Multicenter, dual fractionation scheme, single core lab comparison of rectal volume dose reduction following injection of two biodegradable perirectal spacers.

PURPOSE: A multicenter, double-arm, central core lab, retrospective study was performed to compare the rectal dosimetry of patients implanted with two injectable, biodegradable perirectal spacers, in conventional fractionation (CF), as well as ultrahypofractionation (UH) treatment plans. METHODS AND MATERIALS: Fifty-nine patients were enrolled into the study in five centers: two centers in Europe, which implanted a biodegradable balloon spacer in a total of 24 subjects and three centers in the US, which implanted the SpaceOAR in 35 subjects. Anonymized CTs (pre and post-implantation) were reviewed by the central core lab. For VMAT CF plans rectal V50, V60, V70, and V80 were calculated. For UH plans, a corresponding rectal V22.6, V27.1, V31.37, and V36.25 were established representing 62.5%, 75%, 87.5%, and 100% of the 36.25 Gy prescribed dose. RESULTS: For CF VMAT, a comparison between the balloon spacer and the SpaceOAR revealed a significant difference of 33.4% decrease in mean rectal V50 (71.9% vs. 38.5%, p < 0.001), 27.7% in mean rectal V60 (79.6% vs. 51.9%, p < 0.001), 17.1% difference in mean rectal V70 (84.1% vs. 67.0%, p = 0.001), and a significant difference of 3.0% (p = 0.019) in mean rectal V80 (87.2% vs. 84.2%). With UH analysis, the mean rectal dose reduction for the balloon spacer compared to the SpaceOAR was 79.2% and 53.3% for V27.1 (p < 0.001), 84.1% and 68.1% for V31.71 (p = 0.001), and 89.7% and 84.8% for V36.25 (p = 0.012), respectively. CONCLUSION: Rectal dosimetry is more favorable for treatment with the balloon spacer compared with SpaceOAR. Further research, particularly in the context of a prospective randomized clinical trial design, is needed to assess the acute and late toxicity experience as well as physician satisfaction with achieving symmetrical implantation, and ease of use in light of increasing clinical use.

Utilization trends in prostate cancer therapy.

PURPOSE: We determined therapeutic trends in the management of adenocarcinoma of the prostate, and in the case of intensity modulated radiation therapy we investigated whether site of service influenced those trends. MATERIALS AND METHODS: A variety of CPT codes to treat adenocarcinoma of the prostate were extracted from the Medicare Part B 5% sample for the years 2006 to 2008 inclusive. Data were stratified by year, type of service and, in the case of radiation therapy, site of service. Treatment trends were calculated by indexing the total number of Medicare beneficiaries receiving a service against needle biopsies of the prostate. RESULTS: The percentage of Medicare beneficiaries receiving therapy indexed to needle biopsies of the prostate increased from 43.8% in 2006 to 49.0% in 2008. Trends in radiation and surgery were similar with 11.5% and 13% increases in each modality, respectively. Total Medicare beneficiaries receiving intensity modulated radiation therapy and laparoscopic radical prostatectomy increased by 25.4% and 22.1%, respectively, while Medicare beneficiaries treated with open radical prostatectomy and 3-dimensional conformal radiation therapy decreased by 27.9% and 37.6%, respectively. The pattern of use for intensity modulated radiation therapy was similar in physician office and hospital facility settings, increasing from 7.3% to 11.1% and 8.3% to 11.3% of Medicare beneficiaries indexed to needle biopsies of the prostate receiving intensity modulated radiation therapy at these sites in 2008, respectively. CONCLUSIONS: Treatment trends in surgery and radiation strongly favor newer technologies, and in the case of intensity modulated radiation therapy, utilization trends for treatment of adenocarcinoma of the prostate are similar across all sites of service.

Who Benefits From a Prostate Rectal Spacer? Secondary Analysis of a Phase III Trial.

PURPOSE: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit. METHODS AND MATERIALS: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical benefit and plan quality. Mean bowel QOL was assessed at 15 and 36 months posttreatment and the likelihood of 1× (5 points) or 2× (10 points) minimally important difference changes were assessed. RESULTS: Rectal V70 was correlated with physician scored toxicity (P = .033) and was used as a surrogate for plan quality. There was no correlation between prostate volume and rectal V70 (r = 0.077). Rectal V70 pre- and post-hydrogel was 13% and 3% for the smallest prostates (<40 mL) and 12% and 2% for the largest (>80 mL). The relative reduction in rectal V70 of 78% did not vary by prespacer V70, but the absolute reduction was greater for a higher V70. All spacer plans met the 5 QUANTEC rectal dose constraints, although 92% of control plans met all constraints. At 3 years, those not meeting all QUANTEC goals had a 15.0-point (standard deviation 15.1) decline, control patients meeting QUANTEC goals had a 4.0-point (9.5) decline, and spacer had >0.5 (7.6; P < .01). Previous surgery was not correlated with QOL (P = .8). Across prognostic groups, including age, body mass index, previous surgery, target volume, or quality of radiation plans, there was no statistically significant heterogeneity in the relative benefit of spacer in decreasing the risk of 1× or 2× the minimally important difference declines. CONCLUSIONS: There was little heterogeneity in the likelihood of spacer reducing the risk of declines in bowel QOL across clinical and dosimetric variables. Even for the >95% of plans meeting QUANTEC rectal criteria, hydrogel spacer provided potentially meaningful benefits.

Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: Secondary analysis of a phase 3 trial.

BACKGROUND: We previously reported the results of a phase 3 trial evaluating a prostate/rectal hydrogel spacer during prostate intensity modulated radiation therapy, which resulted in decreased rectal dose and toxicity and less decline in bowel quality of life (QOL). A secondary analysis was performed to correlate penile bulb dose and sexual QOL. METHODS AND MATERIALS: Sexual QOL was measured with the Expanded Prostate Cancer Index Composite (EPIC) by mean scores, the proportion of patients with a minimal clinically important difference (MID), and analyses of the different items composing the sexual domain. RESULTS: A total of 222 men enrolled with median follow-up of 37 months. Hydrogel reduced penile bulb mean dose, maximum dose, and percentage of penile bulb receiving 10 to 30 Gy (all P < .05) with mean dose indirectly correlated with erections sufficient for intercourse at 15 months (P = .03). Baseline EPIC was low (53 [standard deviation ± 24]) with no difference between arms (P > .1). A total of 41% (88/222) of men had adequate baseline sexual QOL (EPIC >60 (mean, 77 [± 8.3]). This subgroup at 3 years had better sexual function (P = .03) with a spacer with a smaller difference in sexual bother (P = .1), which resulted in a higher EPIC summary on the spacer arm (58 [±24.1] vs control 45 [± 24.4]) meeting threshold for MID without statistical significance (P = .07). There were statistically nonsignificant differences favoring spacer for the proportion of men with MID and 2× MID declines in sexual QOL with 53% vs 75% having an 11-point decline (P = .064) and 41% vs 60% with a 22-point decline (P = .11). At 3 years, more men potent at baseline and treated with spacer had "erections sufficient for intercourse" (control 37.5% vs spacer 66.7%, P = .046) as well as statistically higher scores on 7 of 13 items in the sexual domain (all P < .05). CONCLUSIONS: The use of a hydrogel spacer decreased dose to the penile bulb, which was associated with improved erectile function compared with the control group based on patient-reported sexual QOL.

Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial.

PURPOSE: SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. METHODS AND MATERIALS: Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. RESULTS: The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). CONCLUSIONS: The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

Urinary quality of life outcomes in men who were treated with image-guided intensity-modulated radiation therapy for prostate cancer.

PURPOSE: Quality of life (QoL) outcomes play a major role in the treatment selection for prostate cancer (CaP). We evaluated the urinary QoL outcomes in men who were treated with image-guided intensity-modulated radiation therapy (IG-IMRT) for CaP. METHODS AND MATERIALS: We enrolled men who were diagnosed with CaP and underwent IG-IMRT in a large urological group practice into a prospectively maintained database. The typical radiation treatment dosage to prostates and seminal vesicles was 8100 cGy in 45 fractions. Urinary QoL was self-assessed using the standardized incontinence grade and International Prostate Symptom Score (IPSS) at baseline and at each follow-up visit. We evaluated the cumulative incidence of urinary incontinence and changes in both continence and IPSS over time. RESULTS: Of the 3602 men who were eligible for analysis, 3086 (85.7%) had no urinary incontinence; 479 (13.3 %) had minimal incontinence (no requirement for pads), and 37 (1.0 %) had significant urinary incontinence that required the use of pads or interfered with activities of daily living, at baseline. After a median follow-up of 24 months (range: 12.0-41.0 months), these numbers were 80.6%, 17.4%, and 2.0%, respectively. Radiation therapy appeared to have a beneficial effect on some men: 54.1% of men with minimal incontinence became completely continent of urine during follow-up. Of those with significant urinary incontinence, 29.7% reported resolution and 27.0% reported improved symptoms with no requirement for pads. Of the 1276 men with moderate IPSS, the mean IPSS decreased from 12 to 9.8 at the time of the last follow-up (P < .001). Similarly, of the 233 men with severe IPSS, the mean IPSS decreased from 24 to 13 at the time of the last follow-up (P < .001). CONCLUSION: IG-IMRT for clinically localized CaP is associated with a relatively low incidence of urinary incontinence. Although unexplained, IG-IMRT seems to improve symptoms in some men with baseline urinary incontinence and moderate-to-severe IPSS.

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy.

PURPOSE: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. METHODS AND MATERIALS: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. RESULTS: Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. CONCLUSIONS: Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.