HDR boost (real time) in patients with localized prostate cancer: technical description and preliminary results
Spira G¹, Weise C¹, Neubauer S², Blumberg J¹, Ernst C¹, Mühlnickel W¹, Derakhshani P²

Department of Radiation Oncology, Klinik am Ring, Cologne 1
Department of Urology, Klinik am Ring, Cologne 2

It has been well documented that the outcome of prostate cancer treatment depends on the dose administered. Hence, techniques have been developed that allow high-dose administration without increasing the complications, e.g. external radiotherapy combined with high-dose radiation (HDR) boost. In this study we analyse the technique and protocol of real-time HDR boost together with clinical results and quality of dosimetric parameters that support its use.

Between June 2003 and December 2007, 416 patients with prostate cancer were treated with 50.4 Gy of external irradiation to the pelvis (single fraction 1.8 Gy) and 3 HDR brachytherapy fractions (each 7.5Gy) at the end of a 5-week radiotherapy course. All brachytherapy implants were planned using the Nucletron SWIFT realtime ultrasound based planning system. The 1997 American Joint Commission on Cancer (AJCC) system was used to establish disease stage. Patients with low-risk (7.8%),  intermediate-risk (40.1%) and high-risk (52.1%) without metastases were eligible for the brachytherapy. 53% of Patients received neoadjuvant or adjuvant androgen deprivation therapy. Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel statement. Toxicity was scored according to RTOG guidelines.

The mean age of patients was 67.5 years (range 50.5-86). Median follow-up was 31 months (range: 12-56). Median PSA decreased from initially 11 ng/ml to 0.15 ng/ml after 36 months. No grade 4 complications were noted. Mean V100 prostate in all patients was 94.8% (range 74-99.8), mean D90 prostate was 7.97 Gy (range 5.3-9.8), median D10 urethra was 8.56 Gy (range 6.9-11.2) and median D10 rectum was 4.5 Gy (range 2.0-7.4). Patients were stratified for prostate volume. In the 76 patients with prostate volumes above 40 cc there was no major difference in dosimetric quality as compared to small prostates (D90 Prostate 7.96 vs. 7.97, V100 93.6 vs. 95.1, D10 Urethra 8.58 vs. 8.55, D10 Rectum 4.96 vs. 4.36).

The good results of biochemical control, few complications and excellent quality of dosimetric parameters suggest that external radiotherapy combined with HDR brachytherapy should be considered as first-choice in the treatment of localised prostate cancer of high- and intermediate-risk. Our study could prove that large prostates can be treated with equal dosimetric results as small glands.

Prospective study on quality-of-life and toxicity of high-dose-rate brachytherapy as an interstitial boost for localized prostate cancer

Derakhshani P^1,2, Neubauer S^1,2, Weise C^1,3, Spira G^1,3

(1) West German Prostate Center, Cologne, Germany
(2) Department of Urology, Klinik am Ring, Cologne
(3) Department of Radiooncology, Klinik am Ring, Cologne

Background and purpose:
We report on the outcome, toxicities and quality-of-life (QoL) of patients after high-dose-rate (HDR)-brachytherapy as a boost to external beam radiotherapy (EBR) for intermediate and high risk localized prostate cancer.
Materials and methods:
416 patients were treated in a single institution with HDR-brachytherapy in afterloading-technique as a boost to 3D-conformal EBR (50.4 Gy) between April 2003 and December 2006. Patients were classified as low-risk in 7.8%, intermediate-risk in 40.1% and high-risk in 52.1%. 53% of patients received neoadjuvant or adjuvant androgen deprivation therapy. Patients were followed in terms of PSA-levels, QoL, urinary function and sexual status. Validated questionnaires (IPSS; EORTC QLQ C30, PR25-Prostate-Module, IIEF5) were prospectively administered to all patients before and at 1, 3, 6, 12 and 24 months after treatment.
Results:
Median follow-up of patients was 34 months (12-56 months). Median PSA for intermediate-risk and high-risk groups decreased from initially 11 ng/ml to 0.15 ng/ml after 36 months. 3-year biochemical control rate for hormone naive patients, as defined by the ASTRO, was 87%. Urinary function (before HDR mean IPSS 8.9) worsened at 3, 6 and 12 months after HDR but remained stable (mean IPSS 10.6/9.3/10.3). Urinary bother score (UB) in PR25 was 30.17 immediately after HDR and improved significantly over the next twelve months (mean UB 23.61) to almost baseline 19.05 at 24 months. There was no change in bowel function (BF) throughout the study period (before HDR score 4.06, after HDR mean score 5.81). General health status (GHS) before HDR was excellent (score 72.41) and showed only slight decrease at all intervals after HDR (mean score 67.25). At 24 months patients reached baseline in GHS with a mean score of 69.84.
Conclusions:
Combined HDR-brachytherapy for intermediate and high-risk prostate cancer results in excellent biochemical control and quality of life with minor acute or late complications.

Prospective analysis of long-term health-related quality-of-life after permanent brachytherapy for prostate cancer

Derakhshani P^1,2, Spira G^1,3, Weise C^1,3, Neubauer S^1,2

(1) West German Prostate Center, Cologne, Germany
(2) Department of Urology, Klinik am Ring, Cologne
(3) Department of Radiooncology, Klinik am Ring, Cologne

Background and purpose:
Important criteria for patients seeking non-surgical treatment options for localized prostate cancer are expected influences on their quality of life. Aim of our study was to prospectively evaluate long-term urinary, bowel and sexual function status after permanent brachytherapy (PB) with I125-seeds using validated quality-of-life (QoL) questionnaires.
Materials and methods:
939 patients were treated in a single European institution with permanent seed implants between December 2000 and June 2006 using iodine stranded seeds. Out of those 506 consecutive patients (treated between July 2004 and June 2006) were separated and followed in terms of QoL, urinary function and sexual status. Validated questionnaires (IPSS, EORTC QLQ-C30, PR25-Prostate-Module, IIEF5) were administered to patients before and at 1, 3, 6, 12, 24, and 36 months after treatment.
Results:
Median follow-up of patients was 32.4 months (16 to 41 months). Urinary function (before PB mean IPSS 6.7) significantly worsened at 3 and 6 months after PB (mean IPSS 13.2/9.9) but returned to pre-treatment levels after 12 months (mean IPSS 8.2). Urinary bother score (UB) in PR25 was significantly worse at 3 and 6 months after PB and reached baseline at 12 months. 67.7% of patients had normal erectile function in IIEF5 before PB. In potent patients erectile dysfunction was noted at intervals 12, 24 and 36 months after PB in 35.3%, 31.8% and 33%. General health status (GHS) before PB was excellent (score 88.85) and remained stable at all intervals after PB (mean score 89.82). There was no change in bowel function (BF) throughout the study period (before PB score 3.06, after PB mean score 5.1).
Conclusions:
General health status of patients after permanent prostate implant is excellent throughout treatment period. The rate of long-term erectile dysfunction remains low. The results of our study show that permanent brachytherapy leads to only minor deterioration in quality of life and transient urinary symptoms.

Prospektive Analyse der langfristigen gesundheitsrelevanten Lebensqualität nach definitiver LDR-Brachytherapie der Prostata

Derakhshani P^1,2, Spira G^1,3, Weise C^1,3, Neubauer S^1,2

(1) Westdeutsches Prostatazentrum, Klinik am Ring, Köln
(2) Abteilung für Urologie, Klinik am Ring, Köln
(3) Abteilung für Radioonkologie, Klinik am Ring, Köln

EINLEITUNG:
Die Einflüsse auf die Lebensqualität (LQ) sind wichtige Kriterien vor der Therapieentscheidung für Patienten mit lokal begrenztem Prostatakarzinom. Ziel der Studie war es anhand von validierten Fragebögen langfristige Veränderungen von LQ, Miktion, Darmfunktion und Sexualfunktion nach permanenter LDR-Brachytherapie (PB) zu erfassen.
MATERIAL UND METHODEN:
Zwischen 12/00 und 06/06 wurden 939 Patienten mit einer PB (125-Jod-Seeds) behandelt. Aus diesem Kollektiv wurden 506 konsekutive Patienten (behandelt 12/04 bis 06/06) in Hinblick auf Lebensqualität, Miktions- und Sexualfunktion prospektiv untersucht. Validierte Fragebögen (IPSS, QLQ-C30, PR25-Modul, IIEF5) wurden vor und bis 36 Monate nach der Behandlung ausgefüllt.
ERGEBNISSE:
Der mediane Follow-Up der Patienten betrug 32 Monate (16-41). Die Miktion (vor PB IPSS 6,7) war 3 und 6 Monate nach PB deutlich verschlechtert (13,2/9,9), erreichte aber nach 12 Monaten das Ausgangsniveau (8,2). Die Miktionssymptomatik im PR25 zeigte 3 und 6 Monate nach PB eine signifikante Verschlechterung, lag aber nach 12 Monaten wieder auf Ausgangsniveau. 67,7% der Patienten hatten im IIEF5 eine normale erektile Funktion vor PB. Bei den potenten Patienten wurde eine erektile Dysfunktion 12, 24 und 36 Monate nach PB bei 35,3%, 31,8% und 33% festgestellt. Der allgemeine Gesundheitszustand vor PB war ausgezeichnet (88,85) und blieb nach PB durchgehend stabil (89,82). Es gab keine Veränderungen der Darmfunktion (vor PB 3,06, nach PB 5,1).
SCHLUSSFOLGERUNG:
Der allgemeine Gesundheitszustand und die Lebensqualität der Patienten nach einer PB bleiben insgesamt exzellent. Die Rate der erektilen Dysfunktion bleibt langfristig stabil. Unserer Studie zeigt, dass die PB nur zu einer vorübergehenden Verschlechterung der Miktionsfunktion führt.

Rezidivfreies Überleben und dosimetrische Ergebnisse von Patienten mit lokal begrenztem Prostatakarzinom nach interstitieller 125-Iod-LDR-Brachytherapie

Neubauer S^1,2, Derakhshani P^1,2, Weise C^1,3, Spira G^1,3

(1) Westdeutsches Prostatazentrum, Köln, Deutschland
(2) Abteilung für Urologie, Klinik am Ring, Köln
(3) Abteilung für Radioonkologie, Klinik am Ring, Köln

EINLEITUNG:
Wir berichten über die lokale Tumorkontrolle und korrelieren diese zu dosimetrischen Daten bei Patienten mit lokal begrenztem Prostatakarzinom nach 125-Iod LDR-Monotherapie mit einem Follow-Up von bis zu 7 Jahren.
MATERIAL UND METHODEN:
651 Patienten mit lokal begrenztem Prostatakarzinom erhielten zwischen Dezember 2000 und Dezember 2004 eine perineale Seedimplantation mit realtime-modifizierter Dosisplanung als Monotherapie. 501 (77%) Patienten hatten ein niedriges Risiko, 148 (23%) ein mittleres Risiko und 2 waren in der Hochrisikogruppe. 599 Patienten (92%) wiesen einen Gleason-Score 6 oder weniger auf, die Verteilung der klinischen Stadien war 2,4% T1a-b, 68,7% T1c, 27,8% T2a und 1,1% T2b.
ERGEBNISSE:
Die mediane Nachbeobachtungszeit war 52,7 Monate (Range: 35.3-84.0). Das 5-Jahres-PSA-rezidivfreie Überleben (PRFS) für Patienten mit niedrigem und mittleren Risiko betrug 97,5% und 94%. Es wurden eine mediane V100-Prostata von 98% und eine mediane D90-Prostata von 177 Gy erreicht. Die D90-Prostata war >130/140/150/160 Gy in 98,2/93,9/90,4 und 85,6% der Patienten. Die mediane D30-Urethra betrug 199,3 Gy und die mediane D10-Rektum 88,2 Gy.
Patienten mit PSA-Rezidiv hatten eine mediane D90-Prostata von 167,8 Gy, bei Patienten ohne Rezidiv betrug sie 175,9 Gy. Die Patienten wurden nach PSA-Nadir <0,5 oder >0,5 ng/ml stratifiziert (98,2% und 87,6%). Eine Subanalyse der Gruppe mit niedrigem Risiko zeigte ein 5-Jahres PRFS für PSA-Nadir <0,5 oder >0,5 ng/ml von 98% und 92%.
SCHLUSSFOLGERUNG:
Unsere Untersuchung zeigte eine Korrelation der Ergebnisse nach LDR-Brachytherapie mit PSA-Wert, Tumor Stadium, Gleason-Score und dosimetrischer Qualität. In unserer Serie war die D90-Prostata, als Merkmal der Qualität einer Implantation, der stärkste prognostische Faktor.