title: SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer.
abstract: OBJECTIVE
  To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP).
  
  
  METHODS
  Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables.
  
  
  RESULTS
  Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them.
  
  
  CONCLUSIONS
  Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: aukishan@gmail.com.
authors: Amar U
authors: AU
authors: Kishan
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Pin-Chieh
authors: PC
authors: Wang
authors: Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California.
authors: Shrinivasa K
authors: SK
authors: Upadhyaya
authors: Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg, Germany.
authors: Henrik
authors: H
authors: Hauswald
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: D Jeffrey
authors: DJ
authors: Demanes
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Radiation Oncology, Stanford University, Stanford, California.
authors: Nicholas G
authors: NG
authors: Nickols
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Mitchell
authors: M
authors: Kamrava
authors: Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California.
authors: Ahmad
authors: A
authors: Sadeghi
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Patrick A
authors: PA
authors: Kupelian
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Michael L
authors: ML
authors: Steinberg
authors: Department of Radiation Oncology, Stanford University, Stanford, California.
authors: Nicolas D
authors: ND
authors: Prionas
authors: Department of Radiation Oncology, Stanford University, Stanford, California.
authors: Mark K
authors: MK
authors: Buyyounouski
authors: Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Christopher R
authors: CR
authors: King
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*
chemical_list: D017430:Prostate-Specific Antigen