Salvage re-irradiation using stereotactic body radiation therapy for locally recurrent prostate cancer: the impact of castration sensitivity on treatment outcomes

Abstract

Background Advances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage. Methods A prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6–8) Gray (Gy). Results Median follow-up was 28 months. Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients (p = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients (p < 0.001), and 3-year metastasis-free survival was 90% versus 27% (p < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity. Conclusions Early delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.

Serum Paraoxonase-1 Activity and the Risk of Prostate Cancer Recurrence in Patients Treated with Radiotherapy

“…PCa cells, however, may develop resistance to radiation. This highly unpredictable mechanism renders the treatment less effective and frequently causes recurrence after radical RT—up to one-third of PCa patients experience biochemical failure after RT [ 2 ]. Despite identifying several molecular mechanisms associated with radioresistance, the ability to predict an individual PCa patient’s response to RT is still limited and based mostly on the pretreatment assessment of prostate specific antigen (PSA), tumor stage and Gleason score [ 3 , 4 ].…”

Reirradiation of Locally Recurrent Prostate Cancer with Cyberknife® System or Volumetric Modulated Arc Therapy (VMAT) and IGRT-Clarity®: Outcomes, Toxicities and Dosimetric Evaluation

“…In total, 10 studies reported data regarding retreatment with CK [9,10,[16][17][18][19][22][23][24]30,31], 3 with VMAT [21,26,29], 1 with CK or BT [20], 1 IMRT/VMAT [25], 1 Tomotherapy [15], 1 CK or VMAT [28], and 1 IMRT or CK [27]. The first radiation treatment was delivered with only EBRT in 10 studies [9,15,18,19,24,26,28,30,31] as exclusive or adjuvant treatment, 9 studies reported data on treatment with EBRT and/or BT [10,17,[20][21][22][23]25,27,29], only 1 study reported 1 treatment performed with SBRT [19], 1 study reported treatment with EBRT including 3DCRT, IMRT, and PT [16].…”

“…Reirradiation prescription doses ranged from 15-18 Gy/3 fx [15,21] to 38 Gy/6 fx [25]. ADT was given with reirradiation in 132 patients (29%), collecting the 16 studies reporting this finding [10,[16][17][18][19][20][21][22][23][24][25][26][27][29][30][31].…”

“…In terms of efficacy, the rates of BRFS (Biochemical Relapse Free Survival) and DMFS (Distant Relapse Free Survival) were analyzed at 2 years by 12 studies [9,10,[16][17][18]21,22,[25][26][27][28][29]31], (Table 7). Toxicities were assessed by the CTCAE version 3.0 scale [10,16], or 4 [9,[18][19][20]22,[24][25][26]28,29,31], or by the RTOG/EORTC scale [17,21,23,25,27,28,30].…”

“…Regarding late genitourinary toxicity: grade 3 was observed in 8 studies [10,[16][17][18]23,26,27,29] with a median percentage of 3% (1.5-12.5%); grade 2 in 12 studies [10,[16][17][18]20,21,23,25,[27][28][29]31] with median percentage of 9% (3-30%).…”