51) in patients after short term (median 22 days) androgen deprivation therapy (ADT). TP53 mutations and DNA repair defects were identified in 47% and 21% of the cohort, respectively. Concordance for mutation detection in matched samples was 80%. Combined ctDNA and tissue analysis identified potential driver alterations in 94% of patients, whereas ctDNA or prostate biopsy alone was insufficient in 19 cases (36%). Limitations include the use of a narrow gene panel and undersampling of primary disease by prostate biopsy.Conclusions: ctDNA provides additional information to a prostate biopsy in men with de novo mCSPC, but ADT rapidly reduces ctDNA availability. Primary tissue and ctDNA share relevant somatic alterations, suggesting that either are suitable for molecular subtyping in de novo mCSPC. The optimal approach for biomarker development should ! 3 utilize both a tissue and liquid biopsy at diagnosis, as neither captures clinically-relevant somatic alterations in all patients. Patient summary:In men with advanced prostate cancer, tumour DNA shed into the bloodstream can be measured by a blood test. The information from this test provides complementary information to a prostate needle biopsy and could be used to guide management strategies.! 4

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Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer

et al. 2019

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“…The PSA test was developed to detect metastatic recurrence in prostate cancer patients, but in the 1980s, the PSA test was rapidly adopted as a screening test without evidence that it reduced mortality from prostate cancer. This led to an explosion in the number of prostate cancers diagnosed each year, peaking in 1992 [8,9]. Ultimately, it was recognized that the PSA test identifi ed a reservoir of indolent prostate cancers whose early detection and treatment did not decrease mortality.…”

Section: Prostate Cancermentioning

confidence: 99%

“…Ultimately, it was recognized that the PSA test identifi ed a reservoir of indolent prostate cancers whose early detection and treatment did not decrease mortality. Prostate cancer screening guidelines have since been revised, and recommendations for PSA screening are much more limited to populations at increased risk [8,9]. This was one of the earliest examples of an "over diagnosis of cancer", in which screening detects nonlethal, early cancers.…”

Section: Prostate Cancermentioning

confidence: 99%

Cancer Prevention and Control: Then and Now

Ganz¹

2018

NAM Perspectives

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“…In this issue of Cancer , Helgstrand and colleagues present a unique assessment of the prostate cancer screening question. For more than 25 years, the medical profession, especially in the United States, has struggled with the issue.…”

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confidence: 99%

“…Helgstrand and colleagues present an ecological study comparing prostate cancer outcomes between similar populations from 2 different health care environments; the United States, where screening started 10 to 15 years earlier, and Denmark, where screening is less popular even today . The size of the populations are such that this is an effectiveness study.…”

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confidence: 99%