Prostate-specific Antigen Failure-free Survival Rate Research Articles

Vesico‐urethral anastomosis sampling: a forgotten tool for guiding salvage radiation after radical prostatectomy

To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.

Prostate-specific antigen dynamics after neoadjuvant androgen-deprivation therapy and carbon ion radiotherapy for prostate cancer.

This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria. The median patient age was 68 (range, 48-81) years. The median follow-up duration was 33 (range, 20-48) months. The clinical T stage was T1c, T2a, and T2b in 27, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33-19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2-117) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6-30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15-33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age and lower T stage were significant predictors of PSA bounce. Younger age was a significant predictor of PSA failure. In this study, we identified the significant predictors of the occurrence of PSA bounce and failure. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

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.

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with T1c-T2N0M0 prostate cancer

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with T1c-T2N0M0 prostate cancer, with initiation of salvage hormonal therapy (SHT) at a relatively early phase, were analyzed. Fifty-nine Japanese patients with T1c-T2N0M0 prostate cancer who received radical 3D-CRT between January 1999 and January 2003 were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were: 72 years, 9.4 ng/ml, and 6 months, respectively. Seventy Gy was given in 35 fractions confined to the prostate ± seminal vesicles. AHT was not administered after 3D-CRT in any patients. The median follow-up period was 89 months. The median PSA value at the time of initiation of SHT was 4.7 ng/ml (range 0.1-21.6 ng/ml). The overall, disease-specific, PSA failure-free (based on the Phoenix definition), and SHT-free survival rates at 8 years were 82.8% (95% confidence interval [CI] 72.4-93.2), 100%, 62.4% (47.1-77.8), and 82.6% (71.3-94.0), respectively. Only one patient developed grade 3 late toxicity. The PSA control rates in our series of Japanese patients with stage T1c-T2N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed at least comparable to those reported from Western countries; as well, the patients had excellent outcomes. The present outcomes can be used as basic data for evaluating the impact of dose escalation with intensity-modulated radiation therapy for Japanese patients with prostate cancer in the future.

Which Patients With Undetectable PSA Levels 5 Years After Radical Prostatectomy Are Still at Risk of Recurrence?—Implications for a Risk-adapted Follow-up Strategy

To determine the predictors of late prostate-specific antigen (PSA) failure among men with an undetectable PSA level 5 years after radical prostatectomy (RP). A total of 505 men who had undergone RP for prostate cancer from 1985 to 2000 at Brigham and Women's Hospital and who had ≥ 5 years of recurrence-free survival (ie, all PSA levels < 0.2 ng/mL) constituted the study cohort. Cox multivariate regression analysis was used to determine the factors associated with PSA failure after 5 years. Kaplan-Meier analysis was used to estimate the PSA failure-free survival rate. The median follow-up was 10.7 years after RP (interquartile range 7.8-13.3). No patient had PSA failure at year 5, but the PSA failure-free survival rate for this cohort at year 10 was 88% (95% confidence interval 84.4%-91.0%) and, at year 13, was 82% (95% confidence interval 77.0%-86.0%). On multivariable regression analysis, the factors associated with failure after year 5 were Gleason score 7 (adjusted hazard ratio [AHR] 1.88, P = .036), Gleason score 8-10 (AHR 4.81, P ≤ .002), extracapsular extension (AHR 2.37, P = .003), and seminal vesicle invasion (AHR 1.52, P = .062). Among men with an undetectable PSA level 5 years after RP, Gleason score 7, Gleason score 8-10, extracapsular extension, and seminal vesicle invasion were significant predictors of subsequent late PSA failure. Patients with these factors (particularly Gleason score 8-10 or seminal vesicle invasion) should have continued close monitoring of their PSA level and consideration of early salvage, as appropriate. However, patients with Gleason score 6 disease were very unlikely to develop late recurrence and might be candidates for less-intense follow-up once they have passed the 5-year mark.

Radical prostatectomy for high‐risk prostate cancer: Biochemical outcome

To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer. Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL. The PSA failure-free survival rate for the high-risk group (n = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) >or=30 was a significant independent predictor of extra prostatic extension. Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.

Risk Stratification of High-grade Prostate Cancer Treated with Antegrade Radical Prostatectomy with Intended Wide Resection

The aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification. A consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan-Meier method and the difference between groups was assessed with log-rank test. Cox's proportional hazards model was used to elucidate predictors of PSA failure. During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups. Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

Lymphovascular invasion is an independent predictor of prostate‐specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer

To investigate the association of lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens with prostate-specific antigen (PSA) failure in patients with pT3aN0 prostate cancer (PCA). We retrospectively reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP alone. All of the 94 patients were prospectively observed without any treatment until PSA failure was confirmed. We investigated the association of LVI with the adverse pathological findings in RP specimens and the PSA failure-free survival rate. The Cox proportional hazard model was used to elucidate predictors of PSA failure. Median follow up was 47.4 months (quartile range 9.1 to 146.8). LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of PSA failure. Stratifying patients into four risk groups by LVI status and PSA level, the PSA failure-free survival rate in patients with negative LVI and PSA < or =10 ng/mL was significantly better than any other groups (positive LVI and/or PSA >10 ng/mL). Adjuvant therapy would not be indicated to patients with pT3aN0 PCA with negative LVI and PSA < or =10 ng/mL.

Deferred combined androgen blockade therapy using bicalutamide in patients with hormone‐refractory prostate cancer during androgen deprivation monotherapy

To assess the effect of adding bicalutamide on serum prostate-specific antigen (PSA) levels in patients with hormone-refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT). Forty-four patients with HRPC were treated with deferred combined androgen blockade (CAB) therapy, administering bicalutamide 80 mg once daily. HRPC was defined biochemically as three consecutive rises in PSA level during ADMT. The treatment response was defined as a > or = 50% decline in PSA levels. Prognostic values of various pretreatment variables for responsiveness to deferred CAB were determined statistically. When the disease relapsed during deferred CAB, bicalutamide was discontinued and the patients were evaluated for the antiandrogen withdrawal syndrome (AWS). Of the 44 patients, 29 (66%) had a PSA response; the median PSA failure-free survival was 9.2+ months. Biopsy Gleason score was the only pretreatment variable predictive of a PSA response (mean Gleason score 7.9 in responders and 8.7 in nonresponders). The PSA doubling time (PSA-DT) was the only statistically significant variable of PSA failure-free survival in a multivariate analysis. The 1- and 2-year PSA failure-free survival rates were 43% and 31% in patients with a PSA-DT of >4 months, while it was 21% and none, respectively, in those with a PSA-DT of <4 months. Responders to deferred CAB had a statistically longer cancer-specific survival than nonresponders. None of 20 patients who were evaluated for AWS had the condition. Deferred CAB therapy using bicalutamide is effective in patients with progression during ADMT, particularly in those with lower Gleason score tumours or a longer PSA-DT. AWS after deferred CAB is uncommon.

Prostate‐specific antigen failure within 2 years of radical prostatectomy predicts overall survival

This study attempts to determine whether prostate-specific antigen (PSA) failure following radical retropubic prostatectomy (RRP) affects patients' long-term overall survival. This study examined 155 men diagnosed as clinical stages T1b-T3a who received RRP as primary therapy. To evaluate whether PSA failure following RRP affects overall survival, the patients were grouped into those who experienced PSA failure within 2 years and those who did not. Clinical failure-free survival, prostate cancer-specific survival and overall survival were used as endpoints. Comparisons of survival curves were performed using the log-rank test. Logistic regression analysis was performed to determine the variable most predictive of PSA failure within 2 years of surgery. At 10 years, the PSA failure-free survival rate, clinical failure-free survival rate, prostate cancer specific survival rate and overall survival rate of the 155 patients were 40.1%, 83.1%, 94.9% and 84.2%, respectively. The overall survival curve for patients with PSA failure within 2 years of surgery was significantly lower than for patients with no PSA failure within 2 years of surgery (P = 0.042). The multivariate logistic regression analysis demonstrated that PSA greater than 20 ng/mL and poor differentiation of the tumor were significant independent predictors of PSA failure within 2 years of surgery. These results imply that prospective studies should be conducted to detect patients at high risk for PSA recurrence in whom metastasis may occur early and to investigate postoperative treatments for these high-risk patients to improve overall survival.

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

The impact of the biopsy Gleason score on PSA outcome for prostate cancer patients with PSA ≤ 10 ng/ml and T1c,2a: implications for patient selection for prostate-only therapy

Purpose: This study was performed to determine the ability of the biopsy Gleason score, prostate-specific antigen (PSA) level, and the 1992 American Joint Commission on Cancer (AJCC) clinical T-stage for predicting time to postoperative PSA failure for patients with a PSA ≤ 10 ng/ml and T1c or T2a disease. Specific attention is given to the patient subgroup with biopsy Gleason 3 + 4 vs. 4 + 3. Methods and Materials: A concordance map of the biopsy and prostatectomy Gleason grades and a clinical–pathologic correlation of the PSA, biopsy Gleason score, and 1992 AJCC T-stage and pathologic stage were performed. A Cox regression multivariable analysis was used to evaluate the ability of the biopsy Gleason score, PSA, and 1992 AJCC T-stage to predict time to PSA failure for 457 men managed with a radical prostatectomy (RP). Results: The absence of prostatectomy Gleason grade 4 or 5 disease was noted in 71%, 50%, and 11% of patients with biopsy Gleason score 2–6, 3 + 4, and ≥ 4 + 3 disease respectively while pathologic evidence of seminal vesicle invasion was noted in 2%, 4%, and 17% of these patients respectively. Estimates of 5-year PSA failure-free survival rates were not statistically different for patients with biopsy Gleason score 2–6 vs. 3 + 4 (79% vs. 81%; p = 0.93), but were significantly different for patients having biopsy Gleason score 2–6 vs. 4 + 3 (79% vs. 62%; p = 0.04) or 2–6 vs. 8–10 (79% vs. 18%; p = 0.0001) prostate cancer. Conclusion: Based on the pathologic stage and PSA control data following RP, patients with biopsy Gleason 3 + 4 disease and PSA ≤ 10 ng/ml and 1992 AJCC T1c or T2a disease may be suitable candidates for radiation therapy directed at the prostate only.