Prostate-only Radiotherapy Research Articles

External Beam Radiation Therapy (EBRT) and High-Dose-Rate (HDR) Brachytherapy for Intermediate and High-Risk Prostate Cancer: The Impact of EBRT Volume

Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site. A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive. Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed. A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.

Whole-Pelvic Versus Prostate-Only Radiation Therapy in Unfavorable Intermediate-Risk and High-Risk Prostate Cancer Treated with Androgen Deprivation Therapy and Brachytherapy Boost

The ASCENDE-RT randomized controlled trial showed that brachytherapy boost significantly reduces biochemical recurrence in unfavorable intermediate-risk and high-risk prostate cancer treated with whole-pelvic radiation therapy (WPRT) and androgen deprivation therapy (ADT). However, previous level 1 data have not shown an oncologic benefit for WPRT compared to prostate-only radiation therapy (PORT) in patients who did not receive brachytherapy boost. Therefore, we examined the association between WPRT, compared to PORT, and overall survival in patients with unfavorable intermediate-risk or high-risk prostate cancer treated with brachytherapy boost and ADT. Using the National Cancer Database, we identified 7,292 men diagnosed with unfavorable intermediate-risk disease (Gleason 4+3 or ≥2 intermediate-risk factors [Gleason 3+4, prostate-specific antigen (PSA) 10-20 ng/mL, or cT2b-T2c stage]) or high-risk disease (Gleason 8-10, PSA >20 ng/mL, or cT3-T4 stage) from 2004 through 2014 who were treated with brachytherapy boost, ADT, and either WPRT or PORT to 39.6-50.4 Gy. Patients with nodal or metastatic disease were excluded. Risk of lymph node metastases was estimated using the Roach formula ([2/3] × PSA + 10 × [Gleason score - 6]). Cox proportional hazards regression was used to examine the association between WPRT, versus PORT, and overall survival. Median follow-up was 6.3 years. The study cohort consisted of 35.1% unfavorable intermediate-risk patients and 64.9% high-risk patients. Overall, 52.5% of patients received WPRT. On multivariable analysis, WPRT, compared to PORT, was not associated with a significant improvement in overall survival for the entire cohort (adjusted hazard ratio [AHR] 1.02, 95% confidence interval [CI] 0.91-1.14, P =0.702). This lack of overall survival benefit was observed for subgroups of unfavorable intermediate-risk patients (AHR 1.12, 95% CI 0.93-1.35, P =0.246), high-risk patients (AHR 0.98, 95% CI 0.85-1.12, P =0.726), and patients with >15% risk of lymph node metastases (AHR 1.00, 95% CI 0.89-1.13, P =0.985). These results suggest that patients with unfavorable intermediate-risk or high-risk prostate cancer treated with brachytherapy boost and ADT may not benefit from receiving WPRT. Providers should thoughtfully weigh the risks and benefits of WPRT compared to PORT when planning to treat unfavorable-risk patients with brachytherapy boost and ADT.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial

The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. National Cancer Institute.

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: "low risk" (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus "high risk" (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46Gy). The total dose recommended to the prostate moved from 66Gy to 70Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. With a median follow-up of 11.4years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy.

Pelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy. Twenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose-volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. The incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

Whole-Pelvis Versus Prostate-Only Radiation Therapy and Androgen Deprivation Therapy: Effects on Mortality Risk

Whole-Pelvis Versus Prostate-Only Radiation Therapy and Androgen Deprivation Therapy: Effects on Mortality Risk

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) using Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.

Abstract 3438: Whole pelvis versus prostate-only radiotherapy with or without short course androgen deprivation therapy and mortality risk

Abstract Purpose: To determine whether extent of prostate radiotherapy (i.e. whole-pelvic radiotherapy (WPRT) versus prostate/seminal-vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). Methods: A multi-institutional cohort of 3,709 prostate cancer patients was prospectively assembled from 1991-2006. Median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration 4.2months). 70% of patients had unfavorable-risk disease (Gleason ≥7; PSA ≥10ng/mL; or stage ≥T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. A test for interaction between radiation volume and ADT use was conducted. Results: After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR] 0.58; 95% confidence interval [CI] 0.38-0.89; p = 0.01), or with ADT (AHR 0.71; 95%CI 0.58-0.90; p = 0.004). However, combining WPRT and ADT did not further improve ACM in comparison to either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the RT treatment volume and ADT (AHR 1.61; 95%CI 1.004-2.58; p = 0.048). Conclusions: Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, though combining the two does not yield greater benefit. This observation suggests a shared mechanism for this risk-reduction which we hypothesize to be sterilization of micrometastatic disease within the pelvic lymph nodes. Citation Format: Lior Z. Braunstein, Ming-Hui Chen, Daniel E. Dosoretz, Sharon Salenius, Michael Katin, Akash Nanda, Anthony V. D'Amico. Whole pelvis versus prostate-only radiotherapy with or without short course androgen deprivation therapy and mortality risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3438. doi:10.1158/1538-7445.AM2015-3438

Patient-reported gastrointestinal and genitourinary toxicity after prostate cancer treatment: A comparison between radiotherapy including pelvic nodes and prostate-only radiotherapy.

22 Background: To evaluate side effects of radiotherapy (RT) including the pelvic nodes in patients with prostate cancer. Methods: 143 patients with high risk prostate cancer (Pca) receiving whole pelvic radiotherapy (WPRT) was matched to a group of 142 patients receiving RT towards the prostate and seminal vesicles only (PORT). Both groups were given 78 Gy towards the prostate and 50 Gy towards the seminal vesicles. The WPRT group also received 50 Gy towards the pelvic nodes. WPRT was given with intensity modulated RT or volumetric modulated arc therapy technique and the group treated towards the prostate and seminal vesicles only was treated with 3-dimensional conformal RT. Gastrointestinal (GI) and genitourinary (GU) side effects were evaluated with patient-reported questionnaires and with the RTOG scale, scored by treating physician, at baseline and one-year after RT. Results: Overall the side effects were mild. At one-year follow up there were significant differences regarding morning urgency, mucus- and blood in stool between the two groups (Table 1). The WPRT group expressed lesser complications in all of these cases. In the RTOG GU and GI scores there were no differences between the groups. About 20% had RTOG grade 2 GU score and 2%/1% had RTOG grade 3 score in the PORT and WPRT groups, respectively. The numbers for RTOG grade 2 GI scores were 11% and 5% in the PORT and WPRT groups, respectively. None of the groups reported RTOG grade 3 GI symptoms. Conclusions: Whole pelvic RT can be done with a very satisfying profile of side effects. Sometimes even lesser gastrointestinal reported side effects are seen with the newer techniques compared to prostate only radiotherapy with older techniques. [Table: see text]

Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

IntroductionThe purpose of this study was to describe the pattern of nodal relapse with 18F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methodsEighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. ResultsFourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38–54.80], p=0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2–L3. Conclusion3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2–L3 safely to cover 95% of nodal stations at risk of an occult relapse.

Pattern of occult nodal relapse diagnosed with 18F fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy.

77 Background: 11C or 18F-labeled choline PET/CT has led to better understanding of the lymph drainage pattern of prostate cancer. It can provide radiation oncologists with maps to guide the delivery of prophylactic pelvic radiotherapy while minimizing radiation toxicity to non-target normal tissue with intensity modulated radiation therapy (IMRT). The purpose of this study was twofold: (1) to describe the pattern of nodal relapse in prostate cancer patients with biochemical failure after prostate-only radiotherapy; and (2) to determine whether patients with 18F-fluoro-choline (FCH) PET/CT positive nodes experienced treatment failure within the clinical target volume (CTV) defined by the RTOG guidelines (CTVRTOG). Methods: Between July 2008 and December 2012, 83 patients with a prostate cancer had a FCH PET/CT for biochemical failure after radiotherapy. Of 65 patients with FCH-positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy or radical prostatectomy followed by local radiotherapy. Each choline FCH positive node was assigned to a lymph node station and situated with regard to the CTVRTOG. Results: Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had two or more positive nodes on FCH PET/CT. Patients with FCH+ nodes outside the CTVRTOG were more likely than patients with FCH+ nodes inside the CTVRTOG to have two or more involved nodes (OR= 8.75, [95% CI: 1.38-54.80], p= 0.020). The ventral part of the external iliac station (29.0%) was the main site of relapse inside the CTVRTOG whereas relapses that occurred outside the CTVRTOGinvolved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. Conclusions: Nearly half of the patients had FCH+ nodes outside the CTVRTOG with a significantly higher number of nodes involved outside the CTVRTOG. Three-dimensional mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.

Radiation Therapy Oncology Group (RTOG) 9408: A Secondary Analysis of the Risk of Death From Second Cancers Comparing Whole Pelvic (WP) Radiation Therapy (RT) to Prostate Only (PO) RT and Neoadjuvant Hormonal Therapy (NHT) + RT to RT Alone

A post hoc analysis of the long-term results of RTOG 9413 suggested that the use of WP RT might be associated with an increased risk of death from second cancers (SCs), even though the incidence of SCs did not appear to be increased. There was also a trend for NHT to be associated with a lower risk of SCs compared to adjuvant hormonal therapy (AHT). This secondary analysis was performed to determine whether or not these findings could be confirmed by comparing patients (pts) treated with WP compared to PO RT with and without NHT on RTOG 9408.

Individualized image-based lymph node irradiation for prostate cancer

Controversy surrounds the benefit of whole pelvis radiotherapy (WPRT) over prostate-only radiotherapy (PORT) for intermediate-risk and high-risk patients with prostate cancer. In the PSA screening era, two large randomized trials as well as multiple retrospective studies comparing WPRT with PORT have been performed, albeit with contradictory results. Data regarding the use of WPRT in patients with biochemical recurrence after prostatectomy are scarce. As a consequence, the practice of WPRT varies worldwide. Advanced highly accurate imaging methods for the detection of lymph node metastases in patients with prostate cancer have been developed, such as PET, single photon emission computed tomography (SPECT), diffusion-weighted MRI and magnetic resonance lymphography (MRL). The use of these new imaging methods might improve nodal irradiation, as they can be used not only for selection of patients, but also for accurately determining the target volume to reduce geographical miss. Furthermore, these new techniques can enable dose escalation to involved lymph nodes.

Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score≥7 and/or prostate-specific antigen level≥20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p=NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p=.03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p=NS). Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.

Dosimetric predictors of diarrhea during radiotherapy for prostate cancer

To investigate dosimetric predictors of diarrhea during radiotherapy (RT) for prostate cancer. All patients who underwent external-beam radiotherapy as part of treatment for localized prostate cancer at the University of Texas Medical Branch, Galveston, TX, USA, from May 2002 to November 2006 were extracted from the own database. From the cumulative dose-volume histogram (DVH), the absolute volumes (V-value) of intestinal cavity (IC) receiving 15, 30, and 45 Gy were extracted for each patient. Acute gastrointestinal toxicity was prospectively scored at each weekly treatment visit according to CTC (Common Toxicity Criteria) v2.0. The endpoint was the development of peak grade >or= 2 diarrhea during RT. Various patient, tumor, and treatment characteristics were evaluated using logistic regression. 149 patients were included in the analysis, 112 (75.2%) treated with whole-pelvis intensity-modulated radiotherapy (WP-IMRT) and 37 (24.8%) with prostate-only RT, including or not including, the seminal vesicles (PORT +/- SV). 45 patients (30.2%) developed peak grade >or= 2 diarrhea during treatment. At univariate analysis, IC-V(15) and IC-V(30), but not IC-V(45), were correlated to the endpoint; at multivariate analysis, only IC-V(15) (p = 0.047) along with peak acute proctitis (p = 0.041) was independently correlated with the endpoint. These data provide a novel and prostate treatment-specific "upper limit" DVH for IC.

Whole Pelvic Radiotherapy Versus Prostate Only Radiotherapy in the Management of Locally Advanced or Aggressive Prostate Adenocarcinoma

To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity.

Significance of Whole-Pelvic Radiotherapy For High-Risk Prostate Cancer Patients After Radical Prostatectomy

Evaluation of: Spiotto MT, Hancock SL, King CR: Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients.Int. J. Radiat. Oncol. Biol. Phys.69, 54–61 (2007). Although most patients with localized prostate cancer are successfully treated with radical prostatectomy, high-risk patients often manifest biochemical and/or clinical relapse. Adjuvant or salvage radiotherapy is utilized for the treatment of these patients. For definitive radiotherapy for untreated prostate cancer, a randomized clinical study (radiation therapy oncology group [RTOG] 94–13), suggested superior effects of whole-pelvic radiotherapy to prostate-only radiotherapy. On the contrary, for adjuvant or salvage radiotherapy after radical prostatectomy, the role of whole-pelvic radiotherapy has not been extensively investigated. This retrospective study demonstrated better biochemical relapse-free survival in high-risk patients receiving adjuvant or salvage whole-pelvic radiotherapy, when combined with concurrent hormonal therapy, compared with prostate bed radiotherapy. Selection for good candidates for whole-pelvic radiotherapy after radical prostatectomy will be confirmed in future and a large-scale randomized clinical trial is required before the final conclusion can be made.

Whole-pelvis, “mini-pelvis,” or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial

The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether "mini-pelvis" (MP; defined as > or = 10 x 11 cm but < 11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms 1 and 2 of the study. Eligible patients had a risk of lymph node (LN) involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and another group of 324 patients were randomized to receive PO RT + N&CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an "MP" field and the smaller a PO field. The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.

Does Treatment of the Pelvic Nodes with IMRT Increase Late Rectal Toxicity over Conformal Prostate-Only Radiotherapy to 76 Gy?

To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate. 68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months). At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6%+/-4% for WP-IMRT/PB and 21.2%+/-6% for P-3D-CRT (p=0.06). The difference became significant (HR [hazard ratio]=0.1, 95% CI [confidence interval]: 0.0-0.6; p=0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity. Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.