A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis

Abstract

Purpose Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of 18F-DCFPyL PET/CT Restaging

“…RFS (nadir PSA þ 2) was 48% after median follow-up of 31 months and was lower compared with other salvage radiotherapy series. 14,16 Differences in RFS may be secondary to differences in patient population, brachytherapy volumes, dosimetry, and fractionation.…”

Studies of Intra-Fraction Prostate Motion During Stereotactic Irradiation in First Irradiation and Re-Irradiation

“…SBRT salvage therapy has been evaluated mainly retrospectively ( 8 ) and several prospective multicenter studies are ongoing ( 11 , 12 , 37 )…”

“…Traditional treatment options for the local treatment of intra-prostatic recurrence include radical prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound (HIFU) ( 2 ). Re-irradiation using SBRT has emerged as an important technique for this indication showing, with a short follow-up of 26 months, a good local control rate of 83.2% (95% CI, 75.5% – 90.9%), a survival without biological recurrence of 59.3% (95% CI, 47.9% – 70.7%) with a low severe toxicity rate Grade ≥2 for gastrointestinal (GI) 1.1% (95% CI, 0.1% – 2.0%), and genitourinary (GU) 10.5% (95% CI, 5.5% –15.4%) ( 8 – 12 ).…”

Salvage Reirradiation Options for Locally Recurrent Prostate Cancer: A Systematic Review

“…Based on the available data, grade 3 or higher GU and GI toxicity with SBRT was rare, although follow-up beyond 2 years is limited (9,(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). SBRT has the potential to limit the risk of severe late GU/GI toxicity compared with less conformal EBRT techniques (69). Careful patient selection remains vital, especially for those at greater risk of excess toxicity following salvage therapy.…”

“…The median number (range) of included patients for individual BT and SBRT studies was 44 ) and 42 (23-100) respectively. The median age (range) at salvage treatment was 70 years (59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76) for BT studies and 74 years (64-78) for SBRT studies. The median PSA at primary treatment for the BT and SBRT studies were 10.9 ng/mL (range 7.4-26.4) and 10.3 ng/ mL (range 8.7-13.0) respectively.…”