An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer / 亚洲男科学杂志(英文版)

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Analysis of biochemical failure rate and its influencing factors in patients with high-risk localized prostate cancer after radical prostatectomy / 中华泌尿外科杂志

Objective:To analyze the biochemical failure rate and its predictive factors after radical prostatectomy (RP) in patients with high-risk localized prostate cancer.Methods:The data of 166 patients with high-risk localized prostate cancer who underwent RP surgery in Peking university cancer hospital from January 2015 to November 2021 were retrospectively reviewed. The average age was 65.4±6.2 years old, and the average body mass index (BMI) was 24.86±3.23 kg/m 2. The median prostate-specific antigen (PSA) was 19.84 (10.98, 44.47) ng/ml, PSA density was 0.68 (0.34, 1.32)ng/ml 2, and prostate volume was 31.20 (25.58, 40.23) ml. Biopsy pathology Gleason score according to the International society of Urological Pathology(ISUP) grade group: 18 cases of group 1, 33 cases of group 2, 30 cases of group 3, 51 cases of group 4, and 33 cases of group 5, 1 case was unknown. The percentage of puncture positive needles was (55.4±25.7)%, and the largest linear length of positive lesions was 80.0% (60.0%, 90.0%). Preoperative clinical stage : 14 cases in ≤T 2b stage, 117 cases in T 2c stage, 13 cases in T 3a stage and 22 cases in ≥T 3b stage; 157 cases in N 0 stage, 9 cases in N 1 stage. One hundred and three patients (62.0%) were assessed by traditional imaging and 63(38.0%) were assessed by PSMA PET-CT. The patients underwent laparoscopic radical prostatectomy. 64 patients (38.6%) received neoadjuvant therapy, including 37 received neoadjuvant therapy for 1-3 months, 23 for 4-6 months and 4 for over 6 months. The postoperative pathological characteristics, treatment and prognosis of the patients were analyzed. The primary endpoint was biochemical failure, including biochemical persistence(BCP, defined as PSA≥0.1ng/ml at 4-6 weeks after operation, and confirmed by re-examination at least 1 week interval) and biochemical recurrence(BCR, PSA falling below 0.1ng/ml after operation and then rising ≥0.2 ng/ml without adjuvant therapy or after the end of adjuvant treatment). Results:Compared with preoperative clinicopathological characteristics, 48(28.9%) cases had postoperative pathological ISUP upgrade, 98 (59.0%)cases had T stage upgrade, and 13 (7.8%) cases had N stage upgrade. The rate of positive margins was 53%, and apex margin was the most common positive site (65.9%). The postoperative PSA in 114 patients (68.7%) decreased to less than 0.1ng/ml, of which 74 patients didn't receive the therapy and 40 patients received adjuvant therapy. 52 patients (31.3%) had postoperative PSA more than 0.1ng/ml and among them, 51 cases received salvage treatment. 5 patients (3.0%) underwent PSA progression during adjuvant or salvage endocrine therapy and were considered to have castration resistance. After a median follow-up time of 25.5 (12.0, 40.0) months, 78 patients (48.4%, 78/161) experienced biochemical failure, including 49 BCP and 29 BCR, the median time of biochemical failure was 30.0 (95% CI 14.5-45.5) months. Adjuvant therapy could reduce the rate of BCR (31.1% and 15.8%, P=0.08). Baseline PSA, PSA density, proportion of pathological ISUP ≥4, proportion of pathological T stage ≥T 3a, adjuvant therapy, and positive surgical margins were significantly associated with biochemical failure ( P=0.034, 0.002, 0.004, 0.025, <0.001and 0.047). Multivariate Cox regression analysis showed that adjuvant therapy ( P<0.001, OR=0.12), PSA density ( P=0.03, OR=1.19) and positive surgical margins ( P=0.034, OR=1.80) were independent factors for biochemical failure. Conclusions:Patients with high-risk localized prostate cancer have a high rate of biochemical failure after RP and need to receive RP-based multimodal therapy. Adjuvant therapy, PSA density and positive surgical margins are independent factors associated with postoperative biochemical failure.

Adjuvant versus early Salvage radiation therapy for prostate cancer with adverse pathological features on radical prostatectomy—Do we finally have an answer?

Background: The presence of adverse pathological features like extraprostatic extension, seminal vesicle involvement, or positive margins at radical prostatectomy incurs a high risk of postoperative recurrence. Currently, adjuvant radiotherapy (ART) is the standard of care in these patients, while early salvage radiotherapy (eSRT) is a potential alternative strategy. Aims: The purpose of this paper is to review the latest evidence comparing outcomes of adjuvant versus early SRT in this clinical scenario. Materials and Methods: A systematic review of Google Scholar, PubMed/Medline, and EMBASE was done to identify relevant studies published in the English language, regarding outcomes of adjuvant radiotherapy and early SRT in post radical prostatectomy patients. Twelve studies, including six randomized trials, four retrospective studies, one systematic review, and one metanalysis were included in the final analysis. Results: We found that initial randomized trials demonstrated better event?free survival with adjuvant radiotherapy when compared to observation alone. However, ART was associated with increased risk of overtreatment and thus increased radiation?related toxicity rates. Conclusion: Preliminary evidence from recently reported RCTs suggests that eSRT may provide equivalent oncological outcomes to ART in prostate cancer patients with adverse pathology on radical prostatectomy while decreasing unnecessary treatment and radiation?related toxicity in a significant proportion of patients. However, the final verdict would be delivered after the long?term metastasis?free survival and overall survival outcomes are available.

Research progress on prostate-specific membrane antigen ligand positron emission tomography imaging of prostate cancer / 生物医学工程学杂志

Prostate cancer is the most common malignant tumor in male urinary system, and the morbidity and mortality rate are increasing year by year. Traditional imaging examinations have some limitations in the diagnosis of prostate cancer, and the advent of molecular imaging probes and imaging technology have provided new ideas for the integration of diagnosis and treatment of prostate cancer. In recent years, prostate-specific membrane antigen (PSMA) has attracted much attention as a target for imaging and treatment of prostate cancer. PSMA ligand positron emission tomography (PET) has important reference value in the diagnosis, initial staging, detection of biochemical recurrence and metastasis, clinical decision-making guidance and efficacy evaluation of prostate cancer. This article briefly reviews the clinical research and application progress on PSMA ligand PET imaging in prostate cancer in recent years, so as to raise the efficiency of clinical applications.

Effect of lymphovascular invasion on biochemical recurrence in patients treated with radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the effect of lymphovascular invasion (LVI) on biochemical recurrence in patients treated with radical prostatectomy (RP).Methods:From June 2012 to November 2020, 403 cases treated with RP in the Second Hospital of Tianjin Medical University were analyzed retrospectively. Median age was 67 (range 47-81) years old. Median prostate specific antigen (PSA) was 18.0 (range 1.9-813.0) ng/ml. All patients received prostate biopsy and were confirmed with prostatic acinar adenocarcinoma according to pathology. The Gleason score of 44 (10.9%) cases were 6, 65 (16.1%) cases were 3+ 4, 62 (15.4%) cases were 4+ 3, and 232 (57.5%) cases were ≥8. 73 (18.1%) patients received neoadjuvant hormonal therapy. RP and pelvic lymph node dissection were carried out in all patients including 10 open surgery, 144 laparoscopic surgery and 249 robot-assisted laparoscopic surgery. The χ 2 test was used to analyze the correlation between LVI and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to summarize time-to-biochemical recurrence end point and compare biochemical recurrence-free survival between LVI positive and negative groups. Univariable and multivariable analyses were performed to test the possible factors of biochemical recurrence with Cox proportional-hazard model. Results:Of all 403 patients treated with RP, the final Gleason score of 68 (16.9%) cases were≤6, 87 (21.6%) cases were 3+ 4, 89 (22.1%) cases were 4+ 3, and 159 (39.5%) cases were≥8. 179 (44.4%) patients had positive surgical margins. The rate of seminal vesicle invasion was 23.6% (95 patients). There were 167 (41.4%) cases with T 1~2 and 236 (58.6%) cases with T 3~4 pathological stage. 39 (9.7%) patients had lymph node metastasis. 62 (15.4%) patients were LVI positive and 341 (84.6%) patients were LVI negative. There were statistically significant differences in biopsy and final Gleason score, pathological stage, rates of seminal vesicle invasion and rates of positive lymph node between LVI positive and negative patients ( P<0.05). 259 (64.3%) patients received adjuvant hormonal therapy and 70 (17.4%) patients received adjuvant hormonal plus radiation therapy. Median follow-up time was 22 (range 6-89) months. 23 (37.1%) occurred biochemical recurrence in LVI positive cases and median biochemical recurrence-free survival was 41 months. Meanwhile, 71 (20.8%) occurred biochemical recurrence in LVI negative cases and median biochemical recurrence-free survival was not reached, significantly longer than LVI positive cases ( P<0.001). Multivariable analysis showed that PSA level, biopsy gleason score, neoadjuvant hormonal therapy, pathological stage, positive surgical margins, seminal vesicle invasion, lymph node metastasis and LVI were significantly associated with prognostic prediction of biochemical recurrence. Conclusions:LVI implies shorter biochemical recurrence-free survival and could be an independent predictor on biochemical recurrence in patients treated with RP.

Risk factor analysis of patients with biochemical recurrence after radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Research progress of salvage lymph node dissection in advanced prostate cancer / 中华泌尿外科杂志

Prostate cancer (PCa) is one of the most common invasive cancers in men. Radical prostatectomy is the gold standard for localized prostate cancer, but the postoperative biochemical recurrence rate can reach 20%-50%. In some cases, salvage lymph node dissections (SLND) seem to improve cancer control and delay systemic treatment. In this article, we review the current state of diagnostic imaging, accurate patient selection criteria, exploration of SLND surgical procedures, as well as the safety and tumor outcomes of SLND. Overall, although there is still a lack of strong prospective evidence to support the role of SLND, advances in preoperative imaging techniques and the widespread use of minimally invasive surgery have led to encouraging tumor outcomes with SLND. However, further large-scale and high quality trials are needed to confirm the effectiveness and safety of SLND.

Neoadjuvant chemo-hormonal therapy for very-high-risk locally advanced prostate cancer: a large cohort retrospective multi-institutional study / 中华泌尿外科杂志

Objective:To investigate the clinical efficacy of neoadjuvant chemo-hormonal therapy(NCHT)followed by radical prostatectomy(RP) plus extended pelvic lymphadenectomy for very-high-risk locally advanced prostate cancer.Methods:The data of 327 cases of very-high-risk locally advanced prostate cancer treated in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, The Second Hospital of Tianjin Medical University, and The Third Affiliated Hospital of Sun Yat-sen University from December 2014 to July 2019 were retrospectively analyzed. Patients were divided into two groups according to treatment regimens: the RP group (direct RP + extended pelvic lymphadenectomy 4-6 weeks after the biopsy of prostate) and the NCHT group (4-6 cycles of NCHT prior to RP). There were 171 cases in RP group and 156 cases in NCHT group, respectively. In the RP group, the median age was 67 (ranging 44-83)years. The median PSA at diagnosis was 27.24 (ranging 4.55-207.00) ng/ml. Patients’numbers of clinical T 2, T 3a, T 3b, T 4 stage were 13, 85, 57, 16, respectively, and clinical N 1, N 0 stage were 33 and 138, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 5, 35, 41, 51, 39, respectively. In the NCHT group, The median age was 67 years, ranging 46-78 years. The median PSA at diagnosis was 72.09(ranging 4.08-722.95)ng/ml. Patients’ numbers of clinical T 2, T 3a, T 3b, T 4 stage were 11, 47, 58, 40, respectively, and clinical N 1, N 0stage were 76 and 80, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 1, 11, 33, 43, 68, respectively. At baseline, the NCHT group showed higher PSA, higher ISUP grade, and more advanced clinical stage at diagnosis( P<0.05). The PSA, pathological down-staging rate, and positive surgical margin rate as well as the biochemical recurrence free survival(bRFS)were compared between the two groups. Results:After radical prostatectomy, compared with the RP group, the NCHT group had a higher proportion of patients achieving PSA<0.2 ng/ml at 6-week postoperative follow-up ( P<0.001), a higher pathologic tumor stage down-staging rate ( P<0.001), a higher ISUP down-grading rate ( P<0.001), and a lower positive surgical margins rate ( P<0.001). In addition, 10.9% of the NCHT group achieved pT 0 or minimal residual disease in postoperative pathology exams. Eighty-three patients (48.5%) in the RP group and 125 patients (80.1%) in the NCHT group achieved undetectable PSA after surgery and entered further analysis for bRFS, which showed NCHT group had significantly longer bRFS (19.46 months vs. 6.35 months). NCHT significantly reduced the risk for biochemical recurrence in locally advanced prostate cancer patients( HR=0.278, 95% CI 0.198-0.390, P<0.001). Such a reduce in risk for biochemical recurrence was seen in all subgroups( P<0.001). Conclusions:NCHT might improve surgical outcomes as well as bRFS in very-high-risk locally advanced prostate cancer patients.

Prognostic factors of salvage radiotherapy after radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Analysis of risk factors for clinical cure and biochemical recurrence in patients after radical prostatectomy / 中华泌尿外科杂志

Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.

Does intraoperative frozen section really predict significant positive surgical margins after robot-assisted laparoscopic prostatectomy? A retrospective study / 亚洲男科学杂志(英文版)

We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9%vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs <4; hazard ratio: 4.386; P = 0.0004) was the only significant predictor of BCR in the PSM cohort. Periurethral frozen sections had a sensitivity of 83.3% and a specificity of 84.2% in detecting PSM with Gleason pattern ≥4. Multivariate analysis showed that membranous urethra length (odds ratio [OR]: 0.79, P = 0.0376) and extracapsular extension of the apex (OR: 4.58, P = 0.0226) on magnetic resonance imaging (MRI) and positive periurethral tissue (OR: 17.85, P < 0.0001) were associated with PSM of the apex. PSM with Gleason pattern ≥4 is significantly predictive of BCR. Intraoperative frozen sections of periurethral tissue can independently predict PSM, whereas sections of the bladder neck and dorsal vein could not. Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes.

MAGI-2 downregulation: a potential predictor of tumor progression and early recurrence in Han Chinese patients with prostate cancer / 亚洲男科学杂志(英文版)

Membrane-associated guanylate kinase (MAGUK) family protein MAGUK invert 2 (MAGI-2) has been demonstrated to be involved in the tumorigenic mechanism of prostate cancer. The objective of this study was to investigate the expression of MAGI-2 at mRNA and protein levels. The prognostic value of MAGI-2 in Han Chinese patients with prostate cancer was also investigated. The expression data of MAGI-2 were assessed through database retrieval, analysis of sequencing data from our group, and tissue immunohistochemistry using digital scoring system (H-score). The clinical, pathological, and follow-up data were collected. The expression of MAGI-2 in prostate tumor tissues and prostate normal tissues was evaluated and compared. MAGI-2 expression was associated with clinical parameters including tumor stage, lymph node status, Gleason score, PSA level, and biochemical recurrence of prostate cancer. The relative expression of MAGI-2 mRNA was lower in the tumor tissue in The Cancer Genome Atlas (TCGA) database and sequencing data (P < 0.001). There was no difference in MAGI-2 protein expression between tumor and normal tissues in tissue microarray (TMA) results. MAGI-2 expression was associated with pathological tumor stage (P = 0.02), Gleason score (P = 0.05), and preoperation prostate-specific antigen (PSA; P = 0.04). A positive correlation was identified between MAGI-2 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressions through the analysis of TCGA and TMA data (P < 0.0001). Patients with higher MAGI-2 expression had longer biochemical recurrence-free survival in the univariate analysis (P = 0.005), which indicates an optimal prognostic value of MAGI-2 in Han Chinese patients with prostate cancer. In conclusion, MAGI-2 expression gradually decreases with tumor progression, and can be used as a predictor of tumor recurrence in Chinese patients.

Transurethral resection of the prostate is an independent risk factor for biochemical recurrence after radical prostatectomy for prostate cancer / 亚洲男科学杂志(英文版)

Biochemical recurrence (BCR) is important for measuring the oncological outcomes of patients who undergo radical prostatectomy (RP). Whether transurethral resection of the prostate (TURP) has negative postoperative effects on oncological outcomes remains controversial. The primary aim of our retrospective study was to determine whether a history of TURP could affect the postoperative BCR rate. We retrospectively reviewed patients with prostate cancer (PCa) who had undergone RP between January 2009 and October 2017. Clinical data on age, prostate volume, serum prostate-specific antigen levels (PSA), biopsy Gleason score (GS), metastasis stage (TNM), D'Amico classification, and American Society of Anesthesiologists (ASA) classification were collected. Statistical analyses including Cox proportional hazard models and sensitivity analyses which included propensity score matching, were performed, and the inverse-probability-of-treatment-weighted estimator and standardized mortality ratio-weighted estimator were determined. We included 1083 patients, of which 118 had a history of TURP. Before matching, the non-TURP group differed from the TURP group with respect to GS (P= 0.047), prostate volume (mean: 45.19 vs 36.00 ml, P < 0.001), and PSA level (mean: 29.41 vs 15.11 ng ml-1, P= 0.001). After adjusting for age, PSA level, T stage, N stage, M stage, and GS, the TURP group showed higher risk of BCR (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.13-3.94, P= 0.004). After matching (ratio 1:4), patients who underwent TURP were still more likely to develop BCR according to the adjusted propensity score (HR: 2.00, 95% CI: 1.05-3.79, P= 0.034). Among patients with PCa, those with a history of TURP were more likely to develop BCR after RP.

Salvage lymph node dissection for metastatic castration resistant prostate adenocarcinoma

@#Presented here is a 66 year old male who is a known case of prostate adenocarcinoma gleason score 9 (4+5) and who underwent open radical retropubic prostatectomy with bilateral pelvic lymph node dissection, followed by 45 cycles of radiation therapy with continous androgen deprivation therapy. Afer completion of radication therapy, Choline PET CT was done which revealed enlarged paracaval, aortocaval and paraaortic lymph nodes. The patient then underwent exploratory laparotomy, retroperitoneal lymph node dissection which found four out of twenty five lymph nodes removed that were positive for tumor metastases. There was a significant drop in the prostate specific antigen level two months post-surgery, from 7.43 to 1.54. Androgen deprivation therapy was still continued post-operatively.

Correlation of tumor location and biochemical recurrence in localized and locally-advanced prostate cancer in post-robotic radical prostatectomy patients

OBJECTIVE@#This study aims to determine the tumor location of prostate adenocarcinoma in patientswho underwent Robotic Radical Prostatectomy (RRP) for localized and locally-advanced prostatecancer and the correlation of the tumor location with the incidence of biochemical recurrence.@*PATIENTS AND METHODS@#The authors reviewed the patient database of a single Urological Oncologistfrom January 2015 to April 2017 for patients who underwent RRP for localized or locally-advancedprostate cancer. They also reviewed the histopathologic report of the prostatectomy specimens todetermine pathologic T-stage, prostate volume, and post-operative Gleason score. The histopathologicexamination of specimens was interpreted by a single Urological Pathologist based on the 2014International Society of Urological Pathology Gleason Scoring System. Eligible patients were thendivided into three groups: those with pure anterior tumor location, pure posterior tumor location,and mixed tumor location. Presence of positive surgical margins, mean follow-up period, andbiochemical recurrence were determined for these groups. Patient demographic data were analyzedusing test of proportions. Correlation of tumor location with biochemical recurrence was derivedusing Pearson chi-square test.@*RESULTS@#Of the 113 patients included in the study, 63 (55.8%) were clinically-staged T2 patients while27 (23.9%) and 23 (20.3%) were clinical stage T1 and T3, respectively. On pre-operative prostatebiopsy, 27 (23.9%) patients had a Gleason score of 8-10. Thirty-eight (33.6%) and 30 (26.6%) had aGleason score of 6 (3+3) or 7 (3+4), respectively Average prostate volume was 42.8 grams. Ninety-five (84.1%) of the patients had mixed tumor location, 11 (11.6%) had pure posterior tumor location,and only 7 (6.2%) had pure anterior tumor location. In those with pure anterior or posterior tumorlocations, majority were low-grade prostate cancers (Gleason 6(3+3) and Gleason 7(3+4)) whilethose with mixed tumor location had low to high-grade prostate cancers (Gleason 7 (3+4) and Gleason7 (4+3.)) Majority of the patients had pathologic T2c and T3a tumors across all groups. Positivesurgical margins were present in 31% of those with mixed tumor location and only 0.9% in those withpure anterior or posterior tumor location, respectively. Only 10 patients from the population hadbiochemical recurrence, 9 of which had mixed tumor location while 1 had pure posterior tumorlocation. Pearson chi-square test shows no significant relationship between tumor location andbiochemical recurrence at 95% CI (p= regional involvement 0.695.) Furthermore, there is a very weak positive correlation (R=0.069) between tumor location and biochemical recurrence.@*CONCLUSION@#Majority of patients who underwent RRP have mixed tumor location. There is poorcorrelation between prostate cancer tumor location and biochemical recurrence.

Multivariate analysis of factors affecting biochemical recurrence after radical prostatectomy

OBJECTIVE@#This study aims to evaluate the effects on biochemical recurrence (BCR) of the followingproposed prognostic factors after radical prostatectomy (RP): patients' clinical T stage, Gleason gradegroup (GG) of RP specimen, technique of operation used (open RP vs. robot-assisted laparoscopicRP), presence of positive surgical margin (PSM), length of PSM, GG at PSM, extraprostatic extension(EPE) at PSM, and presence of detectable PSA at 4-6 weeks after RP. It also aims to identify whichamong the aforementioned variables are independent predictors of risk for BCR.@*PATIENTS AND METHODS@#This is a retrospective study. Included in the study were patients who underwentRP (Open and Robot-assisted Laparoscopic technique) at two tertiary hospital branches of an academicmedical center from April 2009 to December 2015 with histopathology reports read by a singleurologic pathologist and with complete follow- up for at least one year. Excluded were those whounderwent RP but without complete follow- up. Using Pearson chi-square and z-test with level ofsignificance set at 0.05, the clinicopathologic variables including: patients clinical stage, GG of RPspecimen, length of PSM, GG at positive margins, presence of EPE at positive margins, and presenceof detectable PSA after the surgery were assessed in order to know which among these factors werepredictive of BCR. Multinomial regression analysis was also used to identify which among the variableswere independent predictors of risk for BCR.@*RESULTS@#A total of 165 patients underwent RP from April 2009 to December 2015, among which 72patients were eligible for inclusion in the final analysis. Clinical T2 stage was found to be a predictorof BCR with odds ratio of 13.000 (95%CI: 3.705 - 45.620; p < 0.001) as compared to stage T1. GGof final histopathology report of prostatectomy specimen was found to be a predictor of BCR, asthose with grade groups 4 and 5 had significantly increased risk of BCR with odds ratio of 70.778(95%CI: 8.207 - 610.426; p < 0.001) as compared to those with grade groups 1 to 3. Patients withpositive margins had increased risk of BCR, with odds ratio of 13.458 (95%CI: 13.472 - 52.171; p <0.001) compared to those with negative margins. GG at the PSM was found to be a predictor of BCR,with a grade grouping of 4 or 5 at the positive margin predicting BCR with odds ratio of 20.625(95%CI: 2.241 - 189.847; p = 0.008) as compared to grade grouping of 1 or 2 at the margin. DetectablePSA after RP was found to be a predictor of BCR, with odds ratio of 115.000 (95%CI: 19.457 -679.712; p < 0.001) as compared to undetectable PSA after RP. Technique of RP (p = 0.177), measuredlength of PSM (p = 0.713), and EPE at PSM (p = 0.146) were not found to predict BCR. Furthermore,clinical T stage (p = 0.007) and detectable PSA after RP (p < 0.001) were found to be independentpredictors of BCR among the risk factors examined.@*CONCLUSION@#Of the independent variables examined, clinical T stage, GG of RP specimen, presenceof PSM, GG at positive margins, and detectable PSA were found to be significant predictors of BCR. Technique of RP, measured length of PSM, and EPE at PSM were not found to predict BCR.Furthermore, multivariate analysis showed that only clinical T stage and detectable PSA after RPwere independent predictors of BCR. Attentive assessment of these predictors in the preoperativeperiod should aid the urologist in clinical decision-making and in advising patients regarding theirprognosis.

Correlation of metallothionein-2A, E-cadherin and cyclin E with biochemical recurrence in prostate cancer / 肿瘤研究与临床

Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5％ (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8％(8/54), 38.7％(24/62) and 58.3％ (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95％CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95％CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95％CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95％ CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.

Identification of seven long noncoding RNAs signature for prediction of biochemical recurrence in prostate cancer / 亚洲男科学杂志(英文版)

Accumulating evidence suggested that long noncoding RNAs (lncRNAs) possess a potential role in prostate cancer (PCa) diagnosis and prognosis. Rapid biochemical recurrence (BCR) is considered as a sign for clinical recurrence metastasis and PCa-specific mortality. Hence, the aim of the present study was to identify a lncRNA signature that can predict BCR of PCa accurately. Bioinformatics analysis, Kaplan-Meier analyses, Cox regression analyses, and Gene Set Enrichment Analysis (GSEA) were performed in a publicly available database with 499 PCa tissues and 52 matched normal tissues. A signature was identified. All these lncRNAs were differentially expressed between tumor and normal tissues and differentially expressed between high Gleason score and low Gleason score tissues. Furthermore, we developed a seven lncRNAs signature that can predict PCa BCR. Patients classified into low-risk group showed better BCR survival significantly than the patients in the high-risk group (hazard ratio = 0.32, 95% CI: 0.20-0.52, concordance index = 0.63). The area under the curve was 0.68 for BCR. The signature also had good discrimination for BCR in men with Gleason 7 PCa. In conclusion, our results suggest that the seven lncRNAs signature is a new biomarker of BCR and high risk in PCa. In addition, the individual lncRNA warrants further study to uncover the associated mechanisms of PCa progression and the signature could be used to design direct clinical trials for adjuvant therapy.

Clinical characteristics and treatment strategies of prostate mucinous adenocarcinoma: the multicenter summary of 36 cases / 中华泌尿外科杂志

Objective To review the clinical characteristics of prostate mucinous adenocarcinoma cases and update literatures,and recommend the corresponding clinical treatment strategy.Methods From October 2010 to March 2018,36 cases of prostate mucinous adenocarcinoma were involved from 5 urinary centers in China,including 9 cases from Shanghai Changhai Hospital,4 cases from Wuhan Tongji Hospital,13 cases from Shanghai Renji Hospitals,8 cases from the First Affiliated Hospital of Nanjing Medical University,and 2 cases from Sichuan West China Hospitals.The patients' age were (66.8 ±7.2) years (53-83 years) and the median PSA was 22.89 ng/ ml (2.67-1786 ng/ ml).Prostate biopsy confirmed Gleason score 3 + 3 points in 6 cases,3 + 4 points in 9 cases,4 + 3 points in 5 cases,8 points in 11 cases,and 9 to 10 points in 5 cases.According to D'Amico risk stratification,2 patients were in the low-risk group,9 in the intermediate-risk group,and 25 in the high-risk group.Eight cases underwent radical retroperitoneal prostatectomy,13 cases underwent laparoscopic radical prostatectomy,and 12 cases underwent robotic laparoscopic radical prostatectomy.Twenty-three cases underwent pelvic lymphadenectomy,including 12 cases of bilateral obturator lymph node dissection,and 11 cases of bilateral obturator + intraorbital + para-vascular para-aortic lymphadenectomy.Results All 36 operations were completed successfully.Twenty-three cases underwent pelvic lymphadenectomy,including 12 of bilateral obturator lymph node dissection,and 11 of bilateral obturator,intraorbital,and para-aortic lymphadenectomy.Pathological examination showed 9 cases of prostate mucinous adenocarcinoma,26 cases of mucinous adenocarcinoma with acinar adenocarcinoma,and 1 case of mucinous adenocarcinoma with neuroendocrine and immunohistochemical positive of MUC2 (+).Among 33 cases undergoing radical surgery,the pathological stage of ≤T2b in 12 cases (36.3％),T2c in 7 cases (21.2％),T3a in 7 cases (21.2％),T3b in 6 cases (18.2％),and T4 in 1 case (3.0％).Four cases had positive pelvic lymph nodes and 9 cases had positive margin.The median follow-up period was 26 months (6-48 months).The biochemical recurrence occurred in 6 patients one year after surgery,including 3 cases in the intermediaterisk group and 3 cases in the high-risk group.Six cases with postoperative biochemical recurrence and 19 cases with PSA ＞ 0.2 ng/ml after radical or palliative resection underwent adjuvant androgen deprivation therapy(ADT),no postoperative adjuvant radiotherapy or chemotherapy was administered,and 4 cases progressed to castration-resistant prostate cancer.Four cases with CRPC were in the high-risk group and had underwent radical surgery,and the median period progressed to CRPC was 26 months(3-37months)with 2 cases of death.However,there was no significant difference in the rate of biochemical recurrence and the incidence of CRPC in the low-risk group,the intermediate-risk group and the high-risk group.In addition,2 cases had metastases,with pelvic MRI presenting pelvic multiple nodular mass in one case which was consistent with recurrence and metastasis at the 5th month after radical surgery,and pathological examination presenting the mucinous adenocarcinoma being neurosecretory in another case and mestastasis being detected on glans at the 3rd months after radical surgery.The recovery rate of urinary continience at 6 and 12 months after radical surgery was 86.2％ (31/36) and 89.7％ (32/36) respectively.Conclusions Prostate mucinous adenocarcinoma is a variant of acinar adenocarcinoma.This study clarifies prostate mucinous adenocarcinoma of Chinese patients with high Gleason scores,advanced pathological stage,variant in prognosis,and prone to recurrence and metastasis.For treatment strategy,the low-risk and intermediate-risk mucinous adenocarcinoma is recommended undergoing radical surgery,and the prognosis maybe good.High-risk mucinous adenocarcinoma could treated with radical surgery or palliative surgery with adjuvant ADT,and most high-risk patients can benefite,with a small number of poor prognosis.

The correlation analysis of positive surgical margin and biochemical recurrence after robot-assisted laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP).Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected.Age was (67.5 ±6.9) years old;median body mass index (BMI),preoperative PSA,prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2),15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively.The group of surgical margin was divided into negative surgical margin,apex-only PSM,base-only PSM as well as apex and base PSM.Characteristics between patients stratified by surgical margin or BCR were compared using x2 test.The influencing factors of PSM were analyzed by logistic regression.Cox regression was used for the analysis of predictive factors of BCR.Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin.Results Of all the 190 enrolled patients,total PSM rate was 24.7％ (47/190),apex-only PSM rate was 13.2 ％ (25/190),base-only PSM rate was 5.8％ (11/190),apex and base PSM rate was 5.8 ％ (11/190).Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P =0.048) and pathological stage (P =0.004).The median follow-up period was 7.3 months (0.9-26.6months) and BCR happened in 19.5％ (37/190) patients.The rates of BCR were 15.4％ (22/143),16.0％ (4/25),27.3％ (3/11) and 72.7％ (8/11) in the patients with negative surgical margin,apexonly PSM,base-only PSM and both apex and base PSM respectively.Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P ＜0.001) or patients with apex-only PSM(P =0.002).Cox analysis indicated that higher preoperative PSA (P =0.040),higher pathological stage (P =0.041) and higher pathological Gleason score (P =0.004) were the independent predictors of BCR.PSM was not a predictive factor of BCR (P =0.257).Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM.Higher preoperative PSA,higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR.PSM may not be a predictive factor of BCR.The relationship between PSM and BCR needs further study.