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Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients.

ABSTRACT: Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.

SUBMITTER: Cailleteau A

PROVIDER: S-EPMC8739777 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients.

Cailleteau Axel A Sargos Paul P Saad Fred F Latorzeff Igor I Supiot Stéphane S

Frontiers in oncology 20211224

Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment ma ...[more]

PMID: 35004302

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Project description:BackgroundAdjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome.MethodsWe evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42-85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4-128.0 months).ResultsEarly SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14-0.75, p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02-1.44, p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02-1.79, p = 0.15).ConclusionFor patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients' postoperative clinical condition.Study registrationThe present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.

Project description:Cancer in the elderly remains an evolving issue and a health challenge. Several improvements in the radiotherapy field allow the delivery of higher doses/fractions with a safe toxicity profile, permitting the reduction of radiation treatment protocols in the elderly. Regarding breast, prostate, and lung cancer, the under-representation of older patients in clinical trials limits the extension of treatment recommendations to elderly patients in routine clinical practice. Among the feasible alternatives to standard whole breast radiotherapy (WBRT) in older patients are shorter courses using higher hypofractionation (HF) and accelerated partial breast irradiation (APBI). The boost continues to be used in women at high risk of local recurrence but is less widely accepted for women at lower risk and patients over 70 years of age. Regarding prostate cancer, there are no published studies with a focus on the elderly. Current management decisions are based on life expectancy and geriatric assessment. Regimens of HF and ultra-HF protocols are feasible strategies for older patients. Several prospective non-randomized studies have documented the safe delivery of ultra-HF for patients with localized prostate cancer, and multiple phase III trials and meta-analyses have confirmed that the HF regimen should be offered with similar acute toxicity regardless of patient age and comorbidity. A recent pooled analysis from two randomized trials comparing surgery to stereotactic body radiation therapy (SBRT) in older adult patients with early stage non-small cell lung cancer did show comparable outcomes between surgery and SBRT. Elderly cancer patients are significantly under-represented in all clinical trials. Thus, the inclusion of older patients in clinical studies should be strongly encouraged to strengthen the evidence base for this age group. We suggest that the creation of oncogeriatric coordination units may promote individualized care protocols, avoid overtreatment with aggressive and unrecommended therapies, and support de-escalating treatment in elderly cancer patients.

Project description:ContextRadiotherapy (RT) is a valid adjuvant treatment for men with high-risk pathological features after radical prostatectomy and a salvage treatment for biochemical recurrence. A major inconvenience is that RT takes course over 7-8 wk in these settings, which has been shown to limit its use. Retrospective and pilot prospective investigations suggest that hypofractionation may provide noninferior outcomes but report variable results regarding toxicities. Additionally, our evolving understanding of prostate cancer radiobiology suggests that hypofractionated regimens may not increase toxicity.ObjectiveWe examine and review the rationale and clinical evidence of hypofractionated RT in the adjuvant and salvage settings for prostate cancer.Evidence acquisitionWe reviewed relevant literature, with a particular focus on recent studies employing hypofractionated RT.Evidence synthesisHypofractionated RT in the adjuvant or salvage setting is not a standard option for prostate cancer RT outside of an investigational trial. While smaller studies show conflicting data regarding toxicity, initial evidence from larger clinical trials appears to demonstrate that hypofractionated postoperative RT is as effective and safe as conventionally fractionated courses.ConclusionsWith the growing acceptance of hypofractionation across other cancer sites and the rise of extreme hypofractionation for definitive prostate cancer treatment, hypofractionated postoperative therapy for prostate cancer is poised to become an option, as it may reduce the burden on men and treatment centers while maintaining clinical efficacy and safety. Prospective trials are currently ongoing to address efficacy and safety concerns.Patient summaryPostoperative radiotherapy is a potentially curative treatment for patients with high-risk disease or recurrence after surgery. Shortening of the treatment regimen with the availability of modern treatment delivery techniques in conjunction with the integration of molecular imaging information to refine treatment volumes may improve therapeutic benefit without increasing toxicity.

Dataset Information

Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients.

Publications

Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients.

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