Radiotherapy and Oncology 110 (2014) 240–244

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Prostate radiotherapy

Suggestion for the prostatic fossa clinical target volume in adjuvant or salvage radiotherapy after a radical prostatectomy Jun Su Park a, Won Park a,⇑, Hong Ryull Pyo a, Byung Kwan Park b, Sung Yoon Park b, Han Yong Choi c, Hyun Moo Lee c, Seong Soo Jeon c, Seong Il Seo c, Byong Chang Jeong c, Hwang Gyun Jeon c a Department of Radiation Oncology; b Department of Radiology; and c Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

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Article history: Received 17 July 2013 Received in revised form 2 January 2014 Accepted 2 January 2014 Available online 28 January 2014 Keywords: Prostate cancer Radiation therapy Clinical target volume Prostatectomy

a b s t r a c t Background and purpose: To assess the location of recurrent tumors and suggest the optimal target volume in adjuvant or salvage radiotherapy (RT) after a radical prostatectomy (RP). Material and methods: From January 2000 to December 2012, 113 patients had been diagnosed with suspected recurrent prostate cancer by MRI scan and received salvage RT in the Samsung Medical Center. This study assessed the location of the suspected tumor recurrences and used the inferior border of the pubic symphysis as a point of reference. Results: There were 118 suspect tumor recurrences. The most common site of recurrence was the anastomotic site (78.8%), followed by the bladder neck (15.3%) and retrovesical area (5.9%). In the cranial direction, 106 (87.3%) lesions were located within 30 mm of the reference point. In the caudal direction, 12 lesions (10.2%) were located below the reference point. In the transverse plane, 112 lesions (94.9%) were located within 10 mm of the midline. Conclusions: A MRI scan acquired before salvage RT is useful for the localization of recurrent tumors and the delineation of the target volume. We suggest the optimal target volume in adjuvant or salvage RT after RP, which includes 97% of suspected tumor recurrences. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 240–244

In Europe, prostate cancer is the most common male cancer, accounting for 22.8% of all new male cancer in 2012, and the incidence has been increased over the past two decades [1,2]. Radical prostatectomy (RP) is one of the standard treatments for clinically localized prostate cancer, and many studies have indicated that RP could increase the rate of long-term disease-specific survival. Recent reports have indicated that the 15-year prostate cancer-specific death rates after RP were 12–18% [3–5]. Some patients experience a biochemical or clinical recurrence after RP. Biochemical failure without clinical evidence of disease recurrence has been reported in 20–30% of patients after RP [6]. Recently, randomized trials reported that adjuvant radiotherapy (RT) reduced biochemical failure and disease recurrence, and also improved biochemical failure-free survival and overall survival, when compared with observations of pathologically high-risk patients [7–9]. Biochemical failure precedes distant metastasis and cancer-specific death. Studies from the Johns Hopkins University reported that the median time to metastasis after biochemical ⇑ Corresponding author. Address: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, 135-710 Seoul, Republic of Korea. E-mail address: [email protected] (W. Park). 0167-8140/$ - see front matter Ó 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.radonc.2014.01.001

failure was eight years, and that the median survival time after biochemical failure was 13 years [10]. The European Association of Urology (EAU) guideline recommends salvage RT for biochemical failure after RP [11]. Several single-institutional studies reported that the 5-year biochemical failure-free survival rate after salvage RT was 40–66% [12–14]. In addition, a multi-institutional, retrospective study reported similar results, which determined that the 4- and 7-year biochemical failure-free survival rates after salvage RT were 45% and 32%, respectively [15,16]. Intensity-modulated radiation therapy (IMRT) with imageguidance to reduce morbidity in the adjacent normal tissue is universally applicable in adjuvant or salvage RT. However, the most important issue is delineating the optimal target volume for adjuvant or salvage RT. Although several guidelines have been published for adjuvant RT target volume delineation [17–20], the optimal target volume for adjuvant or salvage RT remains controversial. In this study, we reviewed magnetic resonance imaging (MRI) scans that were acquired before salvage RT and assessed the location of suspected tumor recurrence to suggest the optimal target volume for adjuvant or salvage RT after RP.

J.S. Park et al. / Radiotherapy and Oncology 110 (2014) 240–244

Methods and materials Patient population From January 2000 to December 2012, 282 patients received salvage RT. From the total patient population, 113 patients fulfilled the following inclusion criteria: (1) RP as the primary treatment for prostate cancer, (2) no history of transurethral resection of the prostate or high-intensity focused ultrasound, (3) a PSA level that decreased below 0.2 ng/ml after RP, (4) a PSA level that rises again 0.2 ng/ml or above during follow up, and (5) diagnosis of a suspected tumor recurrence by MRI scan acquired before a salvage RT. Table 1 shows the characteristics of the 113 patients who were included in this study. Pathologic confirmation by transrectal ultrasonography-guided biopsy was performed in 8 patients. A total of 14 patients underwent hormone therapy before or during salvage RT. The median time interval between the RP and salvage RT was 27 months (range, 4–125 months). The median PSA nadir value after RP was 0.04 ng/ml (range, 0.01–0.19 ng/ml), and the median PSA value before salvage treatment was 0.43 ng/ml (range, 0.20–5.78 ng/ml). Seventy-nine patients received three-dimensional (3D) conformal RT that used 15 MV photons. The median total dose was 70.0 Gy (66.0–78.0 Gy), and a daily dose of 2.0 Gy was used. IMRT became available after November 2008, and 34 patients from this study received IMRT that used 10 or 15 MV photons. The median total dose was 68.6 Gy (67.2–70.0 Gy), and a hypo-fractionated daily dose of 2.4 or 2.5 Gy was used. For all patients, the clinical target volume (CTV) consisted of the prostate bed including suspected recurrent lesions and the rectal balloon was inflated during RT. The addition of whole pelvic irradiation was determined on an individual treatment basis.

MRI techniques and image analysis A MRI scan of the prostate was performed with either the 1.5 T (Signa, GE Medical Systems, Milwaukee, WI, USA) or 3.0 T systems (Intera Achieva 3T, Philips Medical System, Best, Netherlands) using a six-channel phased-array coil. Prior to the scan, 20 mg of butyl scopolamine (Buscopan, Boehringer, Ingelheim, Germany) was intramuscularly injected to suppress bowel peristalsis. Both T2-weighted images (T2WIs) and dynamic contrast-enhanced images (DCEIs) were included in all of the MRI scans. The T2WIs were acquired in the three orthogonal planes (axial, sagittal, and coronal). The following T2WI scan parameters were used for this study: repetition time (TR)/echo time (TE) ms, 2600–4200 ms/80–100 ms; slice thickness, 3 mm; interslice gap, 0.3–0.1 mm; matrix, 512  304; field of view (FOV), 15–20 cm; number of signals acquired, 3; and sensitivity encoding (SENSE) factor, 2. The DCEIs were collected using a 3D fast field echo

Table 1 Patients’ characteristics. Age (years) Initial PSA (ng/ml) Gleason score 66 7 P8 Tumor stage T2 T3a T3b Resection margin status Negative Positive PSA at failure (ng/ml)

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sequence with the following parameters: TR/TE, 7.4/3.9; flip angle, 25°; matrix, 224  179; slice thickness, 5 mm; interslice gap, none; FOV, 20 cm; and 11 partitions on a 3D slab. The 3D volume with 11 partitions was acquired every 5 s and a total of 58 scans were repeated. The dynamic acquisition consisted of one pre-contrast series and 57 subsequent post-contrast series. A post-contrast series was performed immediately after a bolus injection of gadopentetate dimeglumine (Magnevist, Schering, Germany), at a rate of 2 ml/s with a dose of 0.1 mmol per kilogram of body weight using a power injector. All of the images were archived with a Picture Archiving and Communication System (PACS; PathSpeed Workstation; GE Medical Systems, Milwaukee, WI, USA) and were interpreted by two experienced genitourinary radiologists. The presence of local recurrence was determined when the following two criteria were satisfied: (1) a focal lesion of iso to slightly high signal intensity on T2WIs and (2) an early enhanced focal lesion on DCEIs. The prostate MRI scans were performed within 3 weeks prior to the salvage RT. Localization of recurrent prostate cancer To represent the 3D coordinates of the recurrent prostate cancer, a reference point was established at the inferior border of the pubic symphysis (Fig. 1). The inferior border of pubic symphysis was easy to identify on computed tomography or MRI, thus it has reproducibility and little interobserver variation. The coordinates between the reference point and the center of the suspected tumor recurrence on the MRI scan were acquired using PACS. Statistical analysis The statistical significance between the recurrent sites and pathological stage was assessed with the Fisher’s exact test. A P-value of