International Journal of Radiation Oncology*Biology*Physics
Clinical Investigation18F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients
Introduction
Radical prostatectomy (RP) is the most widely used treatment for localized prostate cancer. After prostatectomy, a prostate-specific antigen (PSA) increase >0.2 ng/mL is generally shared as a biochemical recurrence: this event occurs in 15%-50% of radically operated patients within 10 years 1, 2. Unfortunately, it remains uncertain whether a PSA increase after RP indicates a local, regional, or distant recurrence (3). In addition, according to data from the Southwest Oncology Group 8794 trial (4), salvage radiation therapy (SRT) to prostatic fossa is generally shared as the standard of care for patients with rising PSA after RP.
Even if prostatic fossa is the standard target volume, the optimal SRT dose is unknown. The American Society for Radiation Oncology consensus guidelines, published in 1999, recommend that “the highest dose of radiation therapy that can be given without morbidity is justifiable” (5). In effect, the latest guidelines of the European Association of Urology (6) recommend a total dose up to 64-66 Gy with standard fractionation at a PSA serum level ≤0.5 ng/mL. However, Stephenson et al (7) analyzed 1540 patients who underwent SRT with PSA <0.5 ng/mL at time of recurrence and recorded a 6-year progression-free survival rate of 48%. Moreover, a recent trial (8) in which patients with a PSA level >0.2 ng/mL at time of recurrence were treated with 66-Gy SRT recorded a biochemical no evidence of disease rate at 2 years of 69%.
Therefore, to improve SRT results, treatment should be undertaken as early as possible (ie, when PSA value is ≤0.2 ng/mL); otherwise a dose >60-66 Gy should be administered.
King and Kapp (9) suggested that the dose-response relationships for salvage and radical radiation therapy are similar. Bernard et al (10) confirmed this dose-response relationship for SRT, with lower rates of biochemical failure in patients treated with total dose >66.6 Gy. Subsequently, some authors proposed to increase the total radiation dose up to 70 Gy or more. However, radiobiological models (11) suggested severe late gastrointestinal (GI) and genitourinary (GU) toxicity rates if increasing SRT dose. Thus, to improve the therapeutic ratio of SRT, higher doses could be administered to smaller volumes. Currently the identification of recurrence by means of new imaging modalities might allow more precise radiation therapy, with dose escalation for evident disease only.
In such settings, 18F-choline positron emission tomography/computed tomography (PET/CT) should be able to detect the site of recurrence and modify clinical target volume (CTV) delineation accordingly (12).
From January 2009, all patients referred to our institution with biochemical recurrence after RP were admitted to dynamic 18F-choline PET/CT; high-dose SRT was delivered accordingly. Here we retrospectively review data of a cohort, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose SRT (78-80 Gy) delivered according to the functional data.
Section snippets
Patient population
Between January 2009 and September 2011, 60 consecutive patients with rising PSA after RP were treated at our institution. Recurrence was defined as a PSA value >0.2 ng/mL (13) or with re-rising PSA above detection limits (mostly 0.05 ng/mL) confirmed by another PSA increase in a consecutive measurement (7).
All patients underwent dynamic 18F-choline PET/CT at time of biochemical recurrence, and CTVs have been defined accordingly. Patients with distant disease or negative scan results at PET/CT
Results
Sixty patients with biochemical recurrence after RP were treated. Their characteristics are summarized in Table 1.
Forty-three patients (71.7%) had a Gleason score of ≥7 at time of surgery; 16 (26.7%) had a positive surgical margin and 14 (23.3%) had seminal vesicle involvement at pathologic specimens. Median (range) time from RP to SRT was 46.6 (9.4-182.7) months, with a median PSA value before SRT of 0.9 (0.2-11.7) ng/mL. A PSA value of <0.5 ng/mL at time of SRT was recorded in 18 patients
Discussion
Our study of 60 patients with biochemical recurrence after RP confirmed the possibility of delivering a functional imaging-guided treatment with boost to up to 80 Gy. In these patients, 18F-choline PET/CT recorded a local recurrence, with 5 patients also recording nodal disease. Increasing total dose up to 80 Gy in this area did not translate into higher toxicity: GI grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 GU toxicity. Moreover, only 1
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Cited by (23)
PET/Computed Tomography for Radiation Therapy Planning of Prostate Cancer
2017, PET ClinicsCitation Excerpt :In a study of 93 patients with sites of recurrence in lymph nodes, patients had a better biochemical recurrence-free survival if they had been treated with salvage lymph node dissection combined with radiotherapy than if they had been treated with only salvage lymph node dissection.38 In 1 study, 4 of 11 (36%) patients underwent a change of treatment decisions after a PET/CT.24 In a second study, choline F 18 PET/CT detected a site of recurrence in the prostate bed.39 The detected site of recurrence was treated with a boost up to 80 Gy.
New Clinical Indications for <sup>18</sup>F/<sup>11</sup>C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature [Figure presented]
2016, European UrologyCitation Excerpt :After a careful analysis of the abstracts and the recovery of all full-texts, additional references were identified (Fig. 1). Table 1 reports the characteristics of selected studies [5–70]. Nine articles were related to the role of PET/CT with radiolabelled choline for the initial staging of PCa (n = 650 patients), 22 to the evaluation of recurrence of PCa (n = 4315 patients), seven to salvage lymphadenectomy (n = 394 patients), nine to radiotherapy (RT) planning (n = 434 patients), six related to the assessment of therapeutic agents (n = 195 patients; ie, androgen deprivation therapy [ADT], enzalutamide or abiraterone acetate), five to PET/MRI (n = 156 patients), and finally six and two to new radiopharmaceutical agents, such as 68Ga-PSMA (n = 907 patients) and 18F-FACBC (n = 71 patients), respectively.
Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using <sup>11</sup>C-choline PET/CT
2016, Revista Espanola de Medicina Nuclear e Imagen MolecularA cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective
2016, Critical Reviews in Oncology/HematologyCitation Excerpt :Moreover, the heterogeneity test of the three randomized trials recorded equivocal effects of baseline factors on bPFS (Table 1), and thus fails to support one single factor as a driver for ART. Furthermore, the inclusion of early salvage RT at very low PSA levels (King, 2013), or the adoption of high dose RT (D’Angelillo et al., 2014), seems logical evenif not formally assessed in a RCT. Three ongoing randomized trials (TROG RAVES 0803, GETUG-17 and RADICALS) should clarify the benefit of ART or SRT and their applicability with androgen deprivation therapy (ADT).
PET/computed tomography in the individualization of treatment of prostate cancer
2015, PET ClinicsCitation Excerpt :However, the investigators observed an early biochemical partial response in 70% of cases, and treatment was well tolerated, with grade 3 acute toxicity in the genitourinary tract observed only in 2.4% of the population. D’Angelillo and colleagues35 investigated a cohort of 60 patients with BR after RP, treated according to 18F-choline PET/CT, to evaluate toxicity and feasibility of high-dose (80 Gy) S-RT. All patients were treated on prostate bed, whereas 20% of patients were treated with additional nodal irradiation.
Conflict of interest: none.