5-year Prostate-specific Antigen Research Articles

Treatment outcome of localized prostate cancer using transperineal ultrasound image-guided radiotherapy

BackgroundWe report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT).MethodsA total of 124 patients (median age: 74 y, 46–84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5–7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76–78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2–3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation.ResultsA total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups.ConclusionThese results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

How long is long enough to secure disease control after low-dose-rate brachytherapy in combination with other modalities in intermediate-risk, localized prostate cancer?

Previous studies have demonstrated excellent overall outcomes in patients who underwent low-dose-rate brachytherapy (LDR-BT) in intermediate-risk, localized prostate cancer (PCa). We thus investigated the appropriate length of time before completing prostate-specific antigen (PSA) monitoring after treatment. Between 2003 and 2014, 710 localized, intermediate-risk PCa patients underwent LDR-BT with or without supplemental external beam radiotherapy (EBRT). Data from 567 of those patients was analyzed in this study. Neoadjuvant hormonal therapy (NHT) was administered to 315 patients (55.6 %) and NHT with adjuvant hormonal therapy (AHT) to 59 patients (10.4 %), as per the protocol of a prospective randomized controlled trial (SHIP0804). We stratified patients by posttreatment PSA levels at specific times and assessed the factors for association with biochemical recurrence (BCR) and for clinical progression (CP). The median follow-up was 109 months (range, 60-205 months). Of 529 patients who were BCR-free at 3 years after treatment, 56 subsequently developed BCR, and 47 developed CP. PSA at 3 and 5 years after treatment were significantly correlated with long-term oncological outcomes. No patients with 5-year PSA levels ≤0.1 ng/mL subsequently developed BCR or CP. Discontinuation of PSA monitoring could be discussed with patients with intermediate-risk PCa as a reasonable option if PSA levels remain ≤0.1 ng/mL at 5 years after LDR-BT, either alone or with other combined modalities, as subsequent recurrences are quite rare.

Salvage treatments for prostate-specific antigen relapse of cT3N0M0 prostatic adenocarcinoma after radical prostatectomy combined with neoadjuvant androgen deprivation

Abstract Objective The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen (PSA) relapse of cT3N0M0 prostatic adenocarcinoma (PCa) after radical prostatectomy (RP) combined with neoadjuvant androgen deprivation (ADT). Methods A total of 332 patients with cT3N0M0 PCa were enrolled in the prospective study and received RP and pelvic lymph node dissection with neoadjuvant ADT for 3 months. All patients with PSA relapse were treated with salvage external beam radiation therapy (RT) and ADT for 6 months. Results The 5-year postoperative PSA relapse rate was 40.96% (136/332). The patients have been divided into the PSA relapse and PSA relapse-free groups in order to compare patient characteristics. The ratio of patients with Gleason score ≥ 8 and positive surgical margin in the PSA relapse group were significantly higher than those of in the PSA relapse-free group (P = 0.01). The mean duration between the start of operative treatment and PSA relapse was 31 months. Salvage treatment to all 136 PSA relapse patients led to favorable outcomes. PSA relapse was not observed after salvage treatment by the end of follow-up. The 5-year overall survival rates of the PSA relapse and PSA relapse-free groups were 94.9% and 93.9%, respectively. Conclusion In pursuit of curative treatment, our study showed that RP combined with neoadjuvant ADT is an aggressive multimodality strategy associated with lower PSA relapse and better survival outcomes for stage cT3N0M0 PCa patients. Patients with PSA relapse after RP may benefit from early aggressive salvage RT combined with short-term ADT.

Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer.

This study aimed to first elucidate prostate-specific antigen (PSA) kinetics in prostate cancer patients treated with carbon ion radiotherapy (CIRT). From 2010 to 2015, 131 patients with prostate adenocarcinoma treated with CIRT (57.6 Gy relative biological effectiveness (RBE) in 16 fractions) alone were recruited. PSA was measured at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post-CIRT. PSA bounce was defined as PSA increase over a cutoff followed by spontaneous decrease to or below the pre-bounce nadir. PSA failure was determined using the Phoenix criteria (nadir + 2.0 ng/mL). As a result, non-failure-associated temporary increase in PSA exhibited two distinct patterns, namely a classical bounce and a surge at one month. PSA bounce of ≥0.2 ng/mL was observed in 55.7% of the patients. Bounce amplitude was <2.0 ng/mL in 97.6% of cases. Bounce occurred significantly earlier than PSA failure. Younger age was a significant predictor of bounce occurrence. Bounce positivity was a significant predictor of favorable 5-year PSA failure-free survival. Meanwhile, a PSA surge of ≥0.2 ng/mL was observed in 67.9% of patients. Surge amplitude was significantly larger than bounce amplitude. Larger prostate volume was a significant predictor of PSA surge occurrence. PSA surge positivity did not significantly predict PSA failure. In summary, PSA bounce was distinguishable from PSA failure with regard to timing of occurrence and amplitude (earlier and lower for bounce, respectively). These data are useful for post-CIRT surveillance of prostate cancer patients.

Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy

PurposeTo compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer. Methods425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds. ResultsAfter a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions. ConclusionAfter CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.

Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy

BackgroundBrachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques. Methods and materialsBetween 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale. ResultsMedian follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%–75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients. ConclusionsThese findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

Adjuvant hormone therapy after radical prostatectomy in high-risk localized and locally advanced prostate cancer: First multicenter, observational study in China.

ObjectivePotential of combined androgen blockade (CAB) has not been explored extensively in Chinese males with prostate cancer (PCa). Therefore, this study evaluated the 2-year prostate-specific antigen (PSA) recurrence rate and quality of life (QoL) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy (HT) after radical prostatectomy (RP).MethodsThis prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor (preoperative PSA>20 ng/mL or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice. Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.ResultsA total of 189 patients (mean age: 66.9±6.5 years) were recruited, among which 112 (59.3%) patients showed serum PSA>20 ng/mL preoperatively. The highest postoperative pathological advancement noticed was from clinical T2 (cT2) to pathological T3 (pT3) (43.9%) stage. The majority of the patients (66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence (15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist (LHRHa) (16.1%), and antiandrogen (19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P QoL score of 119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.ConclusionsAdjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in high-risk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens (AA) or LHRHa therapy. Further long-term therapy (>12 months) significantly improved QoL compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving QoL.

Subcastrate Testosterone Nadir and Clinical Outcomes in Intermediate- or High-Risk Localized Prostate Cancer

It is unclear if additional serum testosterone suppression below the castrate threshold of 50ng/dL improves clinical outcomes in patients with localized prostate cancer undergoing definitive therapy. We examined the association of subcastrate testosterone nadir with prostate-specific antigen (PSA) response and long-term clinical outcomes in 764 U.S. veterans with intermediate- or high-risk localized prostate cancer treated with androgen deprivation therapy and definitive radiation therapy from 2000 to 2015. Patients were categorized into testosterone nadir groups based on the minimum testosterone measurement during continuous gonadotropic-releasing hormone agonist therapy (<20ng/dL vs 20-49ng/dL). Outcomes included PSA response (3-month post-radiation therapy PSA and 2-year PSA nadir; multivariable linear regression) and long-term clinical outcomes (biochemical recurrence, metastasis, and prostate cancer-specific mortality; Fine-Gray competing risk regression). A testosterone nadir of 20 to 49ng/dL was associated with higher 3-month post-radiation therapy PSA compared to <20ng/dL (ß=0.16, 95% confidence interval [CI], 0.06-0.26, P=.001) and higher 2-year PSA nadir (ß=0.12, 95% CI, 0.04-0.21, P=.005). Compared to the <20-ng/dL group, the 20 to 49-ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs 18.3%) and metastasis rates (12.9% vs 7.8%) persisting on multivariable analyses (biochemical recurrence: sub-distribution hazard ratio [SDHR], 1.62 for 20-49ng/dL, 95% CI, 1.07-2.45, P=.02; metastasis: SDHR, 2.19, 95% CI, 1.21-3.94, P=.009). There was a trend toward inferior prostate cancer-specific mortality for the 20 to 49-ng/dL group (SDHR, 1.95, 95% CI, 0.90-4.22, P=.09). Additional serum testosterone suppression below 50ng/dL was associated with improved PSA responses and lower rates of biochemical recurrence and metastasis in this cohort of patients with localized prostate cancer.

High-dose-rate brachytherapy boost for prostate cancer treatment: Different combinations of hypofractionated regimens and clinical outcomes

PurposeTo report the outcomes of our high-dose-rate brachytherapy (HDR-BT) boost experience in localized prostate cancer treated with different combinations of radiation doses and fractionation. Material and methodsBetween 1999 and 2011, 832 patients were treated with different regimens of external beam radiotherapy (EBRT) and HDR-BT. These regimens were converted into three biologically effective dose (BED) groups. The biochemical failure-free survival (BFFS), reported with the phoenix definition and prostate-specific antigen (PSA) >0.2ng/ml at 5-year, genitourinary (GU) and gastrointestinal (GI) toxicities were compared between the groups. ResultsThe 5-, 10-year BFFS for the entire cohort were 94.6% and 92.5%, for overall survival (OS) 96.1% and 80.3% and for prostate cancer-specific survival (PCSS) 99.5% and 97.8%. The percentage of patients with a 5-year PSA level <0.2ng/ml was 68.6%, 78.7% and 86.7% in the BED group of <250, 250–260 and >260Gy (p=0.005) while the 5-year BFFS rates according to phoenix definition were 97.3%, 94.3% and 94.9% for BED group <250, 250–260 and >260Gy (p=0.453). On multivariate logistic regression, patients in the BED>260Gy group were significantly more likely to remain free from 5-year PSA values ≥0.2ng/mL compared with those in the BED<250Gy group (OR: 0.350, p=0.011). Grade≥3 acute GU toxicity was reported in 2 patients (4.7%) for BED>260Gy while grade≥3 late GU toxicity was reported in 6 (1.7%) and 9 (4.9%) patients for 250–260Gy and >260Gy BED groups. ConclusionsThe increase in BED with the hypofractionated regimens correlates with an improvement in biochemical control with of urinary toxicity. This increase in urinary toxicity is small and clinically acceptable.

Relationship of Positive Resection Margin, Cancer Location and Learning Curve after Laparoscopic Radical Prostatectomy

Background: One of surgical goals is decreasing of positive resection margin (PRM). In radical prostatectomy, PRM is important because of prognostic factor. We examine the relationship of PRM, cancer location and learning curve after laparoscopic radical prostatectomy (LRP). Methods: Between May, 2009 and May, 2015, 331 consecutive patients were treated with LRP. The resection margin status, Gleason score, pathological stage, cancer location and diameter were assessed in each surgical specimen, and the independent factors for PRM and prostate-specific antigen (PSA) failure were identified. The learning curve for PRM was calculated and the number of cases until the plateau was obtained. Results: PRM was found in 30.5% of all patients, with 27.7% in the pT2 patients and 39.0% in the pT3 patients. The most common site of PRM was in the apex-anterior. The 5-year PSA failure-free survival rate was 73.9%. In patients with a negative resection margin, the 5-year PSA failure-free survival rate was 81.6%, and in patients with PRM, it was 57.4%. The factors associated with PSA failure-free survival were PRM and elevated PSA. The tumor location was not associated with PSA failure-free survival. The factors associated with PRM were tumor location, nerve sparing procedure, and tumor diameter. When the tumor was localized in the apex-anterior, the rate of PRM was elevated 3-fold comparing the tumor in apex-posterior. The learning curve of all surgeons for obtaining a negative resection margin plateaus after 167 cases. The curve of a single surgeon was more improved than all surgeons and the rate of PRM was 16.7%. Conclusions: PRM was associated with both cancer location and diameter. The learning curve of PRM reached a plateau in about 170 cases. However, PRM can be further reduced. These findings related to LRP outcomes are useful for improvement in surgical techniques and for determining prognosis.

Patients treated with radical prostatectomy with positive digital rectal examination findings in the intermediate-risk group are prone to PSA recurrence.

The present study aimed to evaluate the possibility of performing radical prostatectomy (RP) alone to achieve a radical cure for prostate cancer in the intermediate-risk group. Samples were collected from 638 Japanese patients who underwent antegrade RP between August 1998 and May 2013; subsequently, 157 patients were excluded. According to the D'Amico criteria, the low-, intermediate- and high-risk groups comprised 107, 222 and 152 patients, respectively. The 5-year prostate-specific antigen (PSA) failure-free survival rates in the low-, intermediate-, and high-risk groups were 96.5, 88.9 and 72.6%, respectively (P<0.001; degrees of freedom=2). In the intermediate-risk group, the difference in PSA failure-free survival between the 0<PSA≤10 and 10<PSA≤20 ng/ml, and the biopsy Gleason score 6 and 7 groups were not statistically significant, according to the log-rank test (P=0.2266 and P=0.1329, respectively). However, the difference in PSA failure-free survival between the clinical tumor stage (cT)1c and cT2a/b groups was statistically significant based on the log-rank test (P<0.0001). The results of the multivariate analysis revealed that, of the preoperative characteristics, only the cT was a significant predictor in patients with and without PSA failure (P<0.001). Therefore, patients classified into the intermediate-risk group with cT2a/b stage, according to positive digital rectal examination findings, and are not considered to be likely to achieve a complete cure with RP surgery alone. In summary, for patients meeting these criteria in the intermediate-risk group, RP surgery alone is likely to be insufficient, and other additional treatments may be considered subsequent to RP.

Holmium laser enucleation of the prostate followed by high-intensity focused ultrasound treatment for patients with huge prostate adenoma and localized prostate cancer: 5-Year follow-up.

BackgroundTo evaluate the efficacy of holmium laser enucleation of the prostate (HoLEP) followed by high-intensity focused ultrasound (HIFU) for patients with huge prostate adenoma and localized prostate cancer (CaP) and compare the morbidity and efficacy results with those observed in a similar population treated only with HIFU for a follow-up period of up to 5 years.MethodsThe present retrospective study included 30 CaP patients who underwent HIFU alone and 10 patients who underwent HoLEP followed by HIFU. Selection criteria for this study were no previous treatment for CaP, aged 60 years or older, cT1c-T2N0M0, prostate volume of 30 mL or more, and a follow-up period of 5 years or more. Prostate-specific antigen (PSA) biochemical recurrence-free survival (RFS) rates and functional outcomes including complications and uroflowmetry after HIFU were compared between the HIFU monotherapy and HoLEP + HIFU groups.ResultsThe enrolled patients had a mean age of 70.3 years and 68.8 years in the HIFU monotherapy and HoLEP + HIFU groups, respectively. The 5-year PSA biochemical RFS rates of the two groups were similar (HIFU monotherapy group: 57.2%; HoLEP + HIFU group: 67.5%). The duration of indwelling urethral catheter after HIFU significantly decreased in the HoLEP + HIFU group compared with the HIFU monotherapy group (15.5 ± 2.7 days vs. 27.5 ± 2.3 days, P = 0.022). In terms of functional outcomes, patients who received HoLEP + HIFU had significantly higher maximum (12 months: P = 0.015, 36 months: P = 0.014) and average (36 months: P = 0.002, 60 months: P = 0.047) flow rates than those who received HIFU monotherapy. The frequency of urethral stricture (13.3% vs. 0%), symptomatic urinary tract infection (10.0% vs. 0%), and bladder stone and urethrorectal fistula (3.3% vs. 0%) tended to be higher in the HIFU monotherapy group as compared with the HoLEP + HIFU group.ConclusionThe HoLEP + HIFU treatment decreases urinary catheterization time and improves post-treatment urinary status without additional morbidity.

The prognostic significance of OCT4 expression in patients with prostate cancer

Accumulating evidence suggests that OCT4 participates in tumorigenicity and malignancy in human cancers. However, the prognostic significance of OCT4 expression in prostate cancer (PCa) or predictive significance of OCT4 in docetaxel sensitivity in castration-resistant prostate cancer (CRPC) remains unclear. The aim of this study was to assess the prognostic value of OCT4 expression in PCa. We retrospectively analyzed the clinical records and evaluated the OCT4 expression in 205 patients with PCa who underwent radical prostatectomy. We examined the change of OCT4 expression in 3 patients with CRPC who underwent transurethral resection for local progression before and after docetaxel chemotherapy. OCT4 expression was significantly associated with higher pathological T stage (P < .001). The 5-year prostate-specific antigen recurrence-free survival rate was 56.8% in patients with higher OCT4 expression and 90.6% in patients with lower OCT4 expression (P < .001). Multivariate analysis revealed that high OCT4 expression was an independent prognostic indicator of prostate-specific antigen recurrence (P < .001). Elevated strong OCT4 expression in residual CRPC cells after docetaxel chemotherapy was observed in all CRPC patients, compared with before chemotherapy in corresponding specimens. Higher OCT4 expression represents a clinically relevant predictor of patient prognosis in PCa and may be a new biomarker that will provide additional prognostic information in CRPC when treated with docetaxel.

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. The median follow-up period was 6.5years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

Margin details matter: The prognostic significance of pseudocapsule invasion at the site of involved margin in prostatectomy specimens

BackgroundAn involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate pseudocapsule invasion vs. within the prostate parenchyma proper. MethodsPatients were retrospectively identified for inclusion by clinically localized disease and prostate-specific antigen (PSA) level of<30ng/ml at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/nonsalvage postoperative radiation or hormone therapy, or insufficient follow-up (<12mo). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of pseudocapsule invasion at a site of margin involvement. Disease recurrence was defined as PSA level of≥0.2ng/ml and rising, per contemporary guidelines. Kaplan-Meier method was used for construction of disease control estimate confidence intervals; Cox Proportional Hazards Model was used to compare disease control across groups. ResultsBetween 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had clinical stage T1 and T2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8–9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA level of 5.6ng/ml (85%≤10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the pseudocapsule. At a median follow-up of 68 months (range: 13–137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of pseudocapsule invasion vs. prostate parenchyma were 49% vs. 34%, respectively (P = 0.017; hazard ratio = 1.853). ConclusionsEarly PSA relapse rates are high for patients with involved surgical margin(s) without seminal vesicle or node involvement at prostatectomy; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of pseudocapsule invasion or penetration confers a higher risk of recurrence.

Cessation of Primary Androgen Deprivation Therapy for Men With Localized Prostate Cancer

IntroductionSubstantial numbers of men with localized prostate cancer undergo long-term primary androgen deprivation therapy (ADT). Whether long-term ADT is required for patients with localized prostate cancer, especially elderly men, remains unknown. In the present study, we explored the possibility of ADT cessation after a favorable response to primary ADT in patients with localized prostate cancer. Patients and MethodsWe retrospectively reviewed men with localized prostate cancer who had achieved a good initial response to primary ADT and stopped it thereafter. Prostate-specific antigen (PSA) recurrence was defined as 2 consecutive increases > 4 ng/mL. A total of 34 patients (age, 62-89 years) were followed up for > 24 months after ADT cessation. ResultsThe ADT duration and follow-up period after ADT cessation was 10 to 162 months (median, 33.5 months) and 24 to 95 months (median, 37 months), respectively. PSA recurrence was observed in 10 of 34 patients (29.4%), and the 5-year PSA progression-free rate was 66.2%. PSA recurrence was observed in 100% (6 of 6) and 14.3% (4 of 28) of men who had received ADT for < 16 months and > 16 months, respectively. ADT was reinstated in 5 patients after PSA recurrence; and their PSA levels declined rapidly, and no clinical progression was observed. The 5-year overall and disease-specific survival rate was 65.1% and 100%, respectively. ConclusionADT can be stopped for men with localized prostate cancer, especially elderly men, after a favorable response to primary ADT.

Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

Pathological and biochemical outcomes after radical prostatectomy in men with low‐risk prostate cancer meeting the Prostate Cancer International: Active Surveillance criteria

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Active surveillance has been widely accepted as a treatment tool for low-risk prostate cancer, and use of the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria can select smaller and less aggressive tumours in low-risk disease. The study shows the pathological outcomes of radical prostatectomy for patients with low-risk disease who met the PRIAS criteria. It found that ~20% had unfavourable pathological features and only 30% satisfied insignificant cancer criteria with pT2 stage, a Gleason score ≤6 and tumour volume <2.5 mL. It concludes that close follow-up including repeat biopsy or MRI is necessary to minimize unexpected progression of disease. To assess the effectiveness of the Prostate Cancer Research International Active Surveillance (PRIAS) criteria in identifying indolent cancer. Data from 1268 patients undergoing radical prostatectomy without neoadjuvant therapy were retrospectively reviewed. Within this cohort, patients with low-risk disease (n = 211) were classified according to whether they met (Group A, n = 87) or did not meet (Group B, n = 124) the PRIAS criteria. Pathological upstaging, upgrading, tumour volume and 5-year prostate-specific antigen (PSA) recurrence-free survival were compared between the two groups, and factors that predicted upstaging, upgrading and PSA recurrence were analysed by univariate and multivariate methods. Pathological T3 stage was present in 10.3% of patients in Group A and in 18.5% of patients in Group B (P = 0.08). Gleason score upgrading to 4+3 or greater was seen in 19.5% of Group A and in 29.9% of Group B (P = 0.01). The mean (range) tumour volume was 0.81 (0.03-5.09) mL in Group A and 1.40 (0.04-8.21) mL in Group B (P < 0.01). The rates of insignificant cancer with total tumour volume <2.5 mL, Gleason score ≤6 and stage pT2 were 30.6% in Group A and 15.4% in Group B (P = 0.07). With a median follow-up of 44 months, the 5-year PSA recurrence-free survival rates were 91.2% in Group A and 86.4% in Group B (P = 0.47). In multivariate analysis, PSA density and the PRIAS criteria were independent factors that predicted upstaging. Although use of the PRIAS criteria could select more favourable tumours even in low-risk prostate cancer, about one in five men had unfavourable pathological outcomes and only three in ten had insignificant cancer. Close and careful follow-up is necessary to avoid misclassification or progression of disease, especially during the first few years of active surveillance.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

BackgroundSeveral studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer.MethodsIn total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2–88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months.ResultsThe 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2–3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed.ConclusionsThese medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Quantitative RT‐PCR analysis of PSA and prostate‐specific membrane antigen mRNA to detect circulating tumor cells improves recurrence‐free survival nomogram prediction after radical prostatectomy

Circulating tumor cell (CTC) analysis is a potential new biomarker in prostate cancer. We hypothesize that quantitative detection of CTCs in patients pre- and post-radical prostatectomy (RP) using quantitative TaqMan® fluorogenic RT-PCR will improve the accuracy of the Kattan nomogram to predict the probability of recurrence-free survival (RFS) post-RP. Ninty-two patients who underwent RP between 2004 and 2009 had venous blood samples taken pre- (Day - 1) and post-operatively (Day + 7). We performed quantitative Taqman® RT-PCR to detect circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA. We calculated both the logarithmic ratio of Day + 7/Day - 1 for PSA (PSAr) and PSMA (PSMAr) expression (log(Day+7/Day-1) ) and the Kattan nomogram predicted probability of disease recurrence for each patient. We then analyzed how the AUC-ROC analysis for the Kattan nomogram prediction alone (K) compared to the addition of the PSAr and PSMAr in predicting 5-year RFS. The mean age (years), PSA (ng/ml), and follow-up (mo) was 65.1, 9.13, and 72, respectively. The AUCs for K, PSAr + K, and PSMAr + K were 0.752 (95%CI 0.620-0.860), 0.830 (95%CI 0.740-0.911), and 0.837 (95%CI 0.613-0.923), respectively (P = 0.03). The Kattan 5-year PSA RFS was 75%. The actual 5-year PSA RFS survival rate was 77%. Data from modern quantitative RT-PCR to detect circulating prostate-derived PSA and PSM mRNA pre- and post-RP improves the accuracy of the Kattan nomogram to predict biochemical recurrence.