Risk Of Biochemical Recurrence In Patients Research Articles

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis

BackgroundWe compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). MethodsWe performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan–Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. ResultsKaplan–Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). ConclusionAmongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial

BackgroundIn the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). ObjectiveTo assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. Design, setting, and participantsThis is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). Outcome measurements and statistical analysisEach 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. Results and limitationsFrom December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3–42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64–0.75] vs 0.63 [0.57–0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). ConclusionsPresurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). Patient summaryThe use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

Impact of Statin Use on Localized Prostate Cancer Outcomes after Radiation Therapy: Long-Term Follow-Up.

Simple SummaryStatins represent a promising class of agents to improve clinical outcomes of prostate cancer patients treated with radiotherapy, but the results of numerous studies are contradictory. We aimed to assess the impact of statin use on biochemical recurrence in a large database of patients of different risk groups undergoing different modalities of radiation therapy. We evaluated 3555 patients treated with curative external beam radiotherapy, low-dose-rate seed brachytherapy, or external beam radiotherapy plus high-dose-rate brachytherapy. We found no improvement in biochemical recurrence-free survival in statin users, regardless of radiotherapy modality. Our study underlines the need to search for biomarkers that predict an additive effect of statins and determine which patients treated with radiotherapy may benefit from statins as an anticancer drug.The impact of statin use on localized prostate cancer (PCa) remains controversial, especially for patients treated with radiation therapy. We assessed the impact of statin use on biochemical recurrence (BCR) in patients treated for PCa with different modalities of radiation therapy. We evaluated 3555 patients undergoing radiation therapy between January 2001 and January 2022. The impact of statin use on BCR was analyzed for three treatment groups: external beam radiotherapy (EBRT), low-dose-rate seed brachytherapy (LDR), and EBRT plus high-dose-rate brachytherapy (EBRT + HDR). Median follow-up was 52 months among 1208 patients treated with EBRT, 1679 patients treated with LDR, and 599 patients treated with EBRT + HDR. A total of 1544 (43%) patients were taking a statin at the time of treatment, and 497 (14%) patients were in the D’Amico high-risk group. Only intermediate-risk patients treated with LDR fared better with statin use in univariate analysis (p = 0.025). This association was not significant in multivariate analysis (HR 0.44, 95% CI 0.18–1.10, p = 0.06). Statin use was not associated with a reduced risk of BCR in patients treated with radiation therapy. In the era of precision medicine, further investigation is needed to assess the benefit of statins in well-defined patients.

MP11-09 ADDED VALUE OF RADIOLOGICAL TUMOR STAGE IN PREDICTING EARLY ONCOLOGICAL OUTCOMES IN PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY WITHIN CLINICAL STAGE: A STAGE-BY-STAGE ANALYSIS

MP11-09 ADDED VALUE OF RADIOLOGICAL TUMOR STAGE IN PREDICTING EARLY ONCOLOGICAL OUTCOMES IN PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY WITHIN CLINICAL STAGE: A STAGE-BY-STAGE ANALYSIS

MP74-05 OUTCOMES OF NEOADJUVANT CHEMOHORMONAL THERAPY WITH COMPLETE ANDROGEN BLOCKADE, FOLLOWED BY TREATMENT WITH DOCETAXEL AND ESTRAMUSTINE PHOSPHATE BEFORE RADICAL PROSTATECTOMY IN PATIENTS WITH HIGH-RISK LOCALIZED PROSTATE CANCER: A PROPENSITY-SCORE MATCHING ANALYSIS

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (MP74)1 Apr 2020MP74-05 OUTCOMES OF NEOADJUVANT CHEMOHORMONAL THERAPY WITH COMPLETE ANDROGEN BLOCKADE, FOLLOWED BY TREATMENT WITH DOCETAXEL AND ESTRAMUSTINE PHOSPHATE BEFORE RADICAL PROSTATECTOMY IN PATIENTS WITH HIGH-RISK LOCALIZED PROSTATE CANCER: A PROPENSITY-SCORE MATCHING ANALYSIS Shintaro Narita*, Hiromi Sato, Mizuki Kobayashi, Akane Kikuchi, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Atsushi Koizumi, Ryuhei Yamamoto, Mitsuru Saito, Takamitsu Inoue, Shigeru Satoh, Koji Mitsuzuka, Norihiko Tsuchiya, Chikara Ohyama, Yoichi Arai, Hiroshi Nanjo, and Tomonori Habuchi Shintaro Narita*Shintaro Narita* More articles by this author , Hiromi SatoHiromi Sato More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Akane KikuchiAkane Kikuchi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Sohei KandaSohei Kanda More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Ryuhei YamamotoRyuhei Yamamoto More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Koji MitsuzukaKoji Mitsuzuka More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Chikara OhyamaChikara Ohyama More articles by this author , Yoichi AraiYoichi Arai More articles by this author , Hiroshi NanjoHiroshi Nanjo More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000960.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To investigate the clinical outcomes in patients with high-risk prostate cancer (PCa) treated with neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP). METHODS: Our NCHT protocol involved complete androgen blockade (CAB) followed by 6 cycles of docetaxel (30 mg/m2) plus estramustine phosphate (560 mg). NCHT was given to 60 patients with PCa before RP, and we compared the clinical and pathological outcomes with those of 349 patients with high-risk PCa who underwent RP alone, using propensity score matching (PSM). The data for those who underwent RP alone were obtained from the Michinoku Japan Urological Cancer Study Group database. RESULTS: In the NCHT group, 10.0% achieved pathological complete response, 3.3% had positive surgical margins, and 13.3% developed severe complications (Clavien–Dindo grade ≥III) after RP. The median follow-up duration was 42.5 months and the 5-year biochemical recurrence (BCR)-free survival was 60.1%. In multivariate analysis, pN+ was an independent prognostic factor for BCR (hazard ratio = 5.25, 1.30–21.20; P = 0.020). In PSM, the BCR rate in the NCHT group was significantly lower than that in the RP alone group (P = 0.021). In subgroup analyses, the BCR rate in patients with a single high-risk factor was significantly lower in the NCHT group than in the RP alone group (P = 0.027). CONCLUSIONS: NCHT before RP can reduce the risk of BCR in patients with high-risk PCa, particularly if a single high-risk factor is present. However, the potential for perioperative complications should be considered. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1133-e1133 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shintaro Narita* More articles by this author Hiromi Sato More articles by this author Mizuki Kobayashi More articles by this author Akane Kikuchi More articles by this author Taketoshi Nara More articles by this author Sohei Kanda More articles by this author Kazuyuki Numakura More articles by this author Atsushi Koizumi More articles by this author Ryuhei Yamamoto More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Shigeru Satoh More articles by this author Koji Mitsuzuka More articles by this author Norihiko Tsuchiya More articles by this author Chikara Ohyama More articles by this author Yoichi Arai More articles by this author Hiroshi Nanjo More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...

Significance of tertiary Gleason pattern 5 in patients with Gleason score 7 after radical prostatectomy: a retrospective cohort study.

PurposeTo evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP).Patients and methodsThis retrospective study identified 350 patients who received RP and were graded as GS 7 (3+4 or 4+3) at the West China Hospital from January 2009 to December 2017. Initially, the patients were divided into two groups, TGP5 absence and TGP5 presence, independent of Gleason score. We further stratified the patients by adding the Gleason score into four groups: GS 3+4, GS 3+4/TGP5, GS 4+3, and GS 4+3/TGP5. Cox proportional-hazards models were used to evaluate the association between the status of TGP5 and BCR after adjusting for the confounding factors.ResultsThe risk of BCR was significantly higher in patients with TGP5 when compared to patients without TGP5 (P=0.04, HR=2.17 95%, Cl: 1.03–4.59). For patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3 (P=0.04, HR=2.45, 95% Cl: 1.04–5.76).ConclusionThe TGP5 in patients with GS 7 had strong association with the risk of BCR and was an independent predictor for BCR. Further research on larger data sets is needed to confirm these findings.

Significance of tertiary pattern 5 in patients with gleason score 7 after radical prostatectomy.

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.

The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients with pT2N0 Prostate Cancer? A Multi-Institutional Study

The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients with pT2N0 Prostate Cancer? A Multi-Institutional Study

The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients With pT2N0R0 Prostate Cancer? A Multi-Institutional Study

PurposePerineural invasion (PNI) is a histologic feature that is present in as many as 84% of patients with prostate cancer. The prognostic significance of PNI is controversial, with recent studies yielding contradictory results. This study aims to assess whether PNI, on the surgical pathology of patients with pT2N0M0 disease and with negative surgical margins, is an independent prognostic indicator of the risk of biochemical recurrence. Methods and materialsWe identified 1549 patients who received a diagnosis of margin-negative pT2N0M0 prostate cancer at 3 separate institutions between January 1, 2008 and December 31, 2014. We reviewed the electronic medical records of these patients and collected clinical and histologic data. A multivariable analysis was performed to assess the association between PNI and biochemical recurrence. ResultsOf the 1549 patients identified, 936 (60.4%) had PNI and 96 (6.2%) had biochemical recurrence. The median time until recurrence was 16 months. The median follow-up in patients without recurrence was 26.5 months. PNI was associated with pT2c disease. The proportion of patients with pT2c was 89% in patients with PNI compared with 79% in patients without PNI (P < .001). PNI was also associated with a higher surgical Gleason score (of those with vs without PNI, 21% vs 50% had Gleason score 3 + 3; 62% vs 41% had a Gleason score 3 + 4, 12% vs 5% had a Gleason score 4 + 3; and 5% vs 3% had a Gleason score 8-10; P < .001). On univariate analysis, patients with PNI appeared to be more likely to have disease recurrence (hazard ratio: 1.7; 95% confidence interval, 1.1-2.6; P = .015). However, after adjusting for other variables, there was not a significant association between PNI and recurrence (hazard ratio: 1.1; 95% confidence interval, 0.70-1.8: P = .65). ConclusionsWe found that PNI was not an independent indicator of the risk of biochemical recurrence. Instead, PNI may be an indicator of unfavorable histology such as a high Gleason score or diffuse disease within the prostate in pT2N0 patients.

Modification of biochemical recurrence risk in patients with localized prostate cancer after radical prostatectomy with combined histomorphological changes in the peritumoral zone

Aim. To assess the prognostic significance of histopathological processes in the peritumoral zone with respect to the risk of biochemical recurrence in patients with localized prostate cancer after radical prostatectomy. Methods. Histomorphological studies were conducted in the perifocal area of surgical tissue samples from 309 patients with localized prostate cancer (T1c-2cN0M0) after a radical surgery using light microscopy. Four groups of patients were identified depending on the risk of recurrence. Enzyme immunoassay was used to determine the concentration of prostate-specific antigen in the serum at baseline and every 3 months for two years after the surgery to detect biochemical recurrence. Results. Histomorphological examination of the peritumoral zone made it possible to identify histopathological processes associated with adenocarcinoma in 257 out of 309 (83.2%) patients with localized prostate cancer. The risk of biochemical recurrence of a combination of prostatic adenocarcinoma and prostatic intraepithelial neoplasia-2 increased by 3.3 (p=0.02), and of a combination of adenocarcinoma, neoplasia and chronic inflammation in the perifocal zone increased by 4.5 times (p=0.005) compared to patients without histopathological changes of the peritumoral zone. In combination of prostate adenocarcinoma with neoplasia and chronic inflammation in the peritumoral zone, the number of patients with an intermediate risk of cancer recurrence after surgical treatment increased due to decrease of the proportion of patients with very low and low risk of recurrence of the oncologic disease. Conclusion. The combination of prostate cancer with high-grade prostatic intraepithelial neoplasia and chronic inflammation in the peritumoral zone modifies the risk of biochemical recurrence of cancer after radical prostatectomy.

The perineural invasion paradox: Is perineural invasion an independent prognostic indicator of biochemical recurrence risk in patients with pT2N0 prostate cancer?

6 Background: Perineural invasion is a histologic feature present in approximately 19% of patients with prostate cancer. The prognostic significance of perineural invasion is controversial with recent studies yielding contradictory results. This study aims to assess whether perineural invasion on surgical pathology of patients with pT2N0 disease is an independent prognostic indicator of the risk of biochemical recurrence. Methods: We identified 201 patients with non-metastatic pT2N0 prostate cancer at our institution between 1/1/2008-12/31/2014. We reviewed the electronic medical record of these patients and identified whether the patient had biochemical recurrence (defined as PSA &gt; 0.2 after surgery). A multivariable analysis was then performed using clinical and histological data for each patient to assess the association between perineural invasion and biochemical recurrence. Results: Of the 201 patients identified, 68.1% (137/201) had perineural invasion and 14% (28/201) had biochemical recurrence. Perineural invasion was associated with pT2c disease (p &lt; 0.001), an increased number of positive cores on biopsy (p &lt; 0.001), and a higher surgical Gleason score (p &lt; 0.001). 19% of patients with perineural invasion had disease recurrence compared to 3.1% without perineural invasion (p = 0.001, Hazard ratio of 6.2). After performing a multivariable analysis and accounting for pathologic tumor staging and Gleason score, perineural invasion had a trend towards a significant association with recurrence (p = 0.085, Hazard ratio of 3.2). Conclusions: Perineural invasion may be an indicator of unfavorable histology such as a high Gleason score or more widespread disease rather than an independent prognostic indicator of the risk of biochemical recurrence.

Diabetes and the risk of biochemical recurrence in patients with treated localized prostate cancer: a meta-analysis

Biochemical recurrence (BCR), or an elevation in prostate-specific antigen in men after treatment for localized prostate cancer, is an early indication of clinical progression, distant metastases, and mortality. Correlations have also recently been established between diabetes and the incidence and mortality of prostate cancer. However, it remains unknown whether diabetes may predict BCR. We performed a meta-analysis of published articles to investigate the prognostic value of diabetes for BCR in prostate cancer. Eight studies and 11,923 patients were included in our meta-analysis. The relative risk (RR) and its 95% confidence interval (CI) were calculated. We found no apparent association between diabetes and BCR (adjusted RR 1.04; 95% CI 0.87-1.22). The evidence of this meta-analysis indicates that diabetes is not a predictor of risk of BCR in patients with prostate cancer.

Adverse Pathologic Features at Radical Prostatectomy: Effect of Preoperative Risk on Oncologic Outcomes

BackgroundUp to 30% of patients with low-risk prostate cancer (PCa) are found to have features of aggressive disease at radical prostatectomy (RP). Several predictive nomograms and novel genomic markers have been developed to estimate the risk of adverse pathology in men eligible for active surveillance (AS). However, oncologic risk associated with these findings remains unknown. ObjectiveTo determine if the presence of adverse pathologic features at RP in patients eligible for AS is prognostic of poor oncologic outcome independent of pretreatment risk status. Design, setting, and participantsA total of 2660 patients underwent immediate RP at our institution between 1998 and 2008. Patients were stratified as low, intermediate, or high risk according to the D’Amico clinical risk criteria. Outcome measurements and statistical analysisThe rates of adverse pathology were reported, and the 5-yr risk of biochemical recurrence (BCR) was calculated in the presence of aggressive disease. Results and limitationsThe 5-yr risk of BCR in patients with extracapsular extension (n=937) was 43% (95% confidence interval [CI], 40–46) overall but only 15% (95% CI, 11–22) for those who met the criteria for low risk (n=181). For the 473 patients with pathologic Gleason score 4+3, the risk of recurrence at 5 yr was 41% (95% CI, 37–46) overall, 13% (95% CI, 5–27) for low-risk men (n=41), 41% (95% CI, 35–47) for intermediate-risk men (n=287), and 51% (95% CI, 43–60) for high-risk men (n=145). Limitations include use of BCR as the study end point and surrogate for oncologic outcome in men who received curative treatment. ConclusionsThe presence of pathologically unfavorable disease in patients eligible for AS is not informative as to the safety of this treatment modality. We question the relevance of adverse pathology as the end point for predictive tools designed to guide treatment decisions in low-risk PCa. Patient summaryThe risk of biochemical recurrence associated with adverse pathologic findings at prostatectomy is reduced by approximately 50% in men with clinically low-risk prostate cancer.

Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer

The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer. We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Compared to patients with low staining (≤median) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95% CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95% CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95% CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining. Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.

Biochemical Recurrence After Radical Prostatectomy With or Without Pelvic Lymphadenectomy in Korean Men With High-risk Prostate Cancer

To identify predictors of biochemical recurrence (BCR) after radical prostatectomy with or without standard pelvic lymphadenectomy in Korean men with high-risk prostate cancer. The clinical and pathologic data of 199 patients with high-risk features were reviewed retrospectively. High-risk features were prostate-specific antigen level >20 ng/ml, biopsy Gleason score ≥8 or clinical tumor category ≥2c. All patients were followed up by measuring their prostate-specific antigen levels every 3 months. The median follow-up period was 37.0 months (range: 1.0-143.0). During the follow-up period, biochemical recurrence was observed in 68 patients (34.2%). The 1-, 3- and 5-year biochemical recurrence-free survival rates were 79.6, 61.9 and 49.2%, respectively. Surgical Gleason score ≥8, positive surgical margin, extracapsular extension, and seminal vesicle invasion correlated significantly with biochemical recurrence-free survival (all P < 0.05), but pelvic lymphadenectomy did not. Multivariate Cox's proportional hazard analysis revealed that the only significant independent prognostic factor of biochemical recurrence-free survival was seminal vesicle invasion (P = 0.035, relative risk = 1.81). Men with seminal vesicle invasion appear to have a significantly higher biochemical recurrence risk in patients with high-risk prostate cancer. However, since the natural history of prostate cancer is variable and accurate means of identifying those who will progress are currently available, it will be necessary to conduct further studies to find prognostic parameters that will allow the early identification of high-risk patients who could benefit from early salvage or adjuvant therapy.

Evaluation of B7-H3 Expression as a Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Recurrent Prostate Cancer

The ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) remains less than optimal. Related to this, novel targets for adjuvant therapies are also lacking. Here, we evaluate the association of B7-H3 expression in primary PCa tumors and BCR after SRT. We identified 148 patients who received SRT between July 1987 and July 2003. Expression of B7-H3 in primary PCa tumors was detected using a monoclonal antibody. The staining levels were quantified via visual assessment and categorized as weak, moderate, or marked. Relative risks (RRs) and 95% confidence intervals (CIs) from Cox proportional hazards models were used to examine the association between B7-H3 staining and BCR. With a median follow-up of 6.2 years (minimum, 0.6; maximum, 14.7), 78 patients (53%) experienced BCR. In single-variable analysis, there was evidence of an increased risk of BCR for patients with moderate (RR, 2.25; 95% CI, 1.24-4.09, p = 0.008) and marked (RR, 4.40, 95% CI, 2.29-8.43, p < 0.001) B7-H3 staining compared with weak staining. This evidence remained, albeit weaker, after adjustment for additional clinicopathologic covariates (RR, 1.82, p = 0.068 [moderate vs. weak]; RR, 2.87, p = 0.003 [marked vs. weak]). This is the first report that higher tumor B7-H3 staining in primary PCa tumors is associated with increased risk of BCR after SRT. Future studies involving larger numbers of patients are required to validate these results and also to explore possible means of targeting B7-H3 in an adjuvant setting.