Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Nabid, Abdenour; Carrier, Nathalie; Vigneault, Éric; Nguyen, Thu Van; Vavassis, Peter; Brassard, Marc-André; Bahoric, Boris; Archambault, Robert; Vincent, François; Bettahar, R.; Wilke, Derek; Souhami, Luís

doi:10.1016/j.ejca.2020.10.023

Cited by 34 publications

(27 citation statements)

References 25 publications

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“…All other series included patients treated in the 1990s and/or included patients treated with conventional fractionation RT, brachytherapy alone, or brachytherapy boosts. [2][3][4][7][8][9][15][16][17] Table 3 compares our series to similar prospective and retrospective studies. Although our analysis did not show statistical significance, the trend supports the well-known benefit of ADT in regards to biochemical control, as well as the improved tumor control associated with modern treatment techniques and image guidance (7-y BCRFS of 86% for IR patients treated with RT alone).…”

Section: Discussionmentioning

confidence: 84%

“…The randomized controlled trials that demonstrated improved outcomes with ADT utilized outdated radiation delivery techniques and delivered lower doses of radiation than are used today 2–4. More recent studies evaluating the addition of short-term ADT to dose-escalated radiation have demonstrated biochemical and disease-specific recurrence reductions, with no impact on OS 7–9. In addition, many investigators have raised the possibility of potential cardiotoxicity and mortality with gonadotropin-releasing hormone (GnRH) agonists.…”

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confidence: 99%

“…[2][3][4] More recent studies evaluating the addition of short-term ADT to dose-escalated radiation have demonstrated biochemical and disease-specific recurrence reductions, with no impact on OS. [7][8][9] In addition, many investigators have raised the possibility of potential cardiotoxicity and mortality with gonadotropin-releasing hormone (GnRH) agonists. Although the exact relationship has yet to be elucidated, in 2010, this prompted the American Heart Association (AHA) to issue a warning on risk of cardiotoxicity associated with ADT.…”

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confidence: 99%

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Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Post¹,

Kahn²,

Turina³

et al. 2022

American Journal of Clinical Oncology

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Objectives: In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. Materials and Methods: Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. Results: Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. Conclusions: In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

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Section: Discussionmentioning

confidence: 84%

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confidence: 99%

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confidence: 99%

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Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Post¹,

Kahn²,

Turina³

et al. 2022

American Journal of Clinical Oncology

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“…There is a temptation to analyze clinical outcomes from these trials, particularly with the omission of ADT in patients with unfavorable intermediate-risk prostate cancer who benefit from the addition of ADT. 7,8 These trials had neither the primary objective nor power to evaluate clinical efficacy. However, Greco et al notably reported prostatespecific antigen relapses in 2 patients in the SBRT arm and 3 patients in the single dose radiation therapy arm at a median of 26.6 and 27.3 months, respectively, rendering 48-month actuarial biochemical recurrence−free survival of 85.7% versus 77.1%.…”

Section: Tumor Controlmentioning

confidence: 99%

Prostate SBRT Dose Escalation (9 Gy × 5, 13.3 Gy × 3, 24 Gy × 1): Are We Making Progress?

Nagar

Spratt

2021

International Journal of Radiation Oncology*Biology*Physics

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“… 3 – 5 Other randomized trials have demonstrated a modest survival advantage from the addition of short-term androgen deprivation therapy (ADT) to standard-dose EBRT compared with standard-dose EBRT alone. 6 , 7 …”

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Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

Lowenstein

Corrigan

et al. 2022

MDM Policy & Practice

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Background. For men with intermediate-risk prostate cancer (IRPC), adding short-term androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) has shown efficacy, but men are often reluctant to accept it because of its impact on quality of life. Methods. We conducted time tradeoffs (score of 1 = perfect health and 0 = death) and probability tradeoffs with patients aged 51 to 78 y who had received EBRT for IRPC within the past 2 y. Of 40 patients, 20 had received 6 mo of ADT and 20 had declined. Utility assessments explored 4 ADT-related side effects: hot flashes, fatigue, loss of libido/erectile dysfunction, and weight gain. Results. The most commonly reported “worst” treatment-related complication of ADT was fatigue (50% in both cohorts) followed by reduced libido/erectile dysfunction (40% in both cohorts). The utilities for fatigue were mean = 0.71 and median = 0.92 and for reduced libido/erectile dysfunction were mean = 0.81 and median = 0.92. Utilities did not differ significantly between cohorts. Assuming a 6-mo course of ADT, men reported being willing to trade 3 mo of life expectancy to avoid fatigue due to ADT and 1.8 mo to avoid sexual side effects. Patients in the ADT cohort were willing to accept the side effects of ADT in exchange for a mean 8% absolute increase in survival, whereas patients in the no ADT cohort required a 16% increase ( P < 0.001). Conclusions. When considering treatment with ADT, men with IRPC identified fatigue and sexual dysfunction as the most bothersome side effects. Patients who declined ADT expected a larger survival benefit than those who opted for treatment. Both groups expected a survival benefit exceeding that shown by recent trials, suggesting some men may be selecting treatments inconsistent with their preferences. Highlights This study demonstrates that prostate cancer patients receiving radiation therapy are reluctant to receive androgen deprivation therapy (ADT) most commonly due to anticipated fatigue and loss of libido/erectile dysfunction. Men who had received ADT reported they would require an average 8% absolute increase in survival to tolerate its side effects, whereas those who declined ADT would require an average 16% increase. Required thresholds are well above the estimated absolute survival benefit for ADT demonstrated in recent clinical trials, suggesting an unmet need for improved patient education regarding the risks and benefits of ADT.

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Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Cited by 34 publications

References 25 publications

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Prostate SBRT Dose Escalation (9 Gy × 5, 13.3 Gy × 3, 24 Gy × 1): Are We Making Progress?

Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

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Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Cited by 34 publications

References 25 publications

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer

Prostate SBRT Dose Escalation (9 Gy × 5, 13.3 Gy × 3, 24 Gy × 1): Are We Making Progress?

Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

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Prostate SBRT Dose Escalation (9 Gy × 5, 13.3 Gy × 3, 24 Gy × 1): Are We Making Progress?