Clinical Investigation
18F-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

https://doi.org/10.1016/j.ijrobp.2014.05.050Get rights and content

Purpose

To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy).

Methods and Materials

Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic 18F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale.

Results

Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%.

Conclusions

At early follow-up, 18F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.

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

References (27)

Cited by (23)

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  • 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]

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Conflict of interest: none.

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