Shorter treatment may provide better outcome for some prostate cancer

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Treatment with a shorter course of radiation, using higher doses per treatment over fewer days, may be the preferred approach in appropriately selected patients with localised prostate cancer, found a US meta-analysis.

Prostate cancer is the most common cancer among males in the US. Approximately, 180,000 men are diagnosed each year, and approximately 95% of these men have localised disease that is potentially curable. Previously, studies have consistently demonstrated that conventionally fractionated high dose external beam radiation therapy (CRT), consisting of daily treatment for two months, decreases prostate cancer recurrence, and improves metastasis-free survival.

Previous studies also demonstrate that moderate hypo-fractionated radiation therapy (HRT), consisting of daily treatment for one month using a larger dose per treatment, provides a similar low risk of recurrence, and may even be lower with HRT than CRT.

To accurately test the hypothesis of a lower risk of recurrence with HRT, a study led by investigators at Brigham and Women’s Hospital performed a systematic review and meta-analysis, pooling available data, to assess whether an improved risk of recurrence could be demonstrated using HRT compared with CRT, in addition to assessing the relative impact of these two treatments on bladder and rectal function.

Researchers found that the one-month duration HRT, was associated with a significant improvement in recurrence compared to the two-month duration CRT and therefore would be reasonable to consider in men with intermediate risk prostate cancer and who do not have risk factors that could predispose the patient to bladder side effects several years after the treatment is complete.

“Our results provide evidence for clinicians to consider HRT as compared with CRT as a preferred radiation treatment in men with intermediate-risk prostate cancer and at low risk of other complications,” stated Dr Trevor Royce, radiation oncologist at Brigham and Women’s Hospital and first author of the study. “Treatment with a shorter course of radiation and higher doses over fewer days may be the preferred approach in appropriately selected patients with localised prostate cancer, reducing treatment time and cost to the patient, and increasing patient convenience and access to treatment.”

Researchers analysed data from over 5,000 men from three randomised studies comparing HRT with CRT in men with prostate cancer. Of the 5,484 men, 3,553 men, or 64.8% had intermediate-risk prostate cancer. HRT as compared with CRT was associated with a significant 13% reduction in the risk of recurrence. No significant difference in overall survival was found between HRT and CRT but researchers noted that the possibility exists that men in excellent health could also achieve an overall survival benefit with HRT as compared with CRT.

“Late bladder and urethra toxicities were noted to be higher in the HRT as compared to CRT group which necessitates carefully choosing men who are not at risk for sustaining a late bladder or urethral side effect,” said Dr Anthony D’Amico, chief, genitourinary radiation oncology at Brigham and Women’s Hospital, and senior author of the study. “Men to exclude would be those who get up more than three times at night to urinate, or have urgency to urinate, or incontinence, or men who are on anti-coagulants that could increase the risk of bleeding,” D’Amico said.

Researchers say further study is needed using individual patient-level data among men with high risk prostate cancer to assess the benefit of HRT and whether treatment toxicity, particularly those to the bladder and urinary system are also low with HRT.

Abstract
Context: Whether hypofractionated radiation therapy (RT) compared with conventionally fractionated RT provides comparable or possibly improved cancer control without increased toxicity in localized prostate cancer (PC) remains unknown.
Objective: Realizing from the CHHiP trial that outcomes are highly sensitive to the dose fractionation schedule and number of treatments, we conducted a systematic review and meta-analysis selecting only the randomized noninferiority trials, because the randomized arms closely approximated one another in terms of the dose fractionation schedule, and compared cancer control and toxicity of hypofractionated RT with conventionally fractionated RT for localized PC.
Evidence acquisition: Randomized noninferiority trials evaluating hypofractionated (2.4–4 Gy daily fractions for 15–30 treatments) versus conventionally fractionated RT (1.8–2 Gy daily fractions for 40–45 treatments) in men with localized PC were selected. Studies that were not noninferiority trials, used extreme hypofractionation, or treated metastatic disease were excluded. Three studies were retained for analysis. Data were pooled using a random-effects model to determine hazard ratio (HR) and risk ratio (RR). Heterogeneity was assessed via chi-square test, I2 statistics, and metaregression. The primary outcome was disease-free survival (DFS), defined as death from any cause or biochemical, local, regional, or distant progression.
Evidence synthesis: Of the 5484 men, 3553 (64.8%) had intermediate-risk PC. Hypofractionated RT as compared with conventionally fractionated RT was associated with significantly improved DFS (HR 0.869; 95% confidence interval [CI], 0.757, 0.998; p = 0.047), whereas overall survival was not (HR 0.84; 95% CI, 0.66, 1.07; p = 0.16). Acute grade 2 or higher gastrointestinal toxicity was significantly increased with hypofractionation (RR 1.42; 95% CI 1.15, 1.77; p = 0.002); however, this did not translate into late grade 2 or higher gastrointestinal toxicity. An increase in late grade 2 or higher genitourinary complications was observed (RR 1.18; 95% CI 0.98, 1.43; p = 0.08).
Conclusions: Hypofractionated RT as compared with conventionally fractionated RT could improve DFS in men with intermediate-risk PC and, therefore, would be reasonable to consider in men who do not have risk factors for late genitourinary complications.
Patient summary: Treatment with a shorter course of radiation, using higher doses per treatment over fewer days, may be the preferred approach in appropriately selected patients with localized prostate cancer.

Authors
Trevor Joseph Royce, Dong Hoon Lee, NaNa Keum, Nitipong Permpalung, Calvin J Chiew, Sherise Epstein, Kristen M Pluchino, Anthony V D’Amico

Brigham and Women’s Hospital material
European Urology Focus abstract


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