Salvage intensity-modulated radiotherapy for rising PSA after radical prostatectomy (original) (raw)
Related papers
Clinical Toxicities and Dosimetric Parameters after Whole-Pelvis versus Prostate Bed-only Intensity
Fuel and Energy Abstracts, 2010
Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinal (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicityfree survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median followup of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity. Ó
Radiotherapy and Oncology, 2010
Purpose/objective: Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity. Materials and methods: Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves. Results: 15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL P 50 cc, V50TL P 13 cc, V55TL P 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (P13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009). Conclusions: The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.
Strahlentherapie und Onkologie, 2006
Purpose: 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. Patients and Methods: 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). Results: 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. Conclusion: Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.
Radiotherapy and Oncology, 2009
Purpose: To investigate the role of IMRT in reducing the risk of acute genito-urinary (GU), upper gastrointestinal (uGI) and lower gastrointestinal (lGI) toxicity following whole-pelvis irradiation (WPRT) after radical prostatectomy. Patients and methods: 172 consecutive patients with prostate cancer were post-operatively irradiated to the prostatic bed (PB) and pelvic lymph-nodal area with adjuvant (n = 100) or salvage (n = 72) intent. Eighty-one patients underwent three-dimensional conformal (3DCRT) WPRT, while the remaining 91 underwent IMRT (54/91 with helical tomotherapy (HTT); 37/91 with Linac intensity-modulated RT (Lina-cIMRT)). Results: Patients treated with IMRT experienced a decreased risk of acute toxicity. The crude incidence of grade P2 toxicity was GU 12.3% vs. 6.6% (p = 0.19); lGI 8.6% vs. 3.2% (p = 0.14); uGI 22.2% vs. 6.6% (p = 0.004), for 3DCRT and IMRT, respectively. With respect to uGI and lGI, the acute toxicity profile of the HTT patients was even better when compared to that of 3DCRT patients (crude incidence:1.8% and 0.0%, respectively). Treatment interruptions due to uGI toxicity were 11/81 in the 3DCRT group vs. 2/ 91 in the IMRT group (p = 0.006). Conclusions: The risk of acute toxicity following post-operative WPRT delivered by means of IMRT was reduced compared to that of 3DCRT. The most significant reduction concerned uGI, mainly owing to better bowel sparing with IMRT.
International Journal of Radiation Oncology*Biology*Physics, 2012
Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V 70 ), 65 Gy (V 65 ), and 40 Gy (V 40 ). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V 70 #10%, V 65 #20%, and V 40 #40%; 92% for men with rectal V 70 #20%, V 65 #40%, and V 40 #80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged $70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity. Ó 2012 Elsevier Inc.
Journal of Clinical Oncology, 2018
The ASCO/Cancer Care Ontario (CCO) joint guidelines recommend that patients with unfavorable intermediate-to high-risk prostate cancer should be offered combined brachytherapy when receiving external-beam radiation therapy (EBRT) and that there may be increased genitourinary (GU) toxicity compared with EBRTalone. 1 The recommendation was based on three phase III trials demonstrating clinical improvement. 2-5 Spratt and Carroll, 6 in a recent Comments and Controversies article, criticized this recommendation. On behalf of the American Brachytherapy Society and the American Radium Society Appropriate Use Criteria Genitourinary Committee, we endorse the ASCO/CCO joint guidelines and wish to address the arguments presented in the article. With dose escalation provided by the addition of brachytherapy to EBRT, increased urinary toxicity may be expected but not to the extent that Spratt and Carroll 6 suggest. Regarding toxicity from the ASCENDRE-RT (Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy) trial, their commentary elided the difference between cumulative and point prevalence of late toxicity. The authors overstated the increased 5-year cumulative late grade $ 3 GU toxicity in the combination brachytherapy arm versus the EBRTalone arm, which was mostly composed of urethral strictures. These strictures were attributed to overestimating the inferior extent of the prostatic apex, resulting in treatment of the GU diaphragm, which is not commonly practiced in the current era of treatment planning with high-quality magnetic resonance imaging. Because many complications resolved, the prevalence (proportion of patients still experiencing toxicity) of grade $ 3 GU toxicity in ASCENDE-RT was much diminished, at , 10% in both arms (P 5 .06). 7 This prevalence rate is markedly less than the reported grade $ 3 incontinence rate (17% to 70%), impotence rate (80%), and stricture rate (10%) after radical prostatectomy in phase III studies including the PROTECT (Prostate Testing for Cancer and Treatment), PIVOT (Prostate Cancer Intervention Versus Observation Trial), and SPCG4 (Scandinavian Prostate Cancer Group Study Number 4) trials and in the Cancer of the Prostate Strategic Urologic Research Endeavor database. Despite these facts, the authors concluded that the "adverse effects in the ASCENDE-RT trial [combination arm] were of much greater concern than that between EBRT and surgery." 6 In analyzing the phase III trial by Hoskin et al, 4 the article omitted data demonstrating no difference in cumulative late
Brachytherapy, 2011
PURPOSE: To describe biochemical relapse-free survival (BRFS) and late toxicity after combined highedose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate-and high-risk prostate cancer patients. METHODS AND MATERIALS: From March 2003 to September 2005, 64 men were treated by 3 Â 7 Gy HDR-B using one implant followed by 50 Gy IMRT. Median age was 66.1 years; risk of recurrence was intermediate in 30 (47%) or high in 34 (53%) patients. Forty-four (69%) patients received hormonal therapy. Patients were treated with a median of 13 HDR-B applicators (range, 8e17). Biochemical relapse was defined according to Phoenix criteria. Toxicity was scored according to the Common Toxicity Criteria scale version 3.0. RESULTS: Median followup was 5.1 years. The 3-year BRFS was 100% and 91% for intermediate-and high-risk patients. Late Grade 2 gastrointestinal (GI) toxicity occurred in 3 (4.7%) patients, late Grade 3 GI toxicity was absent. Late Grade 3 and 4 genitourinary (GU) toxicity was observed in 7 (10.9%) and 2 (3.1%) patients. The 5-year Grade 3 or higher late GU toxicity-free survival was associated with a higher number of HDR-B applicators (p 5 0.049). CONCLUSIONS: The 3-year BRFS was excellent and late GI toxicity was negligible. However, the late Grade 3 and 4 GU toxicity was unacceptably high.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: To evaluate the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of postoperative radiotherapy (RT) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 or positive surgical margins after RP were treated with RT plus 2 years of androgen suppression, according to a Phase II study. Acute and late GI and GU toxicity was prospectively assessed using the National Cancer Institute's Expanded Common Toxicity Criteria, version 2.0. The incidence of late GI and GU toxicity was estimated using a cumulative incidence method. A Cox proportional regression analysis was performed to evaluate the predictive factors for late toxicity. Results: The median patient age was 61 years at RP. The median interval between RP and postoperative RT was 4.2 months. The median follow-up was 42.4 months. Of the 78 patients, 76 and 74 were available for the acute and late toxicity analysis, respectively. Of these patients, 66%, 29%, and 1% experienced Grade 1, 2, and 3 acute GI or GU toxicity, respectively. The cumulative incidence of Grade 2 or greater and Grade 3 or greater late GI toxicity at 36 months was 8.1% and 0%, respectively. The cumulative incidence of Grade 2 or greater and Grade 3 or greater late GU toxicity at 36 months was 16.4% and 2.7%, respectively. None had Grade 4 or greater late toxicity. The severity of acute GU toxicity (less than Grade 2 vs. Grade 2 or greater) was a significant predictor factor for Grade 2 or greater late GU toxicity after adjusting for pre-existing GU dysfunction. Conclusions: Postoperative RT was generally well tolerated. Grade 3 or greater late GI or GU toxicity was uncommon. Ó 2008 Elsevier Inc.
European Urology, 2011
Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormoneereleasing hormone analog. The duration and indication of ADTwas left at the discretion of the treating physician. The effect of HD-ARTand ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient-and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p Z 0.02) and cRFS (HR 0.2, p Z 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p Z 0.009). The 7-year probability of late Grade 2e3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT.
Late GI and GU complications in the treatment of prostate cancer
1997
Purpose: To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate. Methods and Materials: Seven hundred twelve consecutive prostate cancer patients treated at this in&t&ion between 19% and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or pro&is. Late Grade 3 GU morbidity was cyst&is or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects 2 Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP). Results: Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side ef&ts acutely. Late and acute morbiditles were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GLJ morbiditks occurred signiticantly later (mean: 22.7 months). Central axis dose was the only independent variable s&&lean@ related to the incidence of late GI morbidity on MVA. No treatment volume parameters were sign&ant for Grade 3. The following parameters were siguiflcantly related (by MVA) to Grade 2 GI morbid&y: central axis dose, use of the increased rectal shiehling, androgen deprivation therapy starting before RT. Acute and l&e GI morbidlties were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were sig&lcantly related to acute GX side effects. The parameters signllicantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivarlate analysis. Acute GU side effects were highly correlated with late GU injury. The fstlio~hg were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (-), TURP before RT (-), presentation with urinary obstructive symptoms. Conclusion: Both late GI and GU morbidity demonstrate a dose dependence, but only the vohnne dependence observed is a reduction in late Grade 2-4 GI morbidity by increasing the rectal shielding in the l&era1 fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence. Copyright 0 1997 Elsevier Science Inc.