Elective Pelvic Nodal Irradiation Research Articles

Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT

PurposeThe role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. MethodsThis retrospective study included patients who underwent 18F-DCFPyL PET/CT with a PSA > 0.1 ng/mL after either radical prostatectomy (RP) or RP and sRT. Disease distribution on 18F-DCFPyL PET/CT in patients after salvage PBRT and WPRT was compared using Chi-square tests for independence. Risk factors were tested for association with pelvic LN relapse after RP and after salvage PBRT using logistic regression. Results979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 – 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases in the salvage PBRT (34.5%) and WPRT (46.2%) groups did not differ (p = 0.309). Multiple patient characteristics were associated with pelvic LN disease in the post-RP group, including ISUP grade (Odds Ratio 2.01, p = 0.001) and seminal vesicle invasion (OR 3.85, p = 0.021). ConclusionAt PSA persistence or progression, salvage WPRT in this cohort resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection. MicroAbstractOptimal patient selection for salvage whole pelvic radiotherapy (WPRT) remains uncertain. This study utilized 18F-DCFPyL PET/CT, a novel and highly sensitive imaging modality, to compare disease distribution after prostate bed (PBRT) or WPRT. PBRT resulted in higher rates of pelvic nodal and nodal-only recurrences, indicating that WPRT may benefit patients at higher risk for lymph node disease.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC. Using the 2020 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2019. We selected patients with clinical T2-T4aN0M0 disease receiving CCR as first-line treatment. CCR was defined as transurethral resection of bladder tumor followed by ≥40 Gy radiation to the bladder with concurrent single- or multiple-agent chemotherapy. Based on elective nodal irradiation status, patients were stratified as having received BO-CCR vs. WP-CCR. OS analysis was performed using summary three-month conditional landmark, inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier estimates, and Cox regression. A total of 604 patients receiving CCR for MIBC were identified: 367 (60.8%) BO-CCR and 237 (39.2%) WP-CCR. Before IPTW, the groups were imbalanced in terms of baseline characteristics. The median followup of the weighted population was 42.3 months (interquartile range 18.1-49.1 months). In IPTW-adjusted Cox proportional hazards regression analysis, WP-CCR was associated with a significant OS benefit compared to BO-CCR (adjusted hazard ratio 0.72, 95% confidence interval 0.54-0.96, p=0.026). In the setting of CCR for N0 MIBC, this retrospective NCDB analysis revealed that WP-CCR was associated with a benefit in OS compared to BO-CCR.

Impact of Prophylactic Pelvic Lymph Node Irradiation in De-Novo Oligometastatic Prostate Cancer.

To evaluate the impact of prophylactic pelvic nodal irradiation in de-novo oligometastatic prostate cancer treated with radiotherapy (RT) for both primary tumor and all metastatic lesions. This was a single-center prospective cohort study. De novo oligometastatic prostate cancer patients with RT for both primary tumor and all metastatic lesions were included. Kaplan-Meier method, log rank test and cox regression were used to calculate OS and PFS. PFS included PSA failure, local or distant failure assessed by imaging. This study analyzed 202 patients from 10/2011 to 1/2022 with median follow-up of 48 months. A total of 126 (62.4%) patients were treated with pelvic lymph node RT. The dose was 47.5 Gy with 1.9 Gy per fraction. Among them, 66 (32.7%) patients were treated with whole pelvic RT (WPRT), which the upper limit was at the aortic bifurcation. 60 (29.7%) patients were treated with mini-WPRT, which the upper limit was at the lower margin of obturator foramen. The incidence of diarrhea (P = 0.038) and leukocyte reduction (P = 0.040) in the WPRT subgroup during radiotherapy was significantly higher than that in the mini-WPRT and non-pelvic RT subgroup. For the whole cohort, the median OS and PFS were not reached. The subgroup analysis showed that the elective pelvic nodal irradiation could improve PFS (P = 0.042). However, there was no difference of PFS between standard WPRT and mini-WPRT. The study suggests that for de-novo oligometastatic prostate cancer, elective pelvic nodal irradiation may improve PFS. For patients who cannot tolerate WPRT, mini-WPRT may be an alternative option. However, it needs to be verified in the prospective RCT study.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

AimThe optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.MethodsThis retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.ResultsThree hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.ConclusionFavorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Meta-analysis of Elective Pelvic Nodal Irradiation Using Moderate Hypofractionation for High-Risk Prostate Cancer

Despite several advances in planning and delivery of radiation therapy (RT) for prostate cancer, the role of elective pelvic nodal irradiation (EPNI) remains controversial for high-risk disease. We performed a meta-analysis to evaluate the outcomes of patients treated with moderate hypofractionated RT (MHF-RT) with EPNI using modern RT techniques. Eligible studies were identified on MEDLINE, Embase, the Cochrane Library, and proceedings of annual meetings through October 2021. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. A metaregression analysis was performed to assess a possible correlation between selected variables and outcomes. A P value <.05 was considered significant. Eighteen studies with a total of 1745 patients (median follow-up, 61 months) treated with EPNI using MHF-RT were included. The biochemical relapse-free survival at 5, 7, and 10 years was 90% (95% confidence interval [CI], 88%-94%), 83% (95% CI, 78%-91%), and 78% (95% CI, 68%-88%). The 5-year prostate cancer-specific survival, disease-free survival, distant metastases-free survival, and overall survival were 98% (95% CI, 97%-99%), 88.7% (95% CI, 85%-93%), 91.2% (95% CI, 88%-92%), and 93% (95% CI, 90%-96%), respectively. The rates of local, pelvic, and distant recurrence were 0.38% (95% CI, 0%-2%), 0.13% (95% CI, 0%-1.5%), and 7.35% (95% CI, 2%-12%), respectively. The rate of late grade ≥2 gastrointestinal and genitourinary toxic effects were 6.7% (95% CI, 4%-9%) and 11.3% (95% CI, 7.6%-15%), with heterogeneity, but with rare cases of grade 3 to 5 toxic effects. EPNI with concomitant MHF-RT provides satisfactory biochemical relapse-free survival in long-term follow-up, with low rates of genitourinary and gastrointestinal severe toxic effects and minimal pelvic and local failure.

Elective Pelvic Nodal Irradiation With A Simultaneous Hypofractionated Integrated Prostate Boost for Localized High Risk Prostate Cancer: Long Term Results From a Prospective Clinical Trial

To report on the long-term results of patients with localized high risk prostate cancer treated with elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost along with adjuvant androgen deprivation therapy (ADT).This was a prospective single-institution single-arm phase II study. Patients with high-risk prostate cancer (any of cT3 disease, PSA > 20 ng/mL, or Gleason score 8-10) were eligible. Patients underwent radiotherapy to a dose of 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous image-guided (matched to prostatic fiducial markers) IMRT boost of 22.5 Gy to the prostate for a total of 67.5 Gy in 25 fractions (2.7 Gy per fraction) over 5 weeks. Patients were to receive ADT for 2-3 years. Endpoints included biochemical failure (Phoenix definition), distant radiographic failure, and overall survival. Univariate and multivariable analyses were performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0 for 5 years.Two hundred thirty patients (median age 71 years) were enrolled from 2004-2010. Median follow-up was 11.2 years (IQR 8.1-12.9). 67% of patients had Gleason score ≥ 8, 44% had PSA > 20 ng/mL, and 27% had cT3 disease. Median ADT duration was 30 months (IQR 21-33). Median PSA nadir was 0.02 ng/mL (IQR 0.02-0.02). Cumulative incidence of testosterone recovery (> 1.7 nmol/L) was 47.6% and 77.5% at 5 and 10 years, respectively. Cumulative incidence of biochemical failure was 15% and 33.4% at 5 and 10 years, respectively. At 10 years, the cumulative incidence of distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir > 0.05 ng/mL was predictive of biochemical failure (HR 6.8, 95% CI 4-11.8, P < 0.001) and development of distant metastases (HR 7.5, 95% CI 3.9-14.5, P < 0.0001). PSA nadir > 0.1 ng/mL (HR 5.2, 95% 2.2-12, P = 0.0001) and ADT use < 12 months (versus > 24 months) (HR 2.3, 95% CI 1.3-3.9, P = 0.004) were predictive of worse survival. The 5-year cumulative incidence of any late grade ≥ 3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.This was a large prospective study evaluating EPNI and a simultaneous hypofractionated prostate boost over 5 weeks combined with 2-3 years of ADT for localized high risk prostate cancer with very mature follow-up. Ten-year biochemical control and overall survival rates were favorable. Lower PSA nadir predicted for higher biochemical control, less distant failure, and longer overall survival. ADT duration of ≤ 12 months was associated with decreased overall survival.

Salvage hypofractionated accelerated versus standard radiotherapy for the treatment of biochemical recurrence after radical prostatectomy (SHARE): the protocol of a prospective, randomized, open-label, superiority, multi-institutional trial

BackgroundWhile several phase III trials have investigated the role of hypofractionated radiotherapy in the definitive treatment of localized prostate cancer, prospective data reporting the outcomes of hypofractionated radiotherapy in the postoperative treatment setting are sparse. Therefore, this study is designed to assess the efficacy and treatment-related toxicity of hypofractionated salvage radiotherapy for the treatment of biochemical recurrence in men who underwent radical prostatectomy. The primary objective of this trial is to investigate whether hypofractionated radiotherapy improves biochemical control compared with conventionally fractionated radiotherapy. In addition, treatment-related toxicity, quality of life, and survival will be evaluated as secondary endpoints.MethodsIn this prospective, randomized, multi-institutional trial (the SHARE study), patients with intermediate- or high-risk prostate cancer will be randomized to receive either hypofractionated radiotherapy (65 Gy in 2.5-Gy fractions) or conventionally fractionated radiotherapy (66 Gy in 2-Gy fractions). Prostate bed irradiation or elective pelvic nodal irradiation including the prostate bed will be performed using intensity-modulated radiotherapy and daily image guidance. Treatment efficacy will be assessed using the serum tumor marker prostate-specific antigen, and toxicity will be evaluated through both physician- and patient-reported outcomes. Quality of life will also be investigated.DiscussionThis study is designed to demonstrate whether hypofractionated radiotherapy is beneficial in terms of biochemical control and toxicity compared with standard salvage radiotherapy. If hypofractionated radiotherapy is shown to be superior to conventionally fractionated radiotherapy, it will mean that improved biochemical control can be achieved, accompanied by greater patient convenience and more efficient use of medical resources.Trial registrationClinicalTrials.gov NCT03920033. Registered on 18 April 2019

1: Elective Pelvic Nodal Irradiation with a Simultaneous Hypofractionated Integrated Prostate Boost for Localized High Risk Prostate Cancer: Long Term Results from a Prospective Clinical Trial

1: Elective Pelvic Nodal Irradiation with a Simultaneous Hypofractionated Integrated Prostate Boost for Localized High Risk Prostate Cancer: Long Term Results from a Prospective Clinical Trial

Elective pelvic nodal irradiation with a simultaneous hypofractionated integrated prostate boost for localized high risk prostate cancer: Long term results from a prospective clinical trial

BackgroundTo report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer. Materials and methodsThis was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8–10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2–3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0. Results230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1–12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4–11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9–14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2–12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3–3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively. ConclusionEPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.

Long-Term Results of a Prospective Phase 2 Study on Volume De-Escalation in Neoadjuvant Chemoradiotherapy of Rectal Cancer

PurposeIn the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. Methods and MaterialsPatients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. ResultsFifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. ConclusionsDe-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Elective Pelvic Nodal Irradiation With a Simultaneous Hypofractionated Integrated Prostate Boost for Localised Prostate Cancer: Ready for Prime Time?

External beam radiotherapy is a standard treatment option for localised prostate cancer and hypofractionation has become an alternative to conventionally fractionated radiotherapy. In patients who receive external beam radiotherapy, elective pelvic nodal irradiation is sometimes delivered, especially in patients with unfavourable disease who are at risk of micrometastatic spread of cancer into the regional nodes. One elegant approach to combine prostate hypofractionation with elective pelvic nodal irradiation is with a simultaneous integrated boost technique, where a radical hypofractionated dose is delivered to the prostate while the regional pelvic nodes receive a lower microscopic dose simultaneously in a single radiotherapy plan over the same number of treatment fractions. This article reviews the existing published literature evaluating such an approach.

Postoperative elective pelvic nodal irradiation compared to prostate bed irradiation in locally advanced prostate cancer \u2013 a retrospective analysis of dose-escalated patients

BackgroundIt is uncertain if whole-pelvic irradiation (WPRT) in addition to dose-escalated prostate bed irradiation (PBRT) improves biochemical progression-free survival (bPFS) after prostatectomy for locally advanced tumors. This study was initiated to analyze if WPRT is associated with bPFS in a patient cohort with dose-escalated (> 70 Gy) PBRT.MethodsPatients with locally advanced, node-negative prostate carcinoma who had PBRT with or without WPRT after prostatectomy between 2009 and 2017 were retrospectively analyzed. A simultaneous integrated boost with equivalent-doses-in-2-Gy-fractions (EQD-2) of 79.29 Gy or 71.43 Gy to the prostate bed was applied in patients with margin-positive (or detectable) and margin-negative/undetectable tumors, respectively. WPRT (44 Gy) was offered to patients at an increased risk of lymph node metastases.ResultsForty-three patients with PBRT/WPRT and 77 with PBRT-only were identified. Baseline imbalances included shorter surgery-radiotherapy intervals (S-RT-Intervals) and fewer resected lymph nodes in the WPRT group. WPRT was significantly associated with better bPFS in univariate (p = 0.032) and multivariate models (HR = 0.484, p = 0.015). Subgroup analysis indicated a benefit of WPRT (p = 0.029) in patients treated with rising PSA values who mostly had negative margins (74.1%); WPRT was not associated with a longer bPFS in the postoperative setting with almost exclusively positive margins (96.8%).ConclusionWe observed a longer bPFS after WPRT compared to PBRT in patients with locally advanced prostate carcinoma who underwent dose-escalated radiotherapy. In subset analyses, the association was only observed in patients with rising PSA values but not in patients with non-salvage postoperative radiotherapy for positive margins.

Patterns of Recurrence After Salvage Radiotherapy Encompassing Pelvic Lymphatics in Men with High-risk Prostate Cancer.

The efficacy of adjuvant or salvage radiation to the regional lymph node area has not been fully investigated in high-risk prostate cancer patients; instead, radiotherapy is limited to the prostate fossa. The present study aimed to assess patterns of recurrence in prostate cancer patients with biochemical failure (BCF) who were treated with whole-pelvic salvage radiotherapy (SRT) following radical prostatectomy. The clinical data from 196 high-risk prostate cancer patients who received SRT for BCF after radical prostatectomy were reviewed. BCF after SRT was detected in 80 patients, and 59 patients underwent imaging studies. Twenty four recurrences in 16 patients were identified, including 13 bone metastases, 6 vesicourethral anastomosis site recurrences, and 5 lymph node recurrences (one simultaneous with vesicourethral anastomosis). Regarding the treatment field, no in-field nodal recurrence was observed, whereas 4 out-of-field and 1 edge-of-field recurrences were detected. Locoregional recurrence was most common at the anastomosis site. Most nodal recurrences were located outside the pelvis, suggesting that elective pelvic nodal irradiation should be recommended in a selected patient population.

Outcomes and toxicity of 313 prostate cancer patients receiving helical tomotherapy after radical prostatectomy

PurposeThere are limited long-term data on patients treated with image guided intensity modulated radiation therapy (IG-IMRT) for prostate cancer recurrence or high-risk disease features after radical prostatectomy. We report single-institution results for patients treated with IG-IMRT and identify variables associated with outcome. Methods and materialsThis is a retrospective chart review consisting of 313 consecutive patients who were treated with adjuvant or salvage IG-IMRT from 2004 to 2013. Cox proportional hazards analysis was used to identify factors related to survival and toxicity. Toxicity was graded using the Common Terminology Criteria for Adverse Events Version 4.0. ResultsThe median follow-up was 55 months (range, 6-131 months). The median pre-radiation therapy (RT) prostate-specific antigen (PSA) was 0.3 ng/mL (range, <0.01-55.4). The vast majority of patients (87%) received elective pelvic nodal irradiation (median dose: 45 Gy). Androgen deprivation therapy (ADT) was given to 39% of patients for a median of 9 months. Five-year biochemical progression-free survival and distant metastasis-free survival were 59% (95% confidence interval, 53%-66%) and 89% (95% confidence interval, 85%-93%), respectively. On multivariate analysis, higher pre-RT PSA (>0.2 ng/mL), biopsy Gleason score (≥7 [4+3]), and duration of ADT (>6 months) were significantly associated (P < .05) with biochemical progression-free survival. Actuarial late grade 3 genitourinary and gastrointestinal toxicities at 5 years were 10% and 2%, respectively. ConclusionOur results suggest that lower pre-RT PSA level and longer duration of ADT are associated with improved biochemical control. The incidence of late grade 3 gastrointestinal toxicity was low, but late grade 3 genitourinary toxicity was higher than anticipated.

The Re-Emerging Role of Elective Pelvic Nodal Irradiation in High-Risk Node Negative Prostate Cancer

The benefit of elective nodal irradiation (ENI) in combination with androgen deprivation therapy in high risk localized node negative prostate cancer has yet to be clearly defined. The potential gains in local control have been offset by the increased toxicity associated with pelvic radiotherapy, and recognition that historically the only trials to demonstrate a survival advantage in this group have been with androgen deprivation therapy. This review article considers the impact of pivotal randomized clinical trials conducted over the last thirty years on routine clinical practice, and how modern techniques may help to redefine radiotherapy as a necessary component for this group of patients.

Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients.

AimOur aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol.Material and methodA total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course.ResultsThe first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups.ConclusionTreating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity.

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.

PV-0378: CBCT derived CTV-PTV margins for elective pelvic node irradiation of prostate cancer patients

PV-0378: CBCT derived CTV-PTV margins for elective pelvic node irradiation of prostate cancer patients

Dosimetric Correlates for Acute Toxicity in Prostate Cancer Treated With Hypofractionated Radiation Therapy: Absolute Volumes Are Better Predictors Than Relative Volumes

Purpose/Objective(s)Hypofractionated radiation therapy is becoming a widely accepted approach in the treatment of prostate cancer. This retrospective study reports acute toxicity and the dosimetric correlates of a cohort of patients treated at a single centre in India.Materials/MethodsOne hundred one patients with localized prostate cancer were treated with image guided intensity modulated radiation therapy (IG- IMRT) between July 2011 and Jan 2014. Two different fractionation schedules were used, with 65Gy/25Fr/ 5 weeks being used in the first 18 patients (EQD2 76Gy a/b = 1.5) and the subsequent 83 being treated with 60Gy/20Fr/4 weeks schedule(77.2Gy a/b = 1.5). Majority of them (n = 83, 83.2%) had high risk or pelvic node positive disease and received elective pelvic nodal irradiation (44Gy/20Fr or 45 Gy/25Fr) using a single phase plan with simultaneous integrated boost to the prostate and seminal vesicles (SV). The prostate +/- SV were treated using a PTV margins of 7 mm and nodal regions were given a margin of 5 mm. Rectum and bladder were contoured as whole organ volumes. All of the patients were assessed weekly during treatment and their acute toxicities recorded using RTOG acute morbidity scoring criteria. Receiver operating characteristic (ROC) curves were generated to identify dose thresholds for acute rectal and bladder toxicity.ResultsAll patients completed their entire course of the intended treatment and the schedules were well tolerated. There were no Grade 3 or 4 gastrointestinal (GI) or genitourinary(GU) toxicity. The incidence of acute Grade 1 and 2 GI toxicity was 48.5% and 18.8%, while grade 1 and 2 acute GU acute toxicity was 50.5% and 6% respectively. Small bowel toxicity was negligible (Gr 1 - 12.9% and Gr 2 = 4%). There were no significant differences in the incidence of toxicities between the two fractionation schedules. We analysed the 2 Gy equivalent (EQD2) doses to the rectum and bladder (assuming α/β = 3), and found that the absolute doses were better predictors acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V EQD2 60Gy (13.1cc vs 10cc, p = 0.013) and V EQD2 50Gy (20.7cc vs 15.5cc, p = 0.007). The patients with Grade 2 more GU symptoms had significantly higher V EQD2 70Gy (33.6cc vs 18.3cc, p = <0.01) and V EQD2 50Gy (46cc vs 28.8cc, p = 0.001). The optimal cut off value for predicting Grade 2 proctitis, obtained from ROC curves for V EQD2 60Gy was 9.7 cc and for V EQD2 50Gy was 17.1 cc. For Grade 2 GU symptoms, the threshold values were V EQD2 70Gy 23.6cc and VEQD2 65Gy 38.1cc.ConclusionsHypofractionated radiation therapy for prostate cancer is well tolerated and associated with manageable acute side-effects. The absolute dose volume parameters of rectum and bladder predict for acute toxicities. Purpose/Objective(s)Hypofractionated radiation therapy is becoming a widely accepted approach in the treatment of prostate cancer. This retrospective study reports acute toxicity and the dosimetric correlates of a cohort of patients treated at a single centre in India. Hypofractionated radiation therapy is becoming a widely accepted approach in the treatment of prostate cancer. This retrospective study reports acute toxicity and the dosimetric correlates of a cohort of patients treated at a single centre in India. Materials/MethodsOne hundred one patients with localized prostate cancer were treated with image guided intensity modulated radiation therapy (IG- IMRT) between July 2011 and Jan 2014. Two different fractionation schedules were used, with 65Gy/25Fr/ 5 weeks being used in the first 18 patients (EQD2 76Gy a/b = 1.5) and the subsequent 83 being treated with 60Gy/20Fr/4 weeks schedule(77.2Gy a/b = 1.5). Majority of them (n = 83, 83.2%) had high risk or pelvic node positive disease and received elective pelvic nodal irradiation (44Gy/20Fr or 45 Gy/25Fr) using a single phase plan with simultaneous integrated boost to the prostate and seminal vesicles (SV). The prostate +/- SV were treated using a PTV margins of 7 mm and nodal regions were given a margin of 5 mm. Rectum and bladder were contoured as whole organ volumes. All of the patients were assessed weekly during treatment and their acute toxicities recorded using RTOG acute morbidity scoring criteria. Receiver operating characteristic (ROC) curves were generated to identify dose thresholds for acute rectal and bladder toxicity. One hundred one patients with localized prostate cancer were treated with image guided intensity modulated radiation therapy (IG- IMRT) between July 2011 and Jan 2014. Two different fractionation schedules were used, with 65Gy/25Fr/ 5 weeks being used in the first 18 patients (EQD2 76Gy a/b = 1.5) and the subsequent 83 being treated with 60Gy/20Fr/4 weeks schedule(77.2Gy a/b = 1.5). Majority of them (n = 83, 83.2%) had high risk or pelvic node positive disease and received elective pelvic nodal irradiation (44Gy/20Fr or 45 Gy/25Fr) using a single phase plan with simultaneous integrated boost to the prostate and seminal vesicles (SV). The prostate +/- SV were treated using a PTV margins of 7 mm and nodal regions were given a margin of 5 mm. Rectum and bladder were contoured as whole organ volumes. All of the patients were assessed weekly during treatment and their acute toxicities recorded using RTOG acute morbidity scoring criteria. Receiver operating characteristic (ROC) curves were generated to identify dose thresholds for acute rectal and bladder toxicity. ResultsAll patients completed their entire course of the intended treatment and the schedules were well tolerated. There were no Grade 3 or 4 gastrointestinal (GI) or genitourinary(GU) toxicity. The incidence of acute Grade 1 and 2 GI toxicity was 48.5% and 18.8%, while grade 1 and 2 acute GU acute toxicity was 50.5% and 6% respectively. Small bowel toxicity was negligible (Gr 1 - 12.9% and Gr 2 = 4%). There were no significant differences in the incidence of toxicities between the two fractionation schedules. We analysed the 2 Gy equivalent (EQD2) doses to the rectum and bladder (assuming α/β = 3), and found that the absolute doses were better predictors acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V EQD2 60Gy (13.1cc vs 10cc, p = 0.013) and V EQD2 50Gy (20.7cc vs 15.5cc, p = 0.007). The patients with Grade 2 more GU symptoms had significantly higher V EQD2 70Gy (33.6cc vs 18.3cc, p = <0.01) and V EQD2 50Gy (46cc vs 28.8cc, p = 0.001). The optimal cut off value for predicting Grade 2 proctitis, obtained from ROC curves for V EQD2 60Gy was 9.7 cc and for V EQD2 50Gy was 17.1 cc. For Grade 2 GU symptoms, the threshold values were V EQD2 70Gy 23.6cc and VEQD2 65Gy 38.1cc. All patients completed their entire course of the intended treatment and the schedules were well tolerated. There were no Grade 3 or 4 gastrointestinal (GI) or genitourinary(GU) toxicity. The incidence of acute Grade 1 and 2 GI toxicity was 48.5% and 18.8%, while grade 1 and 2 acute GU acute toxicity was 50.5% and 6% respectively. Small bowel toxicity was negligible (Gr 1 - 12.9% and Gr 2 = 4%). There were no significant differences in the incidence of toxicities between the two fractionation schedules. We analysed the 2 Gy equivalent (EQD2) doses to the rectum and bladder (assuming α/β = 3), and found that the absolute doses were better predictors acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V EQD2 60Gy (13.1cc vs 10cc, p = 0.013) and V EQD2 50Gy (20.7cc vs 15.5cc, p = 0.007). The patients with Grade 2 more GU symptoms had significantly higher V EQD2 70Gy (33.6cc vs 18.3cc, p = <0.01) and V EQD2 50Gy (46cc vs 28.8cc, p = 0.001). The optimal cut off value for predicting Grade 2 proctitis, obtained from ROC curves for V EQD2 60Gy was 9.7 cc and for V EQD2 50Gy was 17.1 cc. For Grade 2 GU symptoms, the threshold values were V EQD2 70Gy 23.6cc and VEQD2 65Gy 38.1cc. ConclusionsHypofractionated radiation therapy for prostate cancer is well tolerated and associated with manageable acute side-effects. The absolute dose volume parameters of rectum and bladder predict for acute toxicities. Hypofractionated radiation therapy for prostate cancer is well tolerated and associated with manageable acute side-effects. The absolute dose volume parameters of rectum and bladder predict for acute toxicities.

When is Elective Pelvic Lymph Node Irradiation Indicated in Definitive Radiotherapy for Localized Prostate Cancer?

The objective is to define the role of elective pelvic node irradiation (EPNI) in patients treated with definitive radiotherapy for clinically localized prostate cancer. Review of the pertinent literature revealed few prospective randomized trials that evaluated the efficacy of EPNI. Although EPNI may reduce the risk of regional recurrence, its impact on biochemical progression-free survival and overall survival is unclear. Depending on the extent of the radiotherapy fields, EPNI may result in a modest increase in acute toxicity and an even smaller increase in late toxicity. EPNI may reduce the risk of regional failure in patients with high-risk prostate cancer with a likelihood of lymph node positivity of ≥15%. Although it may result in improved biochemical progression-free survival, its impact is likely modest, at best. However, EPNI should be considered for patients with a high risk of regional disease.