5-year Biochemical Recurrence-free Survival Rates Research Articles

Clinical and Dosimetric Comparison Between Non-image Guided Radiation Therapy and Fiducial-Based Image Guided Radiation Therapy With or Without Reduced Margin in Intensity Modulated Radiation Therapy for Prostate Cancer

PurposeThis study aimed to compare the outcomes and toxicities between patients treated with image-guided radiation therapy (IGRT) using fiducial markers and non-IGRT in intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and MaterialsIn total, 518 patients with intermediate- and high-risk prostate cancer received IMRT with 78 Gy in 39 fractions after neoadjuvant androgen deprivation therapy for at least 3 months. Of these patients, 371 were in the non-IGRT group and 147 in the IGRT group, including the IGRT-A group using the same margins as the non-IGRT group and the IGRT-B group using reduced margins. The median follow-up periods for the non-IGRT, IGRT-A, and IGRT-B groups were 99 months, 88 months, and 63 months, respectively. Results: The 5-year biochemical recurrence-free survival rates in the non-IGRT, IGRT-A, and IGRT-B groups were 88%, 95%, and 98% (non-IGRT vs. IGRT-A: p = 0.396, IGRT-A vs. IGRT-B: p = 0.426), respectively. Those for intermediate- and high-risk patients were 94%, 93%, and 96% (non-IGRT vs. IGRT-A: p = 0.916, IGRT-A vs. IGRT-B: p = 0.646) and 87%, 96%, and 100% (non-IGRT vs. IGRT-A: p = 0.500, IGRT-A vs. IGRT-B: p = 0.483), respectively. For the non-IGRT and IGRT-A groups, the rates of acute grade ≥ 2 gastrointestinal (GI) toxicities and late grade ≥ 2 genitourinary (GU) toxicities were 17% and 7% (p = 0.019); and 28% and 16% (p = 0.028), respectively. In the IGRT-A and IGRT-B groups, the rates of acute grade ≥ 2 GU toxicities were 45% and 21% (p = 0.003). All V60Gy and V70Gy values of the bladder and rectal walls in the IGRT-B group were smaller than those in the IGRT-A group. Conclusions: IGRT with fiducial markers results in lower acute and late toxicities compared with non-IGRT in IMRT for intermediate- and high-risk prostate cancer. Moreover, the toxicities are further decreased by reducing the margins in the treatment planning under IGRT. These processes do not decrease the biochemical recurrence-free survival rates.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. The median follow-up period was 28.0months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Direct Comparison of Two Different Definitions with Biochemical Recurrence after Low-Dose-Rate Brachytherapy for Prostate Cancer

We aimed to determine whether biochemical recurrence-free survival (BRFS) of patients with prostate cancer (PCa) who received low-dose-rate brachytherapy (LDR-BT) differed according to the definition of biochemical recurrence (BCR) after radical prostatectomy (RP) and the definition given by the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). We reviewed the clinical records of 476 consecutive patients with PCa who received LDR-BT at the Gifu University Hospital. The primary endpoint of this study was the difference in BRFS between the two aforementioned definitions. When the follow-up period ended, 74 (15.5%) and 20 (4.2%) patients had BCR according to the RP and J-POPS definitions, respectively. The 5-year BRFS rates were 85.0% and 96.9% for the RP and J-POPS definitions, respectively (p < 0.005). According to the RP definition, the 5-year BRFS rates were 80.6% in the group aged <63 years and 86.6% in those aged ≥63 years (p = 0.050). According to the J-POPS definition, the 5-year BRFS rates were 94.1% and 97.8% in the groups aged <63 years and ≥63 years, respectively (p = 0.005). The definition of recurrence in LDR-BT may need to be reconsidered.

Patient age as a predictive factor in biochemical recurrence following brachytherapy: Oncological outcomes at a single center.

Iodine-125 low-dose-rate brachytherapy (LDR-BT) is a treatment modality utilized in both localized and advanced prostate cancer (PCa). We aimed to evaluate the long-term oncological outcomes in patients with PCa who underwent LDR-BT, at a single institution in Japan. We retrospectively reviewed the clinical records of 340 consecutive patients with localized PCa who underwent LDR-BT between August 2004 and December 2014 at our institution. Patients with low-risk PCa who had a pretreatment prostate volume >50mL received neoadjuvant androgen deprivation therapy (ADT) for at least 3months before LDR-BT. Patients with intermediate-risk PCa were treated with a combination of LDR-BT and/or external beam radiation therapy (EBRT) and/or ADT for 9months. Patients with high-risk PCa underwent LDR-BT, EBRT, and ADT for 24months. The endpoints of this study were biochemical recurrence-free survival (BRFS) and overall survival (OS). Additionally, the association between biochemical recurrence (BCR) and clinical/pathological covariates was analyzed. At the end of the follow-up period, nine patients (2.6%) showed BCR, and six patients (1.8%) developed secondary cancers after LDR-BT. The 5-year and 10-year BRFS rates were 99.4% and 95.3%, respectively. Factoring in the patients' ages, the 5-year and 10-year BRFS rates were 99.1% and 99.1%, respectively, in patients aged >63years. The rates were 100% and 89.4% in those aged ≤63years, respectively. In the multivariate analysis, age ≤63years was identified as a significant independent predictor of BCR after LDR-BT. Age ≤63years was a significant predictor of BCR following LDR-BT. Although the risk of secondary malignant neoplasms should be considered when opting for LDR-BT in younger patients with PCa, the prevalence of them in these patients is relatively low. Therefore, clinicians should weigh the risks and benefits of definitive therapy in PCa, particularly in younger patients.

Nomogram Predicting Adverse Pathology Outcome on Radical Prostatectomy in Low-Risk Prostate Cancer Men

ObjectiveTo develop and validate a prediction model to predict the risk of adverse pathology outcome on final pathology in low-risk prostate cancer (PCa) men. Materials and MethodsThis study was a monocentric retrospective analysis of 426 men who underwent radical prostatectomy (RP) for low-risk PCa. The validation cohort included 103 men from another hospital. Adverse pathology outcome was defined either by upgrading on RP Gleason Score (GS) (from GS 3+3 to GS ≥ 3+4 with Gleason pattern 4 ≥ 10%) or a non-organ confined disease (pathologic stage ≥ pT3a). Multivariable logistic regression analysis was performed to build nomogram for predicting adverse pathology outcome. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of adverse pathology outcome in the external cohort. The Kaplan-Meier method was used to estimate and compare the biochemical recurrence-free survival rates between the two groups. ResultsOf 426 men in the development cohort, 45.7% showed adverse pathology outcome on RP. Age, body mass index, prostate specific antigen density, history of prior negative biopsy, magnetic resonance imaging prostate imaging reporting and data system score 4-5 and percentage of positive biopsies were significant predictors in multivariate analysis. A nomogram was constructed with an area under curve of 87%. There was agreement between predicted and actual rates of adverse pathology outcome in the validation cohort. The 5-year biochemical recurrence-free survival rates in patients with and without adverse pathology outcome was 70% and 98%, respectively. ConclusionThis novel nomogram would help identify low-risk PCa men at risk of adverse pathology outcome and can be relevant for treatment decision-making.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

Grading of Multifocal Prostate Cancer Cases in which the Largest Volume and the Highest Grade Do Not Coincide within One Lesion.

In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis. We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years. Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively). Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

Therapeutic Consequences of Omitting a Pelvic Lymph Node Dissection at Radical Prostatectomy when Grade and/or Stage Increase

To analyze the effect on biochemical recurrence (BCR) of omitting PLND in subsequently upgraded/upstaged patients (pNx regret). Using nomograms, patients with low to intermediate-risk prostate cancer can be selected to omit a pelvic lymph node dissection (PLND) at the time of a radical prostatectomy (RP). However, some patients will experience upgraded pathology and/or stage. We searched a prospectively maintained single institution/multi-surgeon cohort of patients treated by RP and >5-year follow-up. From 2006-2012, 1026 (521 pNx and 505 pN0/1) eligible patients with biopsy Gleason Score ≤3+4 and cT1c-cT2 undergoing RARP were included in the study. Gleason upgrading from ≤3+4 to >3+4 and/or pT3-4 occurred in 17% of pNx and 32% of pN0/N1 (p<0.001). BCR occurred in 5% of the pNx, and 7% of the PLND group. Five-year BCR free survival was higher in the pNx group (94.7% vs. 91%, P = .048). BCR occurred in 3% in the non-pNx regret and 18% in the pNx regret patients. However, with propensity score matching with pNx regret and pN0/N1 patients, 5-year BCR free survival rates were similar (81% vs 77%, P = .466). Low to favorable intermediate-risk patients who PLND was omitted and experienced upgrading or upstaging (pNx regret), have a higher predicted BCR. However, when matched to a similar cohort with pN0/N1, the BCR did not differ. Omission of a PLND does not appear to alter the rates of BCR compared to PLND inclusion.

Indocyanine green guidance improves the efficiency of extended pelvic lymph node dissection during laparoscopic radical prostatectomy.

To evaluate whether indocyanine green guidance can improve the quality of extended pelvic lymph node dissection in patients undergoing radical prostatectomy. A total of 214 patients underwent laparoscopic radical prostatectomy with indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection. These patients (groupA) were matched 1:1 for clinical risk groups according to the National Comprehensive Cancer Network classification with patients who underwent the same procedure without fluorescence guidance (groupB). Biochemical recurrence was defined as two consecutive prostate-specific antigen rises of at least 0.2ng/mL. The Kaplan-Meier method and Cox regression models were used to identify predictors of biochemical recurrence. The median number of retrieved nodes was significantly higher in groupA (22 vs 14, P<0.001). The rate of lymph node metastases was higher in groupA (65.9% vs 34.1%, P=0.01). Increasing the yield of lymph node dissection was independently and negatively correlated with the biochemical recurrence risk in both overall and pN-positive patients (hazard ratio 0.97, P=0.03; and hazard ratio 0.95, P=0.02). The 5-year biochemical recurrence-free survival rates were (75.8% vs 65.9, P=0.09) and (54.1% vs 24.9%, P=0.023) for groupA and groupB in the overall cohort and pN-positive cohort, respectively. Indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection improves identification of lymphatic drainage, resulting in a higher number of lymph nodes and retrieved lymph node metastases, and allowing a more accurate local staging and a prolonged biochemical recurrence-free survival.

The efficacy and tolerability of ultra-hypofractionated radiotherapy in low-intermediate risk prostate cancer patients: single center experience

Background We aimed to investigate the efficacy and tolerability of ultra-hypofractionated radiotherapy (UHRT) in the treatment of low and intermediate-risk prostate cancer patients. Methods This retrospective study was conducted using data derived from 44 patients who underwent UHRT, and toxicity assessment and clinical response were investigated. Treatment consisted of 35–36.25 Gy in 5 fractions using stereotactic ablative radiotherapy (SABR) with the Linac-based delivery system. Results The median duration of follow-up was 52 months (8–68 months) and the median age was 71.5 years (54–85 years). Twenty-seven patients were assigned as intermediate-risk, whereas 17 patients had low-risk. The 5-year overall survival rate was 87.8%, while the 5-year biochemical recurrence-free survival (bRFS) rate was 97.4%. Acute grade 3 genitourinary (GU) side effect was not observed in any patient, whereas acute gastrointestinal (GI) system grade 3 side effect was seen in 6.8% of the patients. Late grade 3 GU and GI side effects were seen in 4.6% and 6.8% of the patients, respectively. In patients with planning target volume (PTV) ≥85 ml, acute grade ≥2 GU side effects were more common (p=.034). Conclusion Our data demonstrated that UHRT administered with volumetric arc therapy (VMAT) can be recommended for selected patients with low-intermediate risk prostate cancer. Further prospective, multicentric, controlled trials on larger series are warranted to reach more accurate conclusions.

Statin use and risk of prostate cancer biochemical recurrence after radical prostatectomy

BackgroundMultiple studies have investigated the role of statins in prostate cancer (CaP), the leading cause of cancer related death in men. Retrospective cohort studies investigating the correlation between statin use and biochemical recurrence free (BCRF) survival in men with CaP have been inconclusive. ObjectivesIn the largest reported surgical cohort to date, we investigated the effect of statin therapy on BCRF and overall survival in patients with CaP who have undergone radical prostatectomy (RP). Patients and methodsWe performed a retrospective analysis of men (n = 3,088) participating in the NCI funded Specialized Program of Research Excellence (SPORE) in CaP at Northwestern University (NM) in Chicago, Illinois. Patients were treated with RP between 2002 and 2015. Patients in the statin users group received treatment within 2 years prior to or subsequent to RP. Wilcoxon rank-sum and Fisher's exact tests were used to compare age, race, Gleason score, clinical staging, and pathological stage between statin users and nonstatin users. ResultsThe analysis identified 1,222 statin users and 1,865 nonusers (mean age 71 years, 92% Caucasian). After a median follow-up time of 49.0 months, the 5-year BCRF survival rate was 93.3% (95% confidence interval [CI]: 91.9–94.8%) among statin users and 88.6% (95% CI: 87.1%–90%) among nonusers (log-rank P< 0.001). After 10 years, the progression-free survival (PFS) was 91.7% (95% CI: 90.1%–93.3%) among statin users and 86.5% (95% CI: 84.4%–88.2%) among nonusers (log-rank P< 0.001). ConclusionsExtended follow-up data in this large surgical cohort show statin use improves BCRF but not overall survival in RP patients.

Outcomes of Laparoscopic Radical Prostatectomies by a Single Surgeon Alternating Operating Position

The clinical outcome of laparoscopic radical prostatectomy (LRP) was retrospectively investigated taking into consideration the surgeon's position during the procedure. The study cohort included 184 consecutive patients who had undergone LRP performed by a single surgeon from February 2013 to July 2018. During the study period,the surgeon stood alternately on either the left or right side of the patient. The D'Amico risk classification was low,intermediate and high in 26 (14.1%),45 (24.5%) and 113 (61.4%) patients,respectively. Mean surgical duration was 203.5 minutes and mean estimated blood loss was 437.6 ml. Nerve sparing (NS) was implemented in 82 (44. 6%) patients. The mean period of having an indwelling urethral catheter was 5. 0 days. Perioperative Clavien-Dindo degree ≥IIIa complications occurred in three (1.6%) patients. Except for cases with presurgical hormonal treatment,surgical margins were positive in 41 (22.3%) patients,among whom 23 (17.4%) had pT2 disease. The 5-year biochemical recurrence-free survival rate was 81.4%,and 84.8% of patients regained urinary continence at 12 months after surgery. Where the surgeon stood during LRP was not associated with significant differences in any parameter. However,the margin positive rate was higher on the side away from where the surgeon stood than the side closer to the surgeon (70.7% vs 29.3%). In conclusion,the position of the surgeon during LRP does not influence the outcome.

Cohort study of high-intensity focused ultrasound in the treatment of localised prostate cancer treatment: Medium-term results from a single centre.

We report medium-term results in men receiving primary whole-gland HIFU (WG-HIFU) and following salvage treatment. One hundred and twenty-eight patients in a single hospital were enrolled. The enrolled patients were treated with WG-HIFU for primary localized prostate cancer. Salvage treatment include androgen deprivation therapy, secondary HIFU and salvage radiation therapy. Our primary outcomes were biochemical recurrence-free survival, salvage treatment-free survival, and metastasis-free survival. Secondary outcomes included urinary incontinence, de novo erectile dysfunction, acute epididymitis, bladder neck contracture, and urethral stricture. The 5-year biochemical recurrence-free survival rates were 85.7%, 82.7%, and 45.2% for D'Amico low-, intermediate-, and high-risk groups, respectively. Multivariate analysis revealed high risk group is the only predictor of significant shorter biochemical recurrence free survival, salvage treatment free survival, and metastasis free survival. Of 38 patients receiving salvage treatment after biochemical recurrence, 29 (76.3%) became free from biochemical recurrence. Rates of the adverse events of urinary incontinence, acute epididymitis, bladder neck contracture or urethral stricture, and de novo erectile dysfunction were 2.3%, 10.9%, 20.3%, 65.6%, respectively. In conclusion, WG-HIFU is an effective treatment option for localised prostate cancer, especially in D'Amico low- and intermediate-risk cases. The success rate of salvage treatment with radiation therapy and secondary HIFU for biochemical recurrence was acceptable. Fewer adverse events were caused by HIFU, especially incontinence and erectile dysfunction, than by radical prostatectomy and radiotherapy.

Does Time Spent on Active Surveillance Adversely Affect the Pathological and Oncologic Outcomes in Patients Undergoing Delayed Radical Prostatectomy?

Pathological and oncologic outcomes of delayed radical prostatectomy following prostate cancer active surveillance are not well established. We determined the pathological and oncologic outcomes of favorable risk, Grade Group 1, prostate cancer managed with active surveillance and progressing to radical prostatectomy for clinically significant prostate cancer (Grade Group 2 or greater). Between 1992 and 2015, 170 men with favorable risk prostate cancer underwent delayed radical prostatectomy for clinically significant prostate cancer (ASRP) at the Princess Margaret Cancer Centre. Pathological and oncologic outcomes of the ASRP cohort were compared with a matched cohort treated with up-front radical prostatectomy (405) immediately before surgery. Biochemical recurrence-free survival, overall survival and cancer specific survival were compared. We examined the association between delayed radical prostatectomy and adverse pathology at radical prostatectomy and biochemical recurrence using logistic and Cox regression analyses, respectively. Median time spent on active surveillance before radical prostatectomy was 31.0 months. At radical prostatectomy pT3 (extraprostatic extension, seminal vesicle invasion), positive surgical margin and pN1 rates were comparable between the 2 cohorts. Median followup after radical prostatectomy was 5.6 years. The 5-year biochemical recurrence-free survival rate in the ASRP cohort and up-front radical prostatectomy cohort were 85.8% and 82.4%, respectively (p=0.38). Overall survival and cancer specific survival were comparable between the 2 groups. Delayed radical prostatectomy was not associated with adverse pathological outcomes and biochemical recurrence on regression analyses. Curative intent radical prostatectomy after a period of active surveillance results in excellent pathological and oncologic outcomes at 5 years. A period of active surveillance does not result in inferior outcomes compared to patients with similar risk characteristics undergoing up-front radical prostatectomy.

The significance of micro-lymphatic invasion and pathological Gleason score in prostate cancer patients with pathologically organ-confined disease and negative surgical margins after robot-assisted radical prostatectomy.

The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.

Multimodal treatment for high-risk locally-advanced prostate cancer following radical prostatectomy and extended lymphadenectomy.

The aim of this study was to prospectively evaluate the safety and oncologic outcomes of multimodal treatment in high risk-locally advanced prostate cancer patients (PCa). High-risk-locally advanced prostate cancer patients without distant metastases before radical prostatectomy (RP) were included. Adjuvant high-dose intensity-modulated radiation therapy (IMRT) with concurrent docetaxel and long-term androgen-deprivation therapy (ADT) were started after 3-6 months from RP. ADT was maintained for two years. Acute and late toxicity were evaluated with the Common Terminology Criteria for Adverse Events (v. 3.0). Biochemical and clinical recurrence-free survival were explored by using the Kaplan-Meier method. Overall 42 patients were included. Acute genitourinary toxicity was observed with Grade I, II, and III in four (9.5%), two (4.8%), and one (2.3%) patients, respectively. Acute gastrointestinal toxicity was reported to be of Grade I and II in 12 (29.3%) and three (7.2%) patients, respectively. In these patients, concomitant genito-urinary and gastrointestinal toxicity occurred in three (7.2%) cases. A residual GU Grade I toxicity was present only in one patient. Toxicity due to CHT was found in four (9.5%) patients. Complete continence after RP and IMRT was achieved in 32 patients (76.2%). After a median follow-up of 3.4 years, BCR and clinical recurrence were observed in 16.7% and 9.5% of patients, respectively. A 5-year biochemical and clinical recurrence-free survival rate were 70.7% and 84.0%, respectively. Five-year overall survival was 93.6%. None of the patients died for prostate cancer during follow-up. This novel multimodal treatment paradigm for high-risk locally advanced prostate cancer has an acceptable level of toxicity and good oncological outcomes observed after a long follow-up.

Clinical outcome of high dose rate brachytherapy with external beam radiotherapy for high-risk prostate cancer: a single institutional retrospective study

: This study investigated the clinical outcome of neoadjuvant androgen deprivation therapy followed by high dose rate brachytherapy (HDR-BT, called NEH) with external beam radiotherapy (EBRT) in high-risk prostate cancer (PCa) patients in our institution. : From 2007 to 2012, 192 high-risk PCa patients underwent neoadjuvant treatment-EBRT-NEH ( n = 192). Relations between clinical factors (prostate-specific antigen; PSA, cT stage, Gleason score) and biochemical recurrence were retrospectively analyzed. : The 5- and 7-year overall survival rates were 97.9 and 91.1%. By PSA levels (PSA 20 ng/ml, 20 ng/ml < PSA≤50 ng/ml and PSA > 50 ng/ml), 5-year biochemical recurrence-free survival rates were 85.7, 84.7 and 54.5%, respectively. There were no significant differences between biochemical recurrence and cT stage or Gleason score. : We found that NEH can contribute to better biochemical recurrence free survival of high-risk PCa patients with PSA below 50 ng/ml. High-risk PCa patients with PSA over 50 ng/ml may require more aggressive local or systemic treatment.

The impact on oncological outcomes after radical prostatectomy for prostate cancer of converting soft tissue margins at the apex and bladder neck from tumour-positive to -negative.

To assess the impact of conversion from histologically positive to negative soft tissue margins at the apex and bladder neck on biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) after radical prostatectomy (RP) for prostate cancer. The records of 2 013 patients who underwent RP and intra-operative frozen section (IFS) analysis between July 2007 and June 2016 were reviewed. IFS analysis of the urethra and bladder neck was performed, and if malignant or atypical cells remained, further resection with the aim of achieving histological negativity was carried out. Patients were divided into three groups according to the findings: those with a negative surgical margin (NSM), a positive surgical margin converted to negative (NCSM) and a persistent positive surgical margin (PSM). Among the 2 013 patients, rates of NSMs, NCSMs and PSMs were 75.1%, 4.9%, and 20.0%, respectively. The 5-year BCRFS rates of patients with NSMs, NCSMs and PSMs were 89.6%, 85.1% and 57.1%, respectively (P < 0.001). In both pathological (p)T2 and pT3 cancers, the 5-year BCRFS rate for patients with NCSMs was similar to that for patients with NSMs, and higher than for patients with PSMs. The 7-year DMFS rates of patients with NSMs, NCSMs and PSMs were 97.8%, 99.1% and 89.4%, respectively (P < 0.001). Among patients with pT3 cancers, the 7-year DMFS rate was significantly higher in the NCSM group than in the PSM group (98.0% vs 86.7%; P = 0.023), but not among those with pT2 cancers (100% vs 96.9%; P = 0.616). The 5-year BCRFS rate for the NCSM group was not significantly different from that of the NSM group among the patients with low- (96.3% vs 95.8%) and intermediate-risk disease (91.1% vs 82.8%), but was lower than that of the NSM group among patients in the high-risk group (73.2% vs 54.7%). Conversion of the soft tissue margin at the prostate apex and bladder neck from histologically positive to negative improved the BCRFS and DMFS after RP for prostate cancer; however, the benefit of conversion was not apparent in patients in the high-risk group.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group1, prostate-specific antigen screening; group2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups1 and 2, respectively. Group2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical Tstage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group1 and 71.0% for group2 (P<0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P<0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological Tstage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.