Search

Simple Summary: NCCN risk classifications for prostate cancer do not include elevated initial PSA levels as a single very-high-risk factor. However, an ultra-high initial PSA level (>50 ng/mL) showed a similar hazard ratio in the biochemical disease-free survival rate and the distant metastasis-free survival rate to the other single very-high-risk factors of T3b–4 and a Gleason score of 9–10. Therefore, an ultra-high initial PSA level has the potential to be a single very-high-risk factor for localized prostate cancer. To examine the impact of ultra-high iPSA levels of >50 ng/mL (uhPSA) after modern radiotherapy, we compared outcomes of 214 patients with uhPSA levels to 1161 other high-risk patients. Radiotherapy included brachytherapy ± external beam radiotherapy (EBRT) and EBRT alone (intensity-modulated radiotherapy or stereotactic body radiotherapy). The biochemical disease-free survival rate (bDFS), the distant metastasis-free survival rate (DMFS), local control, and pelvic lymph node control were analyzed. Patients with uhPSA levels had an inferior bDFS (84.8% at 5 years) and DMFS (93.9% at 5 years) compared to other high-risk patients (92.7% and 97.2%, both p < 0.001). The uhPSA group showed more distant metastases than the non-uhPSA group; however, the frequencies of local failure and pelvic lymph node recurrence were similar. The uhPSA group demonstrated hazard ratios (HRs) of 2.74 for bDFS and 2.71 for DMFS, similar to those of T3b–4 (HR 2.805 and 2.678 for bDFS and DMFS) and GS 9–10 (HR 2.280 and 2.743 for bDFS and DMFS). An uhPSA level could be a candidate for a single VHR factor to identify high-risk patients who require intensified treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In general, brachytherapy (BT) improves biochemical control in intermediate-to high-risk prostate cancer. We previously reported that importance of very high-risk factors (VHR: T3b–4 or Gleason score 9–10) and patients with double VHR (VHR-2) showed the worst prognosis among high-risk groups. We explored the role of BT-boost in patients with VHR and compared it to intermediate- and other high-risk groups. We confirmed that BT-boost improved prostate-specific antigen (PSA) control but resulted in equivalent overall survival rates for the intermediate- and high-risk groups, except for the patients with VHR. In the VHR-1 group (single VHR), BT-boost showed superior PSA control to conventional-dose RT (EQD2 ≤ 72 Gy) but not to the dose-escalated radiotherapy group (EQD2 ≥ 74 Gy). In the VHR-2 group, BT-boost did not improve the biochemical control rate of either Conv RT or DeRT. BT-boost showed no benefit over modern DeRT in the patients with VHR. This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b–4 or Gleason score 9–10) as patients with double very high-risk factors (VHR-2: T3b–4 and Gleason score 9–10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments. [ABSTRACT FROM AUTHOR]

To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093–1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774–7.383, p < 0.001) than in BT ± EBRT (1.1%). In detailed subgroup analyses, the high-dose UHF group (H-UHF) using BED ≥ 226 Gy1.5, showed higher GI toxicity profiles than the other subgroups (HDR + EBRT, LDR + EBRT, and LDR monotherapy, and L-UHF BED < 226 Gy1.5) with equivalent GU toxicity to other modalities. With a median follow-up period of 32 months and 75 months, the actuarial biochemical control rates were equivalent between the UHF and BT ± EBRT groups. UHF showed equivalent efficacy, higher GI and equivalent GU accumulated toxicity to BT ± EBRT, and the toxicity of UHF was largely dependent on the UHF schedule. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer. We compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions). The actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217). The 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity. [ABSTRACT FROM AUTHOR]

Highlights • A long-term data for HDR-BT monotherapy and LDR-BT with or without EBRT. • LDR-BT showed equivalent PSA control and late toxicity ≥G2 GI and GU with HDR-BT. • LDR-BT showed higher acute ≥G2 GU and late grade 1 GU toxicity. • Acute GU toxicity predict late GU toxicity grade ≥G2. • Additional EBRT with LDR-BT elevated GI toxicity to LDR-BT only. Abstract Background To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy (EBRT) for localized prostate cancer. Methods and materials We compared 352 patients treated with HDR-BT as monotherapy (median follow-up time 84 months, NCCN risk classification; low: intermediate: high = 28:145:179) and 486 patients with LDR-BT with or without EBRT (90 months, 194:254:38). HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. LDR-BT excluded patients with T3b–T4 tumor and initial PSA >50 ng/ml. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Results The actuarial 5-year biochemical failure-free survival rates (bNED) were 92.9% and 95.6% (p = 0.25) in the HDR-BT and LDR-BT groups, respectively, and it was 100% and 97.3% (p = 0.99) in the low-risk, 95.6% and 94.3% (p = 0.19) in the intermediate, 89.6% and 94.9% (p = 0.26) in the high-risk groups, and 93.1% and 94.9% (p = 0.98) in selected high-risk group excluding T3b-4 and initial PSA ≥50. IPTW correction also indicated no difference in bNED between LDR-BT and HDR-BT groups. LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade ≥2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Acute GU toxicity grade ≥1 predicted late GU toxicity grade ≥2. External beam radiotherapy plus LDR-BT elevated GI toxicity than LDR-BT only group. Accumulated incidence of late grade ≥2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. No grade 4 or 5 toxicities were detected in either modality. Conclusion HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT with or without EBRT for low-, intermediate- and selected high-risk patients. LDR-BT showed equivalent incidence of grade ≥2 late GI and GU toxicities and higher grade ≥2 acute GU toxicity as that of HDR-BT as a monotherapy. [ABSTRACT FROM AUTHOR]

Highlights • A long-term retrospective data for three frequently used HDR-BT monotherapy schedules. • All HDR-BT monotherapy schedules showed excellent outcome in biochemical control. • Higher BED correlated with higher but acceptable genitourinary toxicity. Abstract Background Herein, we report the outcomes of 3 schedules of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy for localized prostate cancer. Patients and methods A total of 347 patients were treated with 45.5 Gy/7 fractions (n = 86; 45.5 Gy arm, median follow-up time 131 months), 49 Gy/7 fractions (n = 149; 49 Gy arm, 75.9 months), and 54 Gy/9 fractions (n = 112; 54 Gy arm, 68 months). Results The actuarial 5-year biochemical failure-free survival rates were 86.8%, 94.1%, and 88.5% (p = 0.2023) for the 45.5 Gy, 49 Gy, and 54 Gy arms in the high-risk group; 90.4%, 100%, and 97.4% (p = 0.0818) in the intermediate-risk group; and not available, 100%, and 100% in the low-risk group, respectively. The 5-year distant metastasis-free (and overall) survival rates were 94.4%, 98.2%, and 96.3% (100%, 92.8%, and 99.1%) for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5454 and p = 0.0028), respectively. At 5 years, accumulated incidence of grade ≥2 gastrointestinal toxicity was 1.2%, 2.7%, and 3.4% for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5605), respectively. For genitourinary toxicity, the 49 Gy arm showed a higher grade ≥2 toxicity of 20.5% than those observed in the 45.5 Gy (2.4%) and 54 Gy arms (10.1%). No grade 4 or 5 of either type of toxicity was detected. Conclusions The 3 schedules showed equivocal outcomes in each risk group, with different toxicity profiles. HDR-BT monotherapy with these schedules is an acceptable treatment option for localized prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, shortening treatment time is becoming more important. Ultrahypofractionated radiotherapy (UHF) for localized prostate cancer is a fascinating treatment strategy; however, the concept of a well-balanced, optimal dose during UHF radiotherapy remains a contentious strategy, with only a few studies on UHF already reported. We must wait for the results of randomized trials several years away. Therefore, we tried to reveal the acceptable schedule in comparison to conventional to moderate hypofractionated radiotherapy so far. We found that UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy. The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients treated with DeRT using multi-institutional retrospective data. To analyze toxicity, we divided UHF into High-dose UHF (H-UHF; equivalent doses of 2 Gy per fraction: EQD2 > 100 Gy1.5) and low-dose UHF (L-UHF; EQD2 ≤ 100 Gy1.5). In toxicity, H-UHF elevated for 3 years accumulated late gastrointestinal and genitourinary toxicity grade ≥ 2 (11.1% and 9.3%) more than L-UHF (3% and 1.2%) and DeRT (3.1% and 4.8%, p = 0.00126 and p = 0.00549). With median follow-up periods of 32.0 and 61.7 months, the actuarial 3-year biochemical failure-free survival rates were 100% (100% and 100% in the L-UHF and H-UHF) and 96.3% in the low-risk group, 96.5% (97.1% and 95.6%) and 94.9% in the intermediate-risk group, and 93.7% (100% and 94.6%) and 91.7% in the high-risk group in the UHF and DeRT groups, respectively. UHF showed equivocal efficacy, although not conclusive but suggestive due to a short follow-up period of UHF. L-UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, high-risk prostate cancer was subdivided to a very-high-risk group considered to have the worst prognosis, including clinical stage T3b–T4, primary Gleason pattern 5, or more than four biopsy cores with Gleason score 8–10. Among these, T3b–T4 stage is a special interest in radiotherapy because of their wider target volume outside the prostate. We examined this subgroup and found that dose escalation in radiotherapy both with brachytherapy or intensity modulated radiotherapy (IMRT) improved biochemical free survival rate but not in prostate cancer specific survival rate and overall survival rate. To examine the efficacy of dose escalating radiotherapy into patients with cT3b or T4 localized prostate cancer, we compared Group A (86 conventional dose external beam radiotherapy: EBRT group, treated with 70–72 Gy) and group B (39 high dose EBRT group (HDEBRT group, 74–80 Gy) and 124 high-dose-rate brachytherapy (HDR) + EBRT (HDR boost)) using multi-institutional retrospective data. The actuarial 5-year biochemical disease-free survival (bDFS) rate, prostate cancer specific survival rate (PSS), and overall survival rate (OS) were 75.8%, 96.8%, and 93.5%. Group B showed superior 5-year bDFS rate (81.2%) as compared to the group A (66.5%) (p < 0.0001) with a hazard ratio of 0.397. Equivocal 5-year PSS (98.3% and 94.8% in group B and group A) and OS (both 93.7%) were found between those groups. Accumulated late grade ≥ 2 toxicities in gastrointestinal and genitourinary tracts were similar among those three groups. Therefore, both HDEBRT and HDR boost could be good options for improving the bDFS rate in cT3–T4 localized prostate cancer without affecting PSS and OS. [ABSTRACT FROM AUTHOR]

The aim of this paper is to compare outcomes between high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer. We examined 353 HDR-BT and 270 IG-IMRT patients. To reduce background selection bias, we used the method of inverse probability treatment weighting (IPTW) with propensity scores. The actuarial five-year biochemical failure-free survival rates were 92.9% and 96.7% (p = 0.1847; p = 0.077 in IPTW) for HDR-BT and IG-IMRT, respectively; they were 100% and 95.8% (p = 0.286) for the low-risk group, 95.6% and 92% (p = 0.42) for the intermediate-risk group, 90.4% and 84.9% (p = 0.1059; p = 0.04 in IPTW) for the high-risk group, and 87.1% and 89.2% (p = 0.3816) for the very-high-risk group. In the assessment of accumulated incidences of grade ≥ 2 toxicity (Common Terminology Criteria for Adverse Events version 4.0) at five years, HDR-BT monotherapy showed higher genitourinary toxicity (11.9%) than IG-IMRT (3.3%) (p < 0.0001). The gastrointestinal toxicity was equivalent for HDR-BT (2.3%) and IG-IMRT (5.5%) (p = 0.063). No Grade 4 or 5 toxicity was detected in either modality. HDR-BT showed higher genitourinary toxicity than IG-IMRT. HDR-BT and IG-IMRT showed equivalent outcomes in low-, intermediate-, and very-high-risk groups. For high-risk patients, HDR-BT showed potential to improve prostate-specific antigen (PSA) control rate compared to IG-IMRT. [ABSTRACT FROM AUTHOR]