Intensity-Modulated Radiotherapy (IMRT) of Localized Prostate Cancer

PURPOSE: The present status of intensity-modulated radiation therapy (IMRT) for treatment of localized prostate cancer is discussed. METHODS: The technological basis of IMRT and the rationale for the use in treatment of prostate cancer are described. Clinical results from the literature are presented and treatment strategies for further reduction of safety margins are outlined. RESULTS AND DISCUSSION: Multiple planning studies demonstrated the dosimetric advantage of IMRT compared to three-dimensional conformal radiotherapy. Though randomized studies are missing, retrospective studies indicate that improved dose distributions of IMRT transfer into improved rates of local control and/or lower rates of rectal toxicity. However, with standard safety margins the benefit of IMRT seems to be limited. Image guidance is considered to be essential to reduce errors of patient setup and internal motion of the prostate.     

3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

PURPOSE: Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. PATIENTS AND METHODS: Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) < or = 10 ng/ml, Gleason score < or = 7 and clinical stage < or = T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT((R)) was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D(ref)) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D(90), D(10) urethra, and D(10) rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales. RESULTS: Median D(90) was 106% of D(ref) (range: 93-115%), median D(10) urethra 159% of D(ref) (range: 127-192%), and median D(10) rectum 55% of D(ref) (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. CONCLUSION: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.     

Long-Term Results in Three-Dimensional Conformal Radiotherapy of Localized Prostate Cancer at Moderate Dose (66 Gy)

PURPOSE: Biochemical control (bNED), disease-specific survival (DSS), overall survival (OS), and late gastrointestinal (GI) and urogenital (UG) side effects (EORTC/RTOG) of patients with long-term follow-up were evaluated. PATIENTS AND METHODS: Three-dimensional radiotherapy up to 66 Gy with/without additional hormonal therapy was performed in 154 prostate cancer (T1-3 N0 M0) patients. According to T-stage, pretreatment prostate-specific antigen (PSA) and grading, patients were divided into a low-, intermediate-, and high-risk group. The 5-, 8-, and 10-year actuarial rates of bNED, DSS and OS and late side effects were calculated. RESULTS: Median follow-up was 80 months. Additional hormonal therapy was given in 57% of patients. Distribution concerning risk groups (low, intermediate, high) showed 15%, 49%, and 36% of patients, respectively. bNED 5-, 8-, and 10-year actuarial rates were 46%, 44%, and 44%. DSS 5-, 8- and 10-year rates amounted to 96%, 90%, and 82%. OS 5-, 8- and 10-year rates were 81%, 64%, and 56%. In uni- and multivariate analysis, only pretreatment PSA (<10 vs. >or=10 ng/ml; p<0.05) and PSA nadir (<0.5 vs. >or=0.5 ng/ml; p<0.0001) affected bNED significantly. Age, risk group, T-stage, grading, and hormonal therapy had no significant influence on bNED, DSS, and OS. Rates of late GI and UG side effects grade>or=2 at 5 years were 17% and 15%. CONCLUSION: Current dose escalation studies with better bNED rates may be able to further increase long-term clinical outcome.     

Experiences with a New High-Dose-Rate Brachytherapy (HDR-BT) Boost Technique for T3b Prostate Cancer

PURPOSE: Experiences with a new high-dose-rate brachytherapy (HDR-BT) boost technique in 41 patients with stage T3b prostate cancer are presented. PATIENTS AND METHODS: The patients received 18 Gy of HDR-BT (9 Gy on days 1 + 8) plus 50.4 Gy of EBRT. 20 patients (group A) had BT applicators placed into the prostate alone resulting in 18 Gy to prostate and 0 Gy (tip) to 12 Gy (base) to seminal vesicles (SV). The cumulative EQD2 (equivalent dose in 2-Gy fractions, alpha/beta 1.5 Gy) to the SV was 47.5-73.3 Gy. 21 patients (group B) had BT applicators placed into both prostate and SV resulting in 18 Gy to prostate and to > 80% (but not 100%) of the SV (cumulative EQD2 81.5-101.5 Gy). Both groups were compared for acute and late toxicity and for biochemical relapse-free survival (bRFS). RESULTS: The 3-year bRFS was 57% for group A and 79% for group B patients (p = 0.29). A grade 3 acute toxicity (CTC 2.0) was not observed. Grade 2 acute toxicity (proctitis, cystitis, skin toxicity) was comparable in both groups. A grade 3 late toxicity did not occur. Impotence rates were 35% in group A and 24% in group B, respectively (p = 0.73). CONCLUSION: The new HDR-BT technique (group B) was associated only with minor acute and late toxicity and appears to result in better bRFS than the conventional HDR-BT technique (group A). The results must be confirmed in a prospective trial.     

Dose Escalated External Beam Radiotherapy versus Neoadjuvant Androgen Deprivation Therapy and Conventional Dose External Beam Radiotherapy for Clinically Localized Prostate Cancer: Do we Need Both?

Strahlentherapie und Onkologie - Several randomized trials have demonstrated that men with localized prostate cancer benefit from the use of short-term neoadjuvant androgen deprivation therapy...     

The Utility of Diffusion-Weighted Imaging and Perfusion Magnetic Resonance Imaging Parameters for Detecting Clinically Significant Prostate Cancer

IntroductionTo establish the diagnostic performance of the parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging at 3T in discriminating between non-clinically significant prostate cancers (ncsPCa, Gleason score [GS] < 7) and clinically significant prostate cancers (csPCa, GS ≥ 7) in the peripheral zone.Materials and MethodsTwenty-six male patients with peripheral zone prostate cancer (PCa) who had undergone 3T multiparametric magnetic resonance imaging (MRI) scan prior to biopsy were included in the study and evaluated retrospectively. The GS was obtained by both standard 12-core transrectal ultrasound guided biopsy and targeted MRI-US fusion biopsy and then confirmed by prostatectomy, if available. For each confirmed tumour focus, DCE-derived quantitative perfusion metrics (Ktrans, Kep, Ve, initial area under the curve [AUC]), the apparent diffusion coefficient (ADC) value, and normalized versions of quantitative metrics were measured and correlated with the GS.ResultsKtrans had the highest diagnostic accuracy value of 82% among the DCE-MRI parameters (AUC 0.90), and ADC had the strongest diagnostic accuracy value of 87% among the overall parameters (AUC 0.92). The combination of ADC and Ktrans have higher diagnostic performance with the area under the receiver operating characteristic curve being 0.98 (sensitivity 0.94; specificity 0.89; accuracy 0.92) compared to the individual evaluation of each parameter alone.The GS showed strong negative correlations with ADC (r = −0.72) and normalized ADC (r = −0.69) as well as a significant positive correlation with Ktrans (r = 0.69).ConclusionThe combination of Ktrans and ADC and their normalized versions may help differentiate between ncsPCa from csPCa in the peripheral zone.     

Radiotherapy of Prostate Cancer with Multileaf Collimators (MLCs)

Background and Purpose: A technical modification for radiotherapy of prostate cancer is presented to smooth the scalloped dose pattern that occurs at treatment field edge, when a multileaf collimator (MLC) has been used. Material and Methods: Ten patients with prostate cancer receiving postoperative, adjuvant irradiation were studied prospectively. By a three-dimensional planning system (TMS, Helax 6.1B) the irradiation was planned for an 18-MV linear accelerator (Primus 1, Siemens). The volumes of interest (VOI) were the planning target volume (PTV; the region of the prostate including the seminal vesicles), the volume of rectum (V_rectum) and urinary bladder (V_bladder). Two four-field techniques (0°, 90°, 180°, 270°) were planned using beams eye view for setting the leaf position of the MLC. For technique A the MLC was adapted to the PTV using a 0° collimator angle for the lateral fields. For technique B the collimator angle of the lateral fields was optimized to compensate the cascade field shape. Dose-volume histograms of PTV, V_rectum and V_bladder were analyzed. The dose was prescribed for the reference point according to ICRU 50. Film dosimetry was used to show the dose pattern at the field edge produced by the two techniques. Results: Dose to PTV did not differ between technique A and B. Median dose to V_rectum was 82.6% for technique A and 77.3% for technique B (p < 0.001). Technique A irradiates a larger V_rectum than technique B being significant for all isodose levels tested. Median dose to V_bladder did not differ for technique A and B (p > 0.05). Conclusion: The presented technical modification is an effective method to blur the staggered dose distribution that results, when the MLC is conventionally stepped to adapt to the dorsal, irregular PTV border in irradiation of prostate. Especially for irradiation to escalated dose levels, this modification may reduce the dose to the rectum and thus the rectal side effects in comparison to the conventional MLC fields.