Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

PurposeMen with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT).Methods and MaterialsThree hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression.ResultsTen-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001).ConclusionsSurvival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.     

I-125 or Pd-103 for brachytherapy boost in men with high-risk prostate cancer: A comparison of survival and morbidity outcomes

PurposeBrachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy.Methods and MaterialsOf 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ² test with survival determined by the Kaplan–Meier method and Cox regression.ResultsMen treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150–200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes.ConclusionsBrachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival.     

Manual vs. automated implantation of seeds in prostate brachytherapy: Oncologic results from a single-center study

PurposeThe objective of this study was to study survival and tolerance of prostate cancer patients treated with ¹²⁵I permanent interstitial brachytherapy by automated vs. manual implantation of seeds.Methods and MaterialsBetween 2002 and 2010, 349 selected patients were treated with ¹²⁵I brachytherapy by the same team: from 2002 to April 2005, 65 patients with linked seeds and then 284 patients treated using Nucletron First System automated implantation. We analyzed biochemical recurrence-free survival (bRFS) rates and toxicities (univariate and multivariate analyses).ResultsTwo hundred seventy-seven (79.4%) and 69 patients (19.8%) with low- and intermediate-risk disease were treated, respectively (median follow-up: 64 months). The 5-year bRFS rate was 93.1% (95% confidence interval 89.3–95.6) for the entire cohort. The 5-year bRFS rates were 93.4% and 91.7% for patients with low- and intermediate-risk disease, respectively (p = 0.42). In univariate and multivariate analyses, there was no statistically significant difference in the 5-year bRFS rate depending on the implantation technique (93.1% vs. 91.8%, respectively, for automated and linked seeds; p = 0.53). In univariate analysis, only D₉₀ prostate (dose delivered to 90% of the prostate) <140 Gy (p = 0.01), lack of prostate-specific antigen bounce (p = 0.008), and nadir prostate-specific antigen >0.11 (p = 0.01) were predictive factors for bRFS. We observed Grade 3 urethritis in 7 patients (2%), urinary incontinence in 2 patients (0.7%), and Grade 4 proctitis in 2 patients (0.7%).ConclusionsIn this large single-center series, brachytherapy for selected localized prostate cancer achieved excellent rates of biochemical control at 5 years (93.1%) with an acceptable toxicity profile, irrespective of the implantation technique used.     

Risk factors for biochemical recurrence after a tissue-ablative prostate-specific antigen <0.2 ng/mL

PurposeA prostate-specific antigen (PSA) nadir <0.2 ng/mL is generally considered as tissue ablative and at low risk for recurrence. After attaining such a low PSA nadir, we analyzed risk factors for recurrence.Methods and materialsWe identified patients from our institutionalized database with either D'Amico low- or intermediate-risk prostate cancer that was treated with either low-dose-rate prostate brachytherapy or external beam radiotherapy as monotherapy. We compared patients who attained a nadir <0.2 ng/mL and subsequently developed biochemical failure to patients who did not experience biochemical failure by using χ² test and Student t test. Survival analysis was performed using the Kaplan–Meier method (log-rank test).ResultsOf 892 patients, 560 (63%) achieved a nadir <0.2 ng/mL. Only 23 (4.1%) later developed a biochemical recurrence. The 7-year Kaplan–Meier biochemical recurrence-free survival after a PSA nadir of <0.2 ng/mL was 96%. Patients who later experienced biochemical recurrence were more likely to have Cancer of the Prostate Risk Assessment Score intermediate- or high-risk cancer: (74% vs. 40%, p < 0.001). Patients were more likely to have a diagnostic PSA >6.0 ng/mL: (66% vs. 43% p < 0.001) and have a Gleason score ≥ 3  + 4: (52% vs. 34%, p = 0.005). They were also more likely to be older (p = 0.003): mean (SD) 70.3 (6.4) vs. 66.2 (6.5) and have a time to PSA nadir that was significantly shorter (p = 0.013): mean (SD) 51.8 (29.6) vs. 65.2 (25.1).ConclusionsBiochemical recurrence after attaining a PSA nadir <0.2 ng/mL is rare and more frequent in patients with intermediate risk cancer and older patients. These patients can benefit from a prolonged followup with specialized physicians.     

Development,implementation, and outcomes of a simulation-based medical education (SBME) prostate brachytherapy workshop for radiation oncology residents

PurposeDespite a preponderance of data demonstrating strong clinical outcomes and cost-effectiveness, prostate brachytherapy use and competency continue to decline. Enhanced resident education may help reverse this trend. We therefore developed and implemented a simulation-based medical education course for low-dose-rate prostate brachytherapy (LDR-PB).Materials and MethodsA 1-week LDR-PB course comprised four 1-h lectures on clinical outcomes, physics, radiobiology, and anatomy/contouring, followed by a 4.5-h simulation session on ultrasound-guided prostate phantom implantation, was developed for radiation oncology residents at an academic institution. A 10-statement Likert-scale survey and 20-question multiple-choice test were administered 1 week before and 4 weeks after the course.ResultsPrecourse and postcourse instruments were completed by 24 and 20 residents, respectively. The median number of prior LDR-PB cases after at least one genitourinary rotation was 10.5 (range 5–20). Overall mean test scores were significantly improved (55% before the course vs 68% after the course; p = 0.010). Mean Likert scores significantly increased on nine of 10 survey statements and were significantly increased overall (2.4 before the course vs 3.3 after the course, p < 0.001). When asked about interest in performing brachytherapy after residency, 37.5% of residents “agreed” or “strongly agreed” before the course vs 50% after the course (p = 0.41). Those with higher postresidency brachytherapy interest (scores of 4–5 vs 1–3) had significantly more LDR-PB cases (11.2 vs 5.3 cases; p = 0.005).ConclusionsA 1-week simulation-based medical education course for LDR-PB can improve didactic performance and self-reported technical competence/confidence, and may increase overall enthusiasm for brachytherapy. Future studies at our institution will incorporate evaluation of implant quality and assessment of procedural competence into this framework. Residency programs should dedicate resources to this essential component of radiation oncology.     

Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy

PurposeHydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration–approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy.MethodsEighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR.ResultsFifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V₈₀ < 0.005% vs. 0.010%, p = 0.003; V₇₅ < 0.005% vs. 0.14%, p < 0.0005; V₇₀ 0.09% vs. 0.88%, p < 0.0005; V₆₀ = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment.ConclusionsTransperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.     

Racial differences in the PSA bounce in predicting prostate cancer outcomes after brachytherapy: Evidence from the Department of Veterans Affairs

PurposeAfrican American men have historically had poorer prostate cancer biochemical and survival outcomes than Caucasians. However, emerging data suggest nononcologic factors drive much of this disparity. Prior evidence has suggested an association between a transient prostate specific antigen (PSA) bounce and improved biochemical control. However, racial differences in this relationship have remained relatively unexplored.Methods and MaterialsWe identified 4477 men treated for low- or intermediate-risk prostate cancer within the U.S. Department of Veterans Affairs (VA) from 2000 to 2010 with brachytherapy alone or in combination with external beam radiotherapy without androgen deprivation. Longitudinal PSA data were used to define to biochemical failure and PSA bounce. Cox proportional hazard models were used explore racial differences in the relationship between the PSA bounce and time to biochemical failure.ResultsThirty-one percent of our sample experienced a PSA bounce, with African Americans more likely to experience a bounce (42%) compared with Caucasians (29%); p < 0.001. Despite this, African Americans had a higher likelihood of biochemical failure (hazard ratio [HR] 1.4; p = 0.006). However, African American men experiencing a PSA bounce were less likely to experience a biochemical failure (HR = 0.64; p = 0.046), whereas this relationship was not statistically significant for Caucasians (HR = 0.78; p = 0.092). On multivariate analysis, African Americans receiving brachytherapy alone were most sensitive to the protective benefit of the PSA bounce (HR = 0.64).ConclusionsA PSA bounce was associated with improved biochemical control among patients receiving brachytherapy as part of their treatment for low- or intermediate-risk prostate cancer at the VA. African American men treated with brachytherapy had a particularly pronounced biochemical control benefit of a PSA bounce.     

Cesium-131 prostate brachytherapy: A single institutional long-term experience

AimsTo report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution.Materials and MethodsAll patients who underwent prostate brachytherapy with Cesium-131 (¹³¹Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD).ResultsEight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0–144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001.ConclusionsThe present study demonstrates that prostate brachytherapy with ¹³¹Cs achieves excellent long-term biochemical control.     

Comparison of prostate distortion by inflatable and rigid endorectal MRI coils in permanent prostate brachytherapy imaging

PurposeTo study the deformation of the prostate by a rigid reusable endorectal coil and a balloon-type endorectal coil (BTC) during MRI of the prostate in brachytherapy imaging.Methods and MaterialsThe prostate gland was contoured on 157 MRI scans from 52 prostate cancer patients undergoing brachytherapy. The curvature of the posterior prostate surface deformation was computed as a measure of prostate distortion and compared between scans with a BTC, rigid endorectal coil (REC), or no endorectal coil. For the nine patients who had MRIs with all three endorectal scenarios, a mean prostate deformation vector was also calculated between scenarios using deformable image registration. These measures of prostate distortion were compared with the prostate anterior-to-posterior to left-to-right ratio (AP/LR) on the largest prostate axial slice.ResultsSignificant differences in prostate curvature were found between scans without an endorectal coil versus a REC versus a BTC (p < 0.001). The mean prostate deformation was 3.9 mm due to the BTC and 2.0 mm for the REC (p = 0.012). The mean AP/LR ratio was 0.62 with a BTC versus 0.76 without a coil or 0.73 with a REC (p < 0.001), but no difference existed between scans with a REC versus no coil (p = 0.7). The AP/LR ratio showed moderate correlation with prostate curvature (r = 0.48), and with mean prostate deformation (r = −0.64 to 0.68).ConclusionsThe REC caused minimal deformation of the prostate compared with a BTC with adequate MR image quality, and calculation of the cross-sectional AP/LR ratio on the largest axial prostate slice can serve as a simple measure of prostate distortion.     

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial

PurposeTo compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).Methods and MaterialsAndrogen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL.ResultsCompared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).ConclusionsReplacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.     

Prebiopsy multiparametric MRI and PI-RADS version 2.0 for differentiating histologically benign prostate disease from prostate cancer in biopsies: A retrospective single-center comparison

PurposeTo investigate the diagnostic performance of Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2.0) for differentiating clinically significant prostate cancer (csPCa) from benign prostate disease on prebiopsy multiparametric MRI stratified by total prostate specific antigen (PSA) concentration.Materials and methods150 patients who had prebiopsy mpMRI, serum PSA concentration and subsequent biopsy were retrospectively analyzed. Patients were stratified by PSA concentration (Group1 ≥ 10 ng/mL; Group2 4.0–<10 ng/mL). MRI findings were assessed using PI-RADSv2.0 by two blinded radiologists. Lesions were graded histopathologically using the International Society of Urological Pathology (ISUP) score. Diagnostic performance of PI-RADSv2.0 was evaluated and compared to PSA and PSA Density (PSAD). The performance of the radiologists was compared including inter-observer agreement for PI-RADSv2.0. The correlation between imaging and histopathological biopsy results was analyzed.ResultsThe differences in total PSA, free/total PSA ratio and PSAD between benign (n = 78) and malignant (n = 72) groups were significant (p < 0.05). The PI-RADSv2.0 scores of the radiologists were strongly correlated (r = 0.912, p < 0.001) with excellent agreement, κ = 0.97 (95%CI: 0.90–1.03; p < 0.005). Receiver operating characteristics curve analysis showed significantly high predictive power for PI-RADSv2.0, total PSA and PSAD alone. Comparison of age, prostate volume, PSAD, free/total PSA ratio and total PSA values between ISUP1 and ISUP ≥ 2 cases revealed significantly increased PSAD (p < 0.001) and total PSA (p = 0.001) in the ISUP ≥ 2 group.ConclusionPI-RADSv2.0 had high diagnostic accuracy in both PSA groups. PI-RADSv2.0, PSAD and total PSA alone had significant high predictive power to detect csPCa. However, the combination of PI-RADSv2.0 and PSAD or total PSA for each reader showed no statistically significant improvement when compared to PI-RADSv2.0 alone.     

Early toxicity and health-related quality of life results of high-dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer

PurposeTo determine the acute toxicity and effect on health-related quality of life of a two-fraction regimen of high-dose-rate (HDR) prostate brachytherapy.Methods and materialsPatients with low- or intermediate-risk prostate cancer were treated with HDR brachytherapy as monotherapy in two implants of 13.5 Gy spaced 7–14 days apart. Patients completed International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) questionnaires at 1, 3, 6, 9, 12, 16, 20, and 24 months after brachytherapy. Proportion of patients in each IPSS category (mild = 0–7, moderate = 8–18, severe = 19+) was evaluated at each of the intervals above. Paired t tests with baseline values were done for IPSS and EPIC scores.ResultsThirty patients were accrued to the study. Median prostate-specific antigen was 8,7 (range 4.1–17.5). T stages were T1c = 65%, T2a = 21%, and T2b = 14%. Twenty-seven percent of patients had a Gleason score of 6 and 73% had a Gleason score of 7. IPSS categories at baseline, 1, 3, 6, 12, and 24 months were mild (81%, 43%, 58%, 62%, 76%, 64%), moderate (19%, 32%, 29%, 30%, 20%, 29%), and severe (0%, 25%, 13%, 7%, 4%, 6%), respectively. There was a significant decrease in EPIC sexual summary scores at 1, 3, 6, and 12 months of 0 points (p < 0.001), 17 points (p = 0.01), 18 points (p = 0.02), and 17 points (p = 0.01), respectively.ConclusionsThis is the first report of this cohort of patients treated with two-fraction HDR monotherapy. This regimen shows rates of toxicity and health-related quality of life that appear acceptable as compared to other treatment modalities. These results are also comparable with other reports with similar treatment regimens.     

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone

PurposeHigh-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution.MethodsBetween 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost (“3-D conformal radiotherapy [3DCRT] + HDR”; 215 patients) or 3DCRT alone (“3DCRT”; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures.ResultsThe 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037).ConclusionsHDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.     

Prostate-specific antigen bounce in patients treated before 60 years old by iodine 125 brachytherapy for prostate cancer is frequent and not a prognostic factor

PurposeThe only prognostic factor of prostate-specific antigen (PSA) bounce in prostate cancer found in several studies is young age but has never been specifically studied in this subset of patients for long-term results. Bounce characteristics, histological, clinical, and dosimetric data in young patients were analyzed, as well as their impact on toxicity and survival.Material and MethodsThis retrospective study included patients aged ≤60 years treated with exclusive iodine 125 brachytherapy with low or intermediary prostate adenocarcinoma during 1999–2014. Exclusion criteria were a follow-up of ≤24 months. PSA bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below.ResultsThis study analyzed 179 patients. Median age was 56 years (46–59 years). The median follow-up was 79 months (54; 123). The bounce incidence was 56.8% (49.6%; 64.2%) at 5 years, inversely proportional to positive/total biopsies ratio (HR 0.98, 95% CI [0.97, 0.99]). Incidence of biochemical failure was 1.2%, 95% CI (0.3%; 4.7%), at 5 years with no difference between the bounce and no-bounce group (HR 0.96, 95% CI [0.25; 3.58]). Bounce is an unfavorable prognostic factor for grade two and three urinary toxicities 6.67 (4.14; 10.76) (p < 0.001).ConclusionsPSA bounce is common in young people after brachytherapy. It should be monitored without starting an inadequate and sometimes invasive relapse checkup or a relapse treatment.     

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

PurposeTo validate the 2019 NCCN subgroups of favorable- and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification.MethodsWe included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis.ResultsOf 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3–214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00–4.10; p < 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78–5.50, p < 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6–6.1%) vs. 17.0% (95% CI, 13.6–20.5%; p < 0.001), and for distant metastasis were 1.6% (95% CI, 0.5–2.6%) vs. 5.4% (95% CI, 3.3–7.4%; p < 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54–3.36; p < 0.001) and 2–3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89–6.76; p < 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34–4.53, p = 0.004; 2–3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49–9.10, p < 0.001).ConclusionsThese findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.     

Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT

PurposeWe report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT.MethodsPatients received IMRT of 86.4 Gy (n = 470) or HDR brachytherapy (21 Gy in three fractions) followed by IMRT of 50.4 Gy (n = 160). Prostate-specific antigen (PSA) relapse was defined as PSA nadir + 2. Median followup was 53 months for IMRT alone and 47 months for HDR.ResultsThe 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p = 0.71), intermediate- (p < 0.001), and high-risk (p = 0.23) groups, respectively. Treatment (p = 0.0006), T stage (p < 0.0001), Gleason score (p < 0.0001), pretreatment PSA (p = 0.0037), risk group (p < 0.0001), and lack of androgen-deprivation therapy (p = 0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p = 0.0012, hazard ratio [HR] = 0.184); age (p = 0.0222, HR = 0.965); and risk group (p < 0.0001, HR = 2.683) were associated with improved PRFS on multivariate analysis.ConclusionDose escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the treatment of prostate cancer compared with ultra-high-dose IMRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients.     

Reducing seed migration to near zero with stranded-seed implants: Comparison of seed migration rates to the chest in 1000 permanent prostate brachytherapy patients undergoing implants with loose or stranded seeds

PurposePulmonary seed emboli to the chest may occur after permanent prostate brachytherapy (PPB). The purpose of this study is to analyze factors associated with seed migration to the chest in a large series of PPB patients from a single institution undergoing implant with either loose seeds (LS), mixed loose and stranded seeds (MS), or exclusively stranded seeds in an absorbable vicryl suture (VS).Methods and MaterialsBetween May 1998 and July 2015, a total of 1000 consecutive PPB patients with postoperative diagnostic chest x-rays at 4 months after implant were analyzed for seed migration. Patients were grouped based on seed implant technique: LS = 391 (39.1%), MS = 43 (4.3%), or VS = 566 (56.6%). Univariate and multivariate analysis were performed using Cox proportional hazards regression models to determine predictors of seed migration.ResultsOverall, 18.8% of patients experienced seed migration to the chest. The incidence of seed migration per patient was 45.5%, 11.6%, and 0.9% (p < 0.0001), for patients receiving LS, MS, or VS PPB, respectively. The right and left lower lobes were the most frequent sites of pulmonary seed migration. On multivariable analysis, planimetry volume (p = 0.0002; HR = 0.7 per 10 cc [0.6–0.8]), number of seeds implanted (p < 0.0001, HR = 2.4 per 25 seeds [1.7–3.4]), LS implant (p < 0.0001, HR = 15.9 [5.9–42.1]), and MS implant (p = 0.001, HR = 7.9 [2.3–28.1]) were associated with seed migration to the chest.ConclusionsIn this large series, significantly higher rates of seed migration to the chest are observed in implants using any LS with observed hazard ratios of 15.9 and 7.9 for LS and MS respectively, as compared with implants using solely stranded seeds.     

HDR brachytherapy as monotherapy for prostate cancer: A systematic review with meta-analysis

PurposeThe effectiveness and safety of high dose brachytherapy as monotherapy (HDR-BRT-M) in prostate cancer is limited to retrospective studies. We performed a meta-analysis to summarize existing data and identify trends in biochemical recurrence-free survival (bRFS) and toxicity after HDR-BRT-M in patients with prostate cancer.Methods and MaterialsRetrospective, prospective, or randomized clinical trials were identified on electronical databases through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-regression analysis was performed to assess if there is a relationship between moderator variables and bRFS. A p-value < 0.05 was considered significant.ResultsFourteen studies with a total of 3534 patients treated were included. The cumulative size of the bRFS at 5 years was 0.92 (95% confidence interval (CI) 0.48–0.61). The five-year bRFS for low, intermediate, and high risk was 97.5% (95% CI 96–98%), 93.5% (95% CI 91–96%), and 91% (95% CI 88–93%), respectively. The total biological effective dose (BED) (p = 0.02), the BED per fraction (p = 0.001), androgen deprivation therapy usage (p = 0.04), and the number of fractions of HDR-BRT-M (p = 0.024) were significantly associated with bRFS rate. The rate of late Grade 2/3 or > genitourinary and gastrointestinal toxicity was 22.4% (95% CI 9–35,2%)/1.4% (95% CI 0.8–2.1%) and 2.7% (95% CI 0–6.8%) and 0.2% (95% CI 0.1%–0.4%), respectively.ConclusionsHDR-BRT-M is safe with excellent rates of bRFS for all risk groups. The total BED, the BED per fraction, and number of fractions were the key factors associated with the biochemical control. These data can be useful to choose the size and number of BRT fractionation.     

Large prostate gland size is not a contraindication to low-dose-rate brachytherapy for prostate adenocarcinoma

PurposeProstate volume greater than 50 cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size.Methods and MaterialsA total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Mann–Whitney and Pearson's χ² tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes.ResultsPatient pretreatment factors were balanced between groups except for age (p = 0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p = 0.47). In a multivariate analysis, plan type (hazard ratio [HR] = 0.25, p = 0.03), dose to 90% of the gland (D₉₀: HR = 0.98, p = 0.02), volume receiving 200 Gy (V₂₀₀: HR = 0.98, p = 0.026), and biologic effective dose (HR = 0.99, p = 0.045), but not prostate size (HR = 2.27, p = 0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score.ConclusionIn men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size.