5-year Biochemical Progression-free Survival Research Articles

Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. The 5-year biochemical progression-free survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities.

Effect of Positive Biopsy Core Rate on Low-dose-rate Brachytherapy Outcomes in Intermediate-risk Prostate Cancer.

Intermediate-risk prostate cancer (PCa) is a highly heterogeneous disease. Although low-dose-rate brachytherapy (LDR-BT) is mainly used for low- to intermediate-risk PCa, limited reports have evaluated the detailed differences in outcomes, including differences between patients with ISUP grade group (GG) 2 and GG3 intermediate-risk PCa. This study aimed to investigate the differences in outcomes between intermediate-risk Japanese patients with GG2 and GG3 PCa who underwent LDR-BT. This single-center retrospective study included 342 consecutive patients with intermediate-risk PCa; 232 patients with GG2 and 110 with GG3 were treated with LDR-BT at Tokushima University Hospital between July 2004 and December 2019. No significant difference in 5-year biochemical progression-free survival and cancer-specific survival was observed between patients with GG2 and those with GG3 (p=0.649 and p=0.633, respectively). Multivariate analysis showed that radiation doses up to 90% of the prostate volume (D90) and the percentage of positive cores were predictors of recurrence in all patients with intermediate-risk PCa. Group analyses showed that D90 was a predictor for recurrence in patients with GG2. In contrast, a high percentage of positive cores was a significant risk factor for recurrence in patients with GG3. Positive core ratios observed on prostate biopsy correlated with higher recurrence rates after LDR-BT. This indicates that the proportion of positive cores in the biopsy may be an important factor in predicting the likelihood of recurrence, especially for patients with GG3 PCa.

A tissue miRNA expression pattern is associated with disease aggressiveness of localized prostate cancer.

Prostate cancer (PCa) is a heterogeneous malignancy with high variability in clinical course. Insufficient stratification according to the aggressiveness at the time of diagnosis causes unnecessary or delayed treatment. Current stratification systems are not effective enough because they are based on clinical, surgical or biochemical parameters, but do not take into account molecular factors driving PCa cancerogenesis. MicroRNAs (miRNAs) are important players in molecular pathogenesis of PCa and could serve as valuable biomarkers for the assessment of disease aggressiveness and its prognosis. In the study, in total, 280 PCa patients were enrolled. The miRNA expression profiles were analyzed in FFPE PCa tissue using the miRCURY LNA miRNA PCR System. The expression levels of candidate miRNAs were further verified by two-level validation using the RT-qPCR method and evaluated in relation to PCa stratification reflecting the disease aggressiveness. MiRNA profiling revealed 172 miRNAs dysregulated between aggressive (ISUP 3-5) and indolent PCa (ISUP 1) (p < 0.05). In the training and validation cohort, miR-15b-5p and miR-106b-5p were confirmed to be significantly upregulated in tissue of aggressive PCa when their level was associated with disease aggressiveness. Furthermore, we established a prognostic score combining the level of miR-15b-5p and miR-106b-5p with serum PSA level, which discriminated indolent PCa from an aggressive form with even higher analytical parameters (AUC being 0.9338 in the training set and 0.8014 in the validation set, respectively). The score was also associated with 5-year biochemical progression-free survival (bPFS) of PCa patients. We identified a miRNA expression pattern associated with disease aggressiveness in prostate cancer patients. These miRNAs may be of biological interest as the focus can be also set on their specific role within the molecular pathology and the molecular mechanism that underlies the aggressivity of prostate cancer.

Salvage Radiotherapy Plus Androgen Deprivation Therapy for High-Risk Prostate Cancer with Biochemical Failure after High-Intensity Focused Ultrasound as Primary Treatment.

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6–12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.

Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol

BackgroundSalvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases.MethodsThe PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of < 1.0 ng/mL and a recent negative PSMA PET/CT scan. Participants will be randomised in a 1:1 ratio between the conventional fractionated treatment arm (35 × 2 Gy) and the experimental hypofractionated treatment arm (20 × 3 Gy). The primary endpoint is the 5-year progression-free survival after treatment. The secondary endpoints include toxicity, quality of life and disease specific survival.DiscussionFirstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed.Trial registrationThis study is registered at ClinicalTrials.gov (Identifier: NCT04642027). Registered on 24 November 2020 – Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants.

Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy.

IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and MethodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 – Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

Oncologic outcome of radical prostatectomy versus radiotherapy as primary treatment for high and very high risk localized prostate cancer.

To compare the oncologic outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) ± androgen deprivation therapy for primary treatment of high risk localized prostate cancer (CaP). We retrospectively reviewed a prospectively-populated database for cases who underwent primary treatment for high risk localized CaP, had more than 2 years follow-up, and were treated since 2006. A total of 335 cases were studied of whom 291 underwent RP and 44 underwent EBRT. Clinical characteristics, biochemical progression-free survival (BPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were compared. EBRT cases were older (p < .01; mean 71 years vs. 61 years) and had longer PSA doubling time (PSADT) (p = .03; median 4.8 years vs. 3.5 years) than RP. Race, pretreatment PSA and biopsy Gleason score were similar. Median follow-up was 5.1 (range: 2.3-12.8) years for RP versus 3.3 (range: 2-12.4) years for EBRT. Three- and 5-year BPFS were 42% and 36% after RP versus 86% and 75% after EBRT (p < .01). The rate of adjuvant/salvage therapy was 58% after RP versus 20% after EBRT (p < .01). Three- and 5-year MFS were 80% and 77% after RP versus 91% and 91% after EBRT (p = .11). Three-year CSS was 98% in both groups and OS was 97% after RP versus 94% after EBRT (p = .73). RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer.

Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression-free survival (BPFS) over RP alone. Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS). In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, -0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone. The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.

Elective Node Irradiation With Integrated Boost to the Prostate Using Helical IMRT-Clinical Outcome of the Prospective PLATIN-1 Trial.

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT).Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months.Results: After a median follow-up of 71 months (range: 5–95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes.Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.

Salvage radiation therapy following radical prostatectomy in Stockholm County in 2008–2016

This is a large single-institution report including 714 consecutive prostate cancer patients who received salvage radiation therapy (SRT) between 2008 and 2016 in Stockholm, Sweden. The aim of the study was to determine the PSA outcomes of salvage radiotherapy in a cohort of prostate cancer patients after radical prostatectomy (RP). All patients have been treated with 70 Gy during a 7-week period. STHLM-0 database was the source of all PSA test results in Stockholm. During a median follow-up of 48 months after radiotherapy treatment, 49% of patients had no signs of biochemical failure (BcF), 13% experienced BcF, and 38% never reached PSA nadir and subsequently progressed after SRT. Five-year biochemical free survival (bPFS) was 47%. Low PSA at SRT start as well as low preoperative Gleason score and T-stage were independently associated with favorable 5-year biochemical progression-free survival. Patients who started SRT at PSA < 0.28 ng/ml had the best 5-year bPFS of 58%. Median pre-SRT PSA was 0.28 ng/l (0.2–0.45) indicating the good standard of salvage radiotherapy process from patient referral to start of radiotherapy in Stockholm County.

Outcomes of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

Salvage radiotherapy (SRT) provides effective biochemical control for patients with prostate cancer who have prostate specific antigen (PSA) failure after radical prostatectomy. However, the effect of SRT on long-term clinical outcomes remains unknown. Therefore, we report the natural history of patients treated with SRT. We identified 84 Chinese patients with prostate cancer treated with SRT to the prostatic fossa alone during 2006-2017 at Tuen Mun Hospital, Hong Kong. Survival was calculated using Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters with outcomes. Median SRT dose given was 70 Gy (range, 64-76 Gy). Median pre-SRT PSA level was 0.4 ng/mL (0.2-7.4 ng/mL). After SRT, 47 (56%) patients had undetectable (<0.1 ng/mL) PSA levels. After median follow-up of 48 months (2 months to 10 years), 25 (30%) patients had further biochemical progression. Subsequently, 12 patients received androgen deprivation therapy and nine (11%) developed distant metastasis. The 5-year biochemical progression-free survival, androgen deprivation therapy-free survival and metastasis-free survival were 62.7%, 83.5% and 86.7%, respectively. Early PSA failure after radical prostatectomy (hazard ratio 7.4), negative surgical margin (hazard ratio 2.7), positive extracapsular extension (hazard ratio 4.6), and detectable PSA levels after SRT (hazard ratio 17.3) were associated with lower biochemical progression-free survival after SRT. High-dose SRT with intensity-modulated radiotherapy/volumetric modulated arc radiotherapy is an effective local treatment that can prevent distant metastasis and avoid the need for androgen deprivation therapy in Chinese patients who have PSA failure after radical prostatectomy.

External beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: Whole pelvis or prostate-only EBRT?

86 Background: In high-risk prostate cancer, the risk of occult lymph node metastases in the pelvic lymph nodes can be as high as 40%. However, the use of whole pelvis radiotherapy (WPRT) in high-risk patients remains controversial with mixed retrospective evidence and two negative prospective trials. Data from a national UK database of patients treated with external-beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy was reviewed to evaluate the benefit of pelvic treatment. Methods: From 2009 to 2013, 755 patients with intermediate- and high-risk prostate cancer (clinical stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen (pPSA) ≥10) were treated with EBRT and HDR brachytherapy. The pelvic nodes to the level of the common iliac chain were treated in 370 patients with a dose of 46Gy in 23 fractions. The remaining 385 patients received radiotherapy to the prostate only (PORT) at a dose of 37.5Gy in 15 fractions. A single dose of 15Gy was delivered with HDR brachytherapy in each case. Corresponding biologic effective doses to the prostate were 107Gy and 100Gy respectively (α/β = 1.5). 96.5% of patients received ADT with a median duration of 24 months. Biochemical failure was defined as a PSA rise of ≥2ng/ml above nadir. Analysis used log-rank and Cox univariate and multivariate tests. Results: Median follow-up was 4.5 years; 5-year biochemical progression-free survival rates for the WPRT versus the PORT arms were 88% vs 80% (p &lt; 0.05) for all patients and 89% vs 76% (p &lt; 0.05) for high-risk patients. Differences in bPFS remained significant (p &lt; 0.05) after accounting for Gleason score, pPSA, T stage and ADT duration as co-variates. There was no difference in overall survival. Conclusions: Whole pelvis EBRT with HDR brachytherapy appears to significantly improves 5-year biochemical progression-free survival in intermediate- and high-risk prostate cancer compared to prostate-only EBRT and HDR brachytherapy which persists after allowing for covariates including presenting tumour parameters and ADT use. The PIVOTAL boost trial in the UK will assess this further in a prospective randomised study.

Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer

Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2ng/mL. A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6months (LRC), 59.2months (IRC), 74.9months (LRB), and 59.8months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001).The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was-35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.

High-dose-rate brachytherapy boost in prostate cancer: a New Zealand case series

AbstractAimThe aim of the present study was to report the survival outcomes and late toxicity of high-dose-rate brachytherapy (HDRBT) boost for dose escalation in patients with intermediate-to-high-risk prostate cancer.Materials and methodsRetrospective data were collected from 137 patients who had undergone definitive radiotherapy for prostate cancer between 2006 and 2010. All patients had external-beam radiotherapy (median dose 46Gy) and HDRBT. Brachytherapy dose was 19Gy in two fractions (6 hours apart) with one implant using Ir-192.ResultsThere were 94 high-risk and 43 intermediate-risk patients (NCCN classification). The median follow-up period was 60 months. The 5-year biochemical progression-free survival was 92 and 76% for intermediate- and high-risk groups, respectively. Prostate cancer-specific survival for the intermediate-risk group was 100% and for the high-risk group it was 92% at 5 years. For the entire cohort, the 5-year rate of urethral stricture formation was 13%, and the 5-year rate of late grade 2 and grade 3 gastrointestinal toxicity was 4·7 and 4·6%, respectively. There was no grade 3 or greater genitourinary toxicity.FindingsOur data add to the growing body of literature supporting the use of HDRBT in prostate cancer. Late toxicity rates were marginally higher than that expected.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Biochemical progression-free survival in localized prostate cancer patients treated with definitive external beam radiotherapy.

IntroductionProstate cancer is now the third most frequent noncutaneous malignancy in Iranian men and the fifth most common cancer worldwide. Measurement of total serum prostate specific antigens (PSAs) has been one of the strongest predictors of biochemical progression and overall survival in determining the efficacy of definitive external beam radiation therapy in patients with localized prostate cancer. The aim of this research was to identify the 5-year biochemical progression-free survival (BFS) and related prognostic and predictive factors of localized prostate cancer patients who were treated with definitive external beam radiotherapy.MethodsThis study analyzed 192 localized prostate cancer patients from stage T1aN0M0 to stage T3N0M0; they were treated with definitive radiation therapy and followed up in the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran (Iran) between 2006 and 2013. The 5-year BFS was analyzed using the Kaplan-Meier estimate. For multivariate analysis, the Cox proportional hazards model was used to assess the strengths of various factors for 5-year BFS.ResultsThe follow-up period was between 14–81 months, with a median of 31 months. The median cumulative prostate dose in our series was 64 Gray (Gy) (range 62 to 78 Gy). The 5-year BFS for all patients was 65.1%, and 5-year BFS in low-risk, intermediate-risk and high-risk groups were 100%, 86.5%, and 54.9% respectively. Multivariate analysis found statistically significant relation between 5-year BFS and initial PSA>20, Gleason score 8–10, high risk group, TNM stage≥T2cN0M0, radiotherapy dose<70 Gy, radiotherapy with 2D technique and hormonal therapy in high-risk group (p=0.003, p=0.032, p=0.014, p=0.001, p=0.035, p=0.035, p=0.022 respectively).ConclusionOur seven years’ experience of follow-up with PSA showed that PSA was the strongest predictor of biochemical progression survival in patients with prostate cancer who were treated with definitive external beam radiation therapy.

Oncological outcomes of cryosurgery as primary treatment in T3 prostate cancer: experience of a single centre.

To assess the oncological outcomes and determine prognostic factors for overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (BPFS) after cryosurgery for clinical stage T3 prostate cancer. Between 2002 and 2007, 75 patients with clinical stage T3 prostate cancer received cryosurgery as primary treatment in our institution. No adjuvant treatment was provided until biochemical failure. After biochemical failure, hormone therapy was administered. Kaplan-Meier analysis was used to calculate the OS, CSS, and BPFS. Cox regression was used to identify factors predictive of survival. Clinical stage T3a (cT3a) was detected in 60% (45/75) of patients and cT3b detected in 40% (30/75). The 5-year OS, CSS, and BPFS rates were 85.3%, 92.0%, and 48%, respectively. There was a significant difference when comparing the pT3a with the pT3b group for 5-year OS (88.9% vs 80%, P = 0.02) and BPFS (55.6% vs 36.7%, P = 0.01), but there was no difference in CSS (93.3% vs 90%, P = 0.63). Stage, Gleason score, and nadir prostate-specific antigen (PSA) were associated with BPFS, while Gleason score and nadir PSA were the most significant predictors for CSS. Cryosurgery can offer good 5-year OS, CSS, and BPFS rates for cT3 prostate cancer, and there was no difference between T3a and T3b for CSS. Gleason score and nadir PSA were the most significant predictors of survival. Further clinical trials are warranted for evaluating the role of cryosurgery for cT3 prostate cancer.

Salvage of Locally Recurrent Prostate Cancer After Definitive Radiotherapy

Although a significant proportion of patients with localized prostate cancer are cured after definitive radiotherapy, solitary local recurrence is observed in a subset of patients and poses a management challenge. Curative-intent treatment options include prostatectomy, reirradiation, cryotherapy, and high-intensity-focused ultrasound. Outcomes data after any of these options are relatively limited. The 5-year biochemical progression-free survival rate is approximately 50% after salvage prostatectomy. However, the morbidity rate of the procedure is significantly higher compared with that observed in previously untreated patients. The likelihood of cure after low dose rate brachytherapy is similar to that observed after salvage prostatectomy, and the morbidity, although significant is less. Although cryotherapy and high-intensity-focused ultrasound may be less morbid than a prostatectomy, the probability of cure is probably lower.