Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials

Tran, Eric; Paquette, M.; Pickles, Tom; Jay, Justin; Hamm, Jeremy; Liu, Mitchell; Lim, Jan; Keyes, Mira; Kwan, Winkle; Tyldesley, Scott

doi:10.1016/j.radonc.2013.05.003

Cited by 12 publications

(7 citation statements)

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“…In the UK there has been a shift in treatment patterns away from ADT alone towards ADT + EBRT. The evidence suggests that this change in practice will substantially prolong survival (as was observed in British Columbia due to the move away from EBRT with short-term ADT to EBRT with long-term ADT from the late 1990s [17] ). However, between 7% and 26% of men with locally advanced prostate cancer were still being treated with ADT alone, which has been shown to be inferior to ADT + EBRT.…”

Section: Discussionmentioning

confidence: 95%

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer

South

Parulekar

Sydes

et al. 2016

European Urology Focus

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BackgroundRecent trials have shown that the addition of external beam radiotherapy (EBRT) to androgen deprivation therapy (ADT) improves survival among men with locally advanced prostate cancer.ObjectiveTo examine the potential impact of these trials on changes in clinical practice and life-years saved.Design, setting, and participantsA model was developed to examine the impact of changes in clinical practice in the UK. A survey of clinicians who treat men with prostate cancer in the UK and Canada was performed.MeasurementsOutcomes of interest were the proportion of patients treated with different approaches and the predicted number of life-years saved due to changes in clinical practice. Survey data were cross-tabulated and Pearson's χ2 tests were applied.Results and limitationsThe survey was completed by 193 clinicians (105 from the UK, 80 from Canada), of whom 70% were clinical/radiation oncologists, 8% were medical oncologists, and 15% were urologists. UK respondents were more likely to report a change in practice in response to the results (44% UK vs 21% Canada). Canadians were more likely to have already been using ADT plus radiotherapy (77% Canada vs 56% UK). The increase in the proportion of patients in the UK treated with ADT + EBRT could result in around 3730–5177 extra life-years at 15 yr from a cohort of 7930 men diagnosed in a single calendar year, compared to if all had been treated with ADT alone.ConclusionsTrial findings have changed clinical practice, meaning that men with locally advanced prostate cancer are likely to survive longer.Patient summaryDoctors in the UK have changed practice in response to evidence on the superiority of hormone therapy plus radiotherapy to hormone therapy alone. These changes will improve the survival of men with locally advanced prostate cancer. Further reductions in the use of hormone therapy alone could further improve survival.

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Section: Discussionmentioning

confidence: 95%

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer

South

Parulekar

Sydes

et al. 2016

European Urology Focus

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“…Active surveillance (AS) is an alternative to initial radical treatment of lowrisk PCa, even if the current parameters used for selection and follow up, such as clinical T stage, total PSA, PSA density, Gleason score (GS), and number of positive prostate biopsy cores, incorrectly exclude some patients eligible for AS and misclassify some who actually harbor significant disease [5]. Currently, the available preoperative tools used in this clinical setting, such as PSA, digital rectal examination, and biopsy results fail to accurately predict PCa aggressiveness and distinguish between insignificant PCa and clinically significant PCa and underestimates the GS compared to prostatectomy specimens in up to 66% of patients, based on PSA levels, biopsy GS, and clinical stage [6].…”

Section: Introductionmentioning

confidence: 99%

“…Besides these variables, which have been incorporated in a validated predictive model to predict Gleason upgrading [7], a number of biomolecular markers have been associated with Gleason upgrading [4,6]. Recently numerous preoperative prognostic tools analyzed the ability of prostate cancer antigen 3 (PCA3), sarcosine, [-2]proP-SA, and Prostate Health Index in predicting the pathological features at radical prostatectomy (RP) [8,9].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil, Platelets, and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk Prostate Cancer Patients

et al. 2018

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Background: Several biochemical and clinical markers have been proposed for selecting patients for active surveillance (AS). However, some of these are expensive and not easily accessible. Moreover, currently about 30% of patients on AS harbor aggressive disease. Hence, there is an urgent need for other tools to accurately identify patients with low-risk prostate cancer (PCa). Patients: We retrospectively reviewed the medical records of 260 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/mL, 2 or fewer cores involved with cancer, Gleason score (GS) ≤6 grade, and prostate-specific antigen density < 0.2 ng/mL/cc. Methods: Univariate and multivariate analyses were performed to evaluate the association of patient and tumor characteristics with reclassification, defined as upstaged (pathological stage >pT2) and upgraded (GS ≥7) disease. A base model (age, prostate-specific antigen, prostate volume, and clinical stage) was compared with models considering neutrophil to lymphocyte ratio (NLR) or platelets to lymphocyte ratio (PLR), monocyte to lymphocyte (MLR), and eosinophil to lymphocyte ratio (ELR). OR and 95% CI were calculated. Finally, a decision curve analysis was performed. Results: Univariate and multivariate analyses showed that NLR, PLR, and ELR upgrading were significantly associated with upgrading (ORs ranging from 2.13 to 4.13), but not with upstaging except for MLR in multivariate analysis, showing a protective effect. Conclusion: Our results showed that NLR, PLR, and ELR are predictors of Gleason upgrading. Therefore, these inexpensive and easily available tests might be useful in the assessment of low-risk PCa, when considering patients for AS.

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“…The highly heterogeneous prognosis of localized disease poses a great challenge for clinicians and investigators, since prognostic assessment is essential to assess the balance of benefits and harms of treatment [2][3][4][5]. While a subset of patients can be safely actively monitored avoiding sexual, urinary and bowel toxicity associated with local treatments [2], patients with aggressive disease require a multimodality approach that includes surgery [3] and/or radiation therapy plus adjuvant hormonal treatment [4]. The clinical stage, prostate-specific antigen (PSA) levels and the biopsy Gleason score have been incorporated in an extensively employed risk classification model originally …”

mentioning

confidence: 99%

“…In a cohort of 993 men with Gleason 6 or 3 + 4 prostate cancer who were enrolled in an active surveillance protocol, 267 patients received radical treatment and biopsy grade progression was the cause of intervention in 94 (35%) of patients [2]. Furthermore, in patients undergoing radiotherapy, biopsy Gleason score is essential for optimal dosing and duration of androgen deprivation treatment [4]. Finally, patients with clinical T2 disease but pathologic T3 disease who undergo radical prostatectomy also have to receive subsequent radiotherapy in addition to surgery, with increased morbidity and decreased quality of life [3].…”

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confidence: 99%

Urotensin II Receptor on Preoperative Biopsy is Associated with Upstaging and Upgrading in Prostate Cancer

et al. 2015

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Aim: A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients. Methods: A retrospective review of formalinfixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry. Results: A total of 58 subjects undergoing radical prostatectomy were included. At multivariate analysis, low UTII-R expression was a significant predictor of Gleason upgrading, with an odds ratio of 10.3 (95% CI: 1.55-68.4), and of pathology upstaging, with an odds ratio of 11.1 (95% CI: 1.23-100.48). Conclusions: UTII-R expression on biopsy was associated with Gleason upgrading and pathology upstaging in prostate cancer patients. KEYWORDS• Gleason score • prostate cancer • urotensin II receptor Prostate cancer is the most prevalent malignant tumor in men, with varying incidences among different geographical areas and populations because of a complex interplay of genetic and socioeconomic factors [1]. The highly heterogeneous prognosis of localized disease poses a great challenge for clinicians and investigators, since prognostic assessment is essential to assess the balance of benefits and harms of treatment [2][3][4][5]. While a subset of patients can be safely actively monitored avoiding sexual, urinary and bowel toxicity associated with local treatments [2], patients with aggressive disease require a multimodality approach that includes surgery [3] and/or radiation therapy plus adjuvant hormonal treatment [4]. The clinical stage, prostate-specific antigen (PSA) levels and the biopsy Gleason score have been incorporated in an extensively employed risk classification model originally 3092RESEaRch aRticlE Ferro, Buonerba, Terracciano et al. future science group developed by D'Amico et^al. [5]. The biopsy Gleason score has also been included in models predicting organ-confined disease [6] as well as lymph node involvement [7], and it is associated with outcome even in patients with advanced disease receiving systemic treatment [8,9].Preoperative staging underestimates pathologic stage and prostate biopsies underestimate the Gleason score compared with prostatectomy specimens in up to 66% of patients, depending on PSA levels, biopsy Gleason score and clinical stage [10]. Apart from these variables, which have been incorporated in a validated predictive model to predict Gleason upgrading [11], a number of biomolecular markers were associated with Gleason upgrading [12,13]. Upgrading and upstaging have important therapeutic implications, as biopsy Gleason score and clinical stage along with PSA levels are the mainstay of the treatment-decision algorithm for localized prostate cancer [2][3][4][5]. Notably, baseline radiographic clinical staging has serious limitations.Urotensin II (UTII) is a vasoconstrictive agent that binds to UTII receptor (UTII-R) and is able to stimulate human corticoadrenal carcinoma proliferation [14]. In thr...

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Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials

Cited by 12 publications

References 19 publications

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer

Neutrophil, Platelets, and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk Prostate Cancer Patients

Urotensin II Receptor on Preoperative Biopsy is Associated with Upstaging and Upgrading in Prostate Cancer

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