Early radiation response between GnRH agonist versus antagonist combined with radiotherapy in high-risk prostate cancer.

97 Background: Degarelix, a GnRH antagonist, provides a very rapid and sustained testosterone suppression alongside with the VEGF pathway inhibition through the FSH receptors. This raises the question as to whether high risk localized prostate cancer (HRPCa) could respond differently to radiotherapy (RT) + Degarelix when compared with RT + GnRH agonist. Methods: 30 HRPCa patients were treated with exclusive RT combined with a GnRH agonist (n= 19) or Degarelix (n= 11). MRSI was performed before the start of hormones and 3 months after the end of RT. Choline (tumor metabolism) and citrate (healthy prostate metabolism) were quantified with MR spectroscopy and the slopes of gadolinium wash-in (SWI) and wash-out (SWO) were assessed in the peripheral zone (PZ), the central gland (CG) and the tumor with DCE-MRI. Results: At baseline, 14 patients had a T3 (46.7%) and 9 patients (30%) had a GS≥8. The median PSA values were 12.7 ng/mL [3.0-153.7] for agonists and 14.0 ng/mL [6.8-23.6] for Degarelix (p=ns). The mean prostate volumes (Pvol) were 32.0±15.5 mL for agonist and 33.0±10.0 mL for Degarelix (p=ns). The median dose of RT was 78Gy in each group, [72.0-80.0] with agonist and [70.2-80.0] with Degarelix. There were no significant differences in choline, citrate, SWI and SWO in the PZ, the CG and the tumor. At 3 months, Pvol were 20.8±8.0 mL for agonist and 21.4±6.2 mL for Degarelix (p=0.71) and the mean and median PSA values for agonist vs Degarelix were 0.5±0.8 ng/mL vs 0.1±0.1 ng/mL and 0.1 ng/mL [0.02-2.8] vs 0.1 ng/mL [0.005-0.3], respectively. Citrate was significantly decreased with Degarelix in the PZ (4.3±4.4 vs 1.1±0.8, p=0.0142), in the CG (4.0±4.0 vs 1.1±1.0, p=0.009) but not in the tumor (2.5±2.6 vs 1.7±1.9, p=0.23). Choline concentrations were similar between both groups in the PZ, the CG and the tumor. There was a trend towards a lower contrast uptake in the tumor with Degarelix (mean SWI and SWO: 134.6±56.2 s-1 vs 104.1±36.3 s-1, p=0.13 and 259.6±103.1 s-1 vs 306.1±70.4 s-1, p=0.15). Conclusions: Degarelix combined with RT offers a significant early, more profound metabolic atrophy in the prostate, but not in the tumor. There is a trend towards a lower tumor vascularization with Degarelix compared with GnRH agonists.

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Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.781121 ◽

2022 ◽

Vol 11 ◽

Author(s):

Ingrid Masson ◽

Martine Bellanger ◽

Geneviève Perrocheau ◽

Marc-André Mahé ◽

David Azria ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Propensity Score Analysis ◽

Volumetric Modulated Arc Therapy ◽

Late Toxicity ◽

Clinical Effectiveness ◽

High Risk Prostate Cancer ◽

Gu Toxicity ◽

Risk Prostate Cancer ◽

The Mean

BackgroundIntensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.Material and MethodsWe used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.ResultsThe mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.ConclusionUse of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

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Early results of localised, high-risk prostate cancer treated by moderate hypo-fractionation (70 Gy at 2·5 Gy per fraction): 5-year experiences of a moderate hypo-fractionation regimen

Journal of Radiotherapy in Practice ◽

10.1017/s1460396919000694 ◽

2019 ◽

Vol 19 (3) ◽

pp. 233-236

Author(s):

Ekkasit Tharavichitkul ◽

Somvilai Chakrabandhu ◽

Pitchayaponne Klunklin ◽

Wimrak Onchan ◽

Bongkot Jia-Mahasap ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Organs At Risk ◽

Intensity Modulated Radiation Therapy ◽

Standard Regimen ◽

High Risk Prostate Cancer ◽

Early Results ◽

Risk Prostate Cancer ◽

The Mean ◽

Fractionation Regimen

AbstractBackground:Radiotherapy is one of the treatments used to treat prostate cancer, and dose escalation to 74–78 Gy in conventional fractionation is the standard regimen. Currently, according to the hypothesis of low alpha/beta ratio in prostate cancer cells, using hypo-fractionation has been reported in many publications with promising results. This retrospective study was designed to evaluate the implementation of a moderate hypo-fractionation regimen in high-risk prostate cancer in our division.Materials and Methods:Between 2012 and 2017, 40 patients with high-risk, localised prostate cancer were treated by a moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) with intensity-modulated radiation therapy. The data related to treatment outcomes and toxicities were evaluated.Results:The mean PSA at diagnosis was 86·2 ng/mL (95% CI 49·9–122·4). Thirty-eight patients received long-term hormonal therapy. Fifty-two percent had a Gleason score of 8–10, and 65% had an initial PSA >20 ng/mL. The mean doses (in EQD2) to the D50% of PTV, D2% of organs at risk (bladder, rectum and bowels) were 80, 78·3, 76·4, and 50·2 Gy, respectively. Two patients had biochemical recurrence during the follow-up period.Conclusion:A moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) is feasible. Our experience found that this regimen yields tolerable, acceptable toxicity profiles in high-risk, localised prostate cancer patients.

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A prospective study evaluating oral-only hormonal therapy with radiation for intermediate or high-risk prostate cancer in men age ≥ 70 years or with moderate comorbidity.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.303 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 303-303

Author(s):

Benjamin Ernst Onderdonk ◽

Paige L. Dorn ◽

Fauzia Arif ◽

Daniel William Golden ◽

Theodore Karrison ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Gnrh Agonist ◽

Standard Of Care ◽

High Risk Prostate Cancer ◽

Biologic Effects ◽

Risk Prostate Cancer ◽

Related Quality ◽

Health Related ◽

A Prospective Study

303 Background: Androgen deprivation therapy (ADT) improves disease control in intermediate (IR) and high risk (HR) prostate cancer (PCa) treated with radiation therapy (RT), but also causes toxicity which may be worse in men of older age or with comorbidity. We hypothesized that dual agent ADT, replacing GnRH agonist for an oral 5-alpha-reductase inhibitor (5AR), would improve hormonal health-related quality of life (HRQOL) without compromising PCa outcomes. Methods: Patients with localized IR or HR PCa, age > 70 years and/or with Charlson comorbidity index (CCI) score > 2 were treated with bicalutamide and finasteride or dutasteride (oADT). A synchronous standard of care (SOC) cohort received bicalutamide and GnRH agonist. Median RT dose was 78 Gy. Dual agent ADT was given for 4 months (mo), while 5AR or GnRH agonist continued for an additional 2 years. The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26) hormonal HRQOL global score at 6 mo, with success defined as < 30% decline, requiring 40 men in the oADT group. Secondary endpoints included a log-rank comparison of freedom from biochemical failure (FFBF), and overall survival (OS). Results: Between 1/2011 and 8/2018, 40 and 30 men were prospectively enrolled in the oADT and SOC cohorts, respectively, with similar CCI scores > 2 (73% vs 66%, p=0.58), and age (mean 71, p=0.99). Median follow-up was 36 mo. Global scores for hormonal HRQOL at baseline, 6 mo, and 2 yr were 89, 88, 84 for the oADT group, and 92, 81, 83 for the SOC group; the declines from baseline to 6 mo (p=0.04) and 2 yr (p=0.05) were smaller in the oADT group. Sexual HRQOL was better preserved at 6 mo (p<0.01) in the oADT group, which maintained higher testosterone at 2 years (452 vs 44, p<0.01). There were no differences in urinary or bowel HRQOL. The 3-year FFBF was 90% vs 96% (p=0.83) and OS was 83 vs 86% (p=0.77) between the oADT and SOC groups, respectively. Conclusions: oADT improves hormonal and sexual HRQOL compared to SOC ADT in men age ≥ 70 or moderate comorbidity treated with RT. These groups could be further evaluated in a randomized comparison; post-ADT RNA expression to evaluate the relative biologic effects will be performed. Clinical trial information: NCT01342367.

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