Biochemical Disease-free Survival Rates Research Articles

Ultra-High Prostate-Specific Antigen Level: A Potential Very-High-Risk Factor for Localized High-Risk 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.

Focal Cryoablation of the Prostate: Primary Treatment in 163 Patients With Localized Prostate Cancer.

Objective Whole gland treatment of the prostate has known efficacy in treating many grades of prostate cancer. However, it is often associated with increased morbidity, including erectile dysfunction and urinary incontinence. Focal ablative therapies, including focal cryoablation (FC), are utilized to minimize the risk of tumor progression and preserve erectile and urinary function. There is little to no consensus on whether intermediate or high-risk prostate cancer should be treated with focal therapy. However, there is a growing body of literature on the effectiveness of FC as an effective means of prostate cancer control. We characterize our experience with 163 patients who underwent FC with a median follow-up of 39 months (IQR: 24-60). Methods A 163-patient retrospective cohort underwent FC of the prostate at a single clinic by a physician from November 2008 to December 2020. Each of these T1c patients in this single-tail study was monitored for biochemical recurrence (BCR) and oncologic outcomes. American Society for Radiation Oncology (ASTRO) definition of BCR is three consecutive prostate-specific antigens (PSA) increases of more than 0.5 ng/mL or, along with the utilization of the Phoenix definition, a PSA greater than nadir by 2 ng/mL was used to define BCR. This study's primary endpoint includes BCR or biochemical disease-free survival rates. Secondary endpoints include patient side effects, such as measuring for urinary incontinence and outcomes of salvage treatments. Cox proportional hazard analyses defined univariate HRs and 95% CIs for pre-operative PSA (POPSA), Decipher, and Gleason Grade Groups (GGGs) to determine the prognostic impact of pathologic factors. Statistical analysis and BCR timeline analysis also included logistic regression and the Kaplan-Meier method, with significance considered at p < 0.05. Select focal cryotherapy patients were monitored utilizing genomic sequencing tests. Results Our cohort included 27 patients (16.5%) with D'Amico low, 115 patients (70.5%) with intermediate, and 23 patients (14.1%) with high-risk prostate cancers. One month after FC, a 73% reduction in PSA resulted in a median post-operative PSA of 1.39 ng/mL (IQR: 0.46-2.80 ng/mL). At five years, our cohort yielded biochemical disease-free recurrence rates of 78%, 74%, and 55% for low, intermediate, and high-grade cancers, respectively. Genetic risk stratification results showed very similar BCR rates to patients whose tissues did not undergo genomic testing, at 27%, 26%, and 46% for low, intermediate, and high-grade cancers, respectively. Log-rank tests to map for BCR and HRs for pathologic factors did not yield any statistically significant predictive results. Urinary incontinence and erectile dysfunction were reported in 1.8% and 3.1% of patients in the focal cohort. Conclusions Our results add to the expanding body of literature around the efficacy of focal ablative therapies in contrast to whole gland treatment. The definitive extent of FC's efficacy still remains to be explored, but our conclusions demonstrate favorable PSA kinetics at five years follow-up.

Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9\u201310 clinical localized prostate cancer

As several recent researches focus on the importance of Gleason 9–10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9–10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9–10 prostate cancer.

Novel Prognostic Index of High-Risk Prostate Cancer Using Simple Summation of Very High-Risk Factors.

Simple SummaryWe explored the role of each very high-risk factor and found that simple summation of the number of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) is an easy and very high predictive power to separate VHR-2 (both T3b–4 and Gleason score 9–10) and others (VHR-1; T3b–4 or Gleason score 9–10, VHR-0; none of T3b–4 and Gleason score 9–10). The VHR-2 group showed a strikingly lower biochemical control rate and distant metastasis free survival rate than other groups, resulting in higher prostate cancer specific mortality than the VHR-1 and VHR-0 groups.This study aimed to examine the role of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors—VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF.

Radiotherapy for Clinically Localized T3b or T4 Very-High-Risk Prostate Cancer-Role of Dose Escalation Using High-Dose-Rate Brachytherapy Boost or High Dose Intensity Modulated Radiotherapy

Simple SummaryRecently, 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.

Analysis of oncological outcomes of whole-gland therapy with high-intensity focused ultrasound for localized prostate cancer in clinical and technical aspects: a retrospective consecutive case-series analysis with a median 5-year follow-up

Purpose This study aimed to analyze technical and clinical factors related to oncological outcomes in patients with localized prostate cancer (PC) who were treated with whole-gland high-intensity focused ultrasound (HIFU). Materials and Methods From 2007–2014, patients diagnosed with localized PC who underwent whole-gland HIFU were consecutively included retrospectively. Biochemical failure was defined according to the Phoenix ASTRO guidelines. The relationship between oncological outcomes and technical and clinical factors was evaluated. Results The study cohort included 428 patients. The median age was 67 years, and the median prostate-specific antigen level was 7.61 ng/mL. Patient risk classifications were low (n = 102), intermediate (n = 240), and high (n = 86). Biochemical disease-free survival rates of patients with HIFU for localized PC in the total, low-, intermediate-, and high-risk groups according to D’Amico risk groups over a median follow-up period of 5 years (range 9-144) were 68.4%, 80.4%, 65.6%, and 61.6%, respectively. In multivariate logistic regression analyses to predict biochemical failure of the treatment, neoadjuvant hormonal therapy (NHT) in the high-risk group (OR 0.225, p = 0.015), and compression method in the low- (OR 0.178, p = 0.030), intermediate- (OR0.291, p < 0.0001), and high-risk (OR 0.316, p = 0.049) groups were significant factors that reduced the risk of biochemical failure after treatment. There were no significant differences in complications between patients treated with compression and those treated conventionally. Conclusions NHT may potentially improve oncological outcomes for patients in the high-risk group, and compression methods can improve the oncological outcomes of whole-gland therapy with HIFU.

A systematic review of salvage focal therapies for localised non-metastatic radiorecurrent prostate cancer.

Although radiotherapy to the prostate for cancer is effective, recurrence occurs in 10–15% within 5 years. Traditional salvage treatments for men with radiorecurrent prostate cancer comprise of watchful waiting (WW) with or without androgen deprivation therapy (ADT) or radical prostatectomy (RP). Neither strategy provides ideal therapeutic ratios. Salvage focal ablation is an emerging option. We performed a systematic review of the Medline and Embase databases for studies reporting outcomes of focal salvage brachytherapy (sBT), cryotherapy (sCT) or high-intensity focused ultrasound (sHIFU) for radiorecurrent prostate cancer (conception to April 2019). Results were screened for inclusion against predetermined eligibility criteria. Certain data were extracted, including rates of biochemical disease-free survival (BDFS), metastasis, conversion to second-line therapies and adverse events. Of a total 134 articles returned from the search, 15 studies (14 case series and 1 comparative study) reported outcomes after focal sBT [5], sCT [7] and sHIFU [3]. Cohort size varied depending on intervention, with eligible studies of sBT being small case series. Median follow-up ranged from 10 to 56 months. Although pre-salvage demographics were similar [median age range, 61–75 years; prostate-specific antigen (PSA) range, 2.8–5.5 ng/mL], there was heterogeneity in patient selection, individual treatment protocols and outcome reporting. At 3 years, BDFS ranged from 61% to 71.4% after sBT, 48.1–72.4% after sCT and 48% after sHIFU. Only studies of sCT reported 5-year BDFS, which ranged from 46.5% to 54.4%. Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies (although this was poorly reported). Grade 3 adverse events were rare. This systematic review indicates that salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated. Unfortunately, there is heterogeneity in the study design of existing evidence. Level 1 research comparing salvage focal therapies to existing whole-gland strategies is needed to further establish the role of these promising treatments.

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PurposeLiterature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. Materials and methodsA total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. ResultsLate genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. ConclusionDespite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.

Linac-based stereotactic body radiation therapy vs moderate hypofractionated radiotherapy in prostate cancer: propensity-score based comparison of outcome and toxicity.

Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT). We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates. 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029). Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT. Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one.

Favorable 10-year outcomes of image-guided intensity-modulated radiotherapy combined with long-term androgen deprivation for Japanese patients with nonmetastatic prostate cancer.

To investigate 10-year outcomes of high-dose image-guided intensity-modulated radiation therapy (IG-IMRT) combined with long-term androgen deprivation therapy (ADT) for Japanese patients with nonmetastatic prostate cancer. A retrospective analysis was performed on 208 Japanese patients with T1-4N0M0 prostate cancer, who underwent definitive IG-IMRT from 2006 to 2010 at our single institution. The median dose was 78Gy (74-78) and median ADT time was 32 months (6-151). The risk stratification followed the National Comprehensive Cancer Network criteria. A biochemical relapse was defined as nadir plus 2.0ng/mL. Toxicity was scored with the Radiation Therapy Oncology Group morbidity scale. The median follow-up time was 102 months. For low-, intermediate-, high-, and very-high-risk groups, the 10-year biochemical disease-free survival rates were 100%, 84%, 90%, and 72%, respectively (P=0.008); clinical relapse-free survival rates were 100%, 100%, 100%, and 81%, respectively (P<0.001); and cancer-specific survival rates were 100%, 100%, 100%, and 89%, respectively (P=0.13). The independent prognostic factors influencing biochemical relapse were younger age, Gleason score ≥ 8, and radiation dose<78Gy in the multivariate analysis (P=0.006, 0.014, and 0.013). The 10-year cumulative incidence of late grade 2 or higher gastrointestinal and genitourinary toxicities were 12% and 13%, respectively. No events of grade 4 or 5 were observed. This study suggest that high-dose IG-IMRT combined with long-term ADT is effective and implementable, leading to excellent 10-year outcomes for Japanese patients with nonmetastatic prostate cancer.

Oligorecurrent Nodal Prostate Cancer: Long-term Results of an Elective Nodal Irradiation Approach.

The objective of this study was to report long-term results of elective nodal radiotherapy (ENRT) in prostate cancer (PCa) patients with oligorecurrent nodal disease after primary treatment. Data of 53 oligorecurrent PCa patients (N1 and/or M1a) with ≤5 nodal metastases (n=108) treated with ENRT combined with androgen deprivation therapy (ADT) between 2004 and 2016 were retrospectively reviewed. Median prostate-specific antigen (PSA) and PSA doubling time (DT) were 3.4 ng/mL and 5 months, respectively. At restaging, 45% of the patients presented single nodal metastases, mainly located in the pelvis (n=38). All patients underwent ENRT between 45 and 50.4 Gy with a boost on positive nodes (median 64.4 Gy; 54 to 69 Gy) using mainly VMAT (n=24) or IMRT (n=21) techniques. Concomitant ADT was administered to all patients for a median time of 6 months. After a median follow-up after ENRT of 44 months (range, 2 to 133), the 5-year biochemical disease-free and distant progression-free survival (DPFS) rates were 43% and 58%, respectively, with worse DPFS observed in patients with a PSA-doubling time <3 months (36.8% vs. 63.6%; P=0.029). Seventeen of 19 clinically relapsing patients presented lesions out of the ENRT field, and 10 were again oligometastatic. Only 2 patients presented with a CTCAE v3.0 grade ≥2 genitourinary toxicity. ENRT combined with short-course ADT is a safe and effective salvage modality for patients with oligorecurrent nodal PCa. Prospective randomized studies comparing focal SBRT versus ENRT are warranted to define the best treatment strategy.

Robot-asssisted laparoscopic radical prostatectomy (ralp). Oncological and functional findings after 90 cases

The RALP is the most modern technology available for the treatment of intracapsular prostate cancer (CaP), which can produce a shorter learning curve and better results than the traditional techniques. METHODS. Between March 2005 and March 2008, 90 patients (64.3 ys, range 52-71) with intracapsular CaP underwent RALP at our institute. Before surgery the patients underwent routine examinations and filled in IIEF, IPSS and EORTC-QLQC30/PR 25 questionnaires. Patients were followed up with PSA assay, physical examination and compilation of the questionnaires. Median follow-up was 12.5 months (range 1-35 months). RESULTS. Mean operative time was 230 min. Discharge and catheter removal were at day 7.4 and 8.2, respectively, after surgery. Pathological staging reported pT2 and pT3 in 57 (63%) and 33 patients (37%), respectively. Positive surgical margins were assessed in 30 patients (33%), particularly 8.7% in pT2 tumors. The one-year biochemical disease-free survival rate was 90%. Regarding the functional results, 81 patients (90%) were perfectly continent while a mild and a moderate incontinence were reported in 7 (8%) and 2 (2%) patients, respectively. Mean IPSS score decreased from 8 to 4; among the patients who underwent bilateral nerve sparing RALP and no adjuvant therapy, 31 (70.4%) reported satisfactory sexual intercourses. Concerning postoperative quality of life, mean EORTC-QLQC30/PR 25 questionnaires scores were very similar before and after RALP. CONCLUSIONS. After 90 cases of RALP the oncological and functional results are definitely promising. However, a wider number of patients and a greater follow-up are needed to confirm these data particularly as regards the functional results.

Clinical outcome and toxicity evaluation of simultaneous integrated boost pelvic IMRT/VMAT at different dose levels combined with androgen deprivation therapy in prostate cancer patients.

BackgroundThe role of dose escalation in patients receiving long-term androgen deprivation therapy (ADT) is still a controversial issue. The aim of the current study was to evaluate whether dose escalation for ≥76–80 Gy had any advantage in terms of biochemical disease-free survival (BDFS), distant metastasis-free survival (DMFS), or overall survival outcomes over the dose levels from 70 to <76 Gy.Patients and methodsThe study included a cohort of 24 patients classified with high- and intermediate-risk localized prostate cancer. All patients received ADT, starting at 4–6 months before radiation therapy and continued for a total period of 12–24 months in high-risk patients. The treatment plan was given in two phases. In the first phase, the nodal planning target volume (PTV) and the prostate PTV received 48.6 and 54 Gy, respectively, over 27 fractions. The treatment was applied through intensity-modulated radiation therapy or volumetric modulated arc therapy with a simultaneous integrated boost technique.ResultsMore than half of the patients were in T3–T4 stage, 79.1% of the patients were in the high-risk category, and all patients received ADT. The rate of acute grade II gastrointestinal and genitourinary toxicities in all patients were 41.7% and 62.5%, respectively. The rate of freedom from grade II rectal toxicity at 2 years was 89% and 83% for patients treated with dose levels <76 and ≥76 Gy, respectively. The rate of BDFS at 2 years was 90% and 85% for doses <76 and ≥76 Gy, respectively. The DMFS at 2 years was 100% and 76% for dose levels <76 and ≥76 Gy, respectively.ConclusionIn the current study, there were no significant differences in the BDFS and DMFS between patients treated with a dose of <76 and ≥76 Gy, including elective pelvic lymph nodes irradiation combined with ADT.

Association de radiothérapie externe et de curiethérapie pour les cancers de la prostate

Brachytherapy as sole treatment is standard of care for D’Amico classification low-risk prostate cancer. For intermediate and high-risk patients, brachytherapy can be associated to external beam radiation therapy to better take into account the risk of extracapsular effraction and/or seminal vesicle involvement. Three randomized studies have shown that this association increases freedom from relapse survival compared to exclusive external beam radiation therapy. This benefit is not shown for overall survival. The addition of a hormonal therapy to this association is most likely mandatory for high-risk patients, and needs to be confirmed for intermediate risk patients. Both high-dose rate and low-dose rate brachytherapy are suitable with similar biochemical disease free survival rates. High-dose rate brachytherapy seems to have a better genitourinary tolerance profile, while low-dose rate brachytherapy is an easier process and has a more widespread expertise.

Focal salvage high-intensity focused ultrasound in radiorecurrent prostate cancer.

To assess short- to medium-term cancer control rates and side effects of focal salvage high- intensity focused ultrasound (HIFU). A retrospective registry analysis identified 150 men who underwent focal salvage HIFU (FS-HIFU) (Sonablate 500) between November 2006 and August 2015. Metastatic disease was excluded by nodal assessment on the pelvic MRI, a radioisotope bone scan and positron-emission tomography (PET) imaging (choline-18F-fluorodeoxyglucose PET or choline PET-CT). In our current clinical practice, metastatic disease must be excluded by both choline PET and bone scan. Localization of cancer was carried out using multiparametric MRI of the prostate (T2-weighted, diffusion-weighted and dynamic contrast-enhanced imaging) with systematic or template prostate mapping biopsies. The primary outcome was a composite failure incorporating biochemical failure (BCF) and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. The secondary outcome was BCF using the Phoenix-ASTRO definition (prostate-specific antigen [PSA] nadir + 2ng/mL). We used Kaplan-Meier analysis and Cox proportional hazards regression to quantify the effect of the determinants on the endpoints. The mean (standard deviation [sd]) patient age at focal salvage HIFU was 69.8 (6.1) years and the median (interquartile range [IQR]) PSA pre-focal salvage HIFU was 5.5 (3.6-7.9) ng/mL. The median (IQR) follow-up was 35 (22-52) months. Patients were classified as having low- 2.7% (4/150), intermediate- 39.3% (59/150) and high-risk disease 41.3% (62/150) according to D'Amico classification, prior to focal salvage HIFU. Composite failure occurred in 61% of patients (91/150) and BCF occurred in 51.3% (77/150). The Kaplan-Meier composite endpoint-free survival (CEFS) rate at 3years was 40% (95% confidence interval [CI] 31-50) for the entire group. Kaplan-Meier estimates of CEFS were 100%, 49% and 24% at 3years in the low-, intermediate- and high-risk groups pre-salvage HIFU, respectively. The Kaplan-Meier biochemical disease-free survival (BDFS) rate at 3years was 48% (95% CI 39-59) for the entire group. Kaplan-Meier estimates of BDFS were 100%, 61% and 32% at 3years in the low-, intermediate- and high-risk groups pre-salvage HIFU, respectively. Complications included urinary tract infection (11.3%; 17/150), bladder neck stricture (8%; 12/150), recto-urethral fistula after one HIFU procedure (2%; 3/150) and osteitis pubis (0.7%; 1/150). Focal salvage HIFU conferred a relatively low complication and side effect rate. CEFS and biochemical control in the short to medium term were reasonable, especially in this relatively high-risk cohort, but still low compared with current whole-gland salvage therapies. Focal salvage therapy may offer disease control in men at high risk whilst minimizing additional treatment morbidities.

Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy: a comprehensive review

Background/AimPatients with locally recurrent prostate cancer after primary radiotherapy can be eligible for salvage treatment. Whole-gland salvage techniques carry a high risk of toxicity. A focal salvage approach might reduce the risk of adverse events while maintaining cancer control in carefully selected patients. The aim of this review was to evaluate current literature to assess whether focal salvage leads to a comparable or favourable recurrence rate and less toxicity compared to whole-gland salvage.MethodsA literature search was performed using PubMed, Embase and the Cochrane Library. A total of 3015 articles were screened and assessed for quality. Eight papers [on focal cryoablation (n = 3), brachytherapy (n = 3) and high-intensity focused ultrasound (n = 2)] were used to report outcomes.ResultsOne-, 2-, 3- and 5-year biochemical disease-free survival (BDFS) ranges for focal salvage are, respectively, 69–100, 49–100, 50–91 and 46.5–54.5 %. Severe genitourinary, gastrointestinal and sexual function toxicity rates are 0–33.3 %. One study directly compares focal to whole-gland salvage cryotherapy, showing 5-year BDFS of, respectively, 54.4 and 86.5 % with lower toxicity rates for focal salvage patients.ConclusionProvisional data suggest that BDFS rates of focal salvage are in line with those of whole-gland approaches. There is evidence that focal salvage could decrease severe toxicity and preserve erectile function.Electronic supplementary materialThe online version of this article (doi:10.1007/s00345-016-1811-9) contains supplementary material, which is available to authorized users.

A retrospective analysis after low-dose-rate prostate brachytherapy with permanent (125)I seed implant: clinical and dosimetric results in 70 patients.

To evaluate the biochemical disease-free survival (bDFS) rate after (125)I permanent-implant prostate brachytherapy. Patients with a diagnosis of prostate adenocarcinoma and adequate PSA follow-up were selected for this retrospective study. Brachytherapy with permanent (125)I seeds was performed as monotherapy, with a prescribed dose of 145 Gy to the prostate. Patients were stratified into recurrence risk groups according to the National Comprehensive Cancer Network (NCCN) guidelines. Biochemical failure was defined using the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. The post-implant D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient. Two cutoff points were used to test the correlation between D90 and bDFS results: 130 Gy and 140 Gy. bDFS was calculated from the implant date to the date of biochemical recurrence. Univariate and multivariate analysis were performed using the SPSS software and included clinical stage, pretreatment PSA, Gleason score (GS), androgen deprivation therapy, D90, and risk groups. In the univariate analysis we used a cutoff point of 5.89 ng/mL for PSA and 5 for GS. From June 2003 to April 2007, 70 patients were analyzed. The patients' distribution into recurrence risk groups was as follows: 39 patients (56%) in the low-risk group, 23 patients (33%) in the intermediate-risk group, and 8 patients (11%) in the high-risk group. At a median follow-up of 47 months (range, 19-70 months) bDFS was 88.4%, with a global actuarial 5-year bDFS of 86%. Disease-related factors including initial PSA level, GS and risk group were significant predictors of biochemical failure ( P = 0.01, P = 0.01, P = 0.006, respectively). In multivariate analysis, risk group (P = 0.005) and GS (P = 0.03) were statistically significant. Our data are in agreement with those in the literature and, despite the short follow-up, confirm the advantage of brachytherapy for patients at low and intermediate risk of recurrence.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

BackgroundBoth dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT.FindingsIn our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome.ConclusionThere was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

Focal partial salvage low-dose-rate brachytherapy for local recurrent prostate cancer after permanent prostate brachytherapy with a review of the literature.

PurposeTo investigate the treatment results for focal partial salvage re-implantation against local recurrence after permanent prostate brachytherapy.Material and methodsBetween January 2010 and September 2015, 12 patients were treated with focal partial salvage re-implantation for local recurrence after low-dose-rate brachytherapy using 125I seeds. The focal clinical target volume (F-CTV) was delineated on positive biopsy areas in a mapping biopsy, combining the cold spots on the post-implant dosimetry for initial brachytherapy. The F-CTV was expanded by 3 mm to create the planning target volume (PTV) as a margin to compensate for uncertainties in image registration and treatment delivery. The prescribed dose to the PTV was 145 Gy. The characteristics and biochemical disease-free survival (BdFS) rates were analyzed. Genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.ResultsThe median prostate-specific antigen (PSA) level at re-implantation was 4.09 ng/ml (range: 2.91-8.24 ng/ml). The median follow-up time was 56 months (range: 6-74 months). The median RD2cc and UD10 were 63 Gy and 159 Gy, respectively. The 4-year BdFS rate was 78%, which included non-responders. Biochemical recurrence occurred in two patients after 7 and 31 months, respectively. The former was treated with hormonal therapy after biochemical failure, and the latter underwent watchful waiting (PSA at the last follow-up of 53 months: 7.3 ng/ml) at the patient's request. No patients had grade 3 GU/GI toxicities or died after salvage re-implantation.ConclusionsThe partial salvage low-dose-rate brachytherapy used to treat local recurrence after permanent prostate brachytherapy is well-tolerated, with high biochemical response rates. This treatment can be not only a method to delay chemical castration but also a curative treatment option in cases of local recurrence of prostate carcinoma after seed implantation.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival

Purpose: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. Materials and methods: Following our institution’s treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. Results: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1–2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. Conclusions: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.