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1.
BMC Urol ; 24(1): 58, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38475808

ABSTRACT

PURPOSE: To analyze surgical and oncologic outcomes of patients undergoing open partial nephrectomy (OPN) versus laparoscopic partial nephrectomy (LPN) for treatment of renal cell carcinoma (RCC). METHODS: We retrospectively investigated our institutional RCC database for patients who underwent PN for RCC from 1997 to 2018. Decision for technique was at the discretion of the operating urologist, following practice patterns and training history. Outcomes analyzed included pre/peri/post-operative parameters, pathologic outcomes, and disease recurrence rates. RESULTS: 1088 patients underwent PN from 1997 to 2018. After exclusionary criteria, 631 patients who underwent 647 unique PNs for a total of 162 OPN and 485 LPN remained. Baseline, pre-op, and pathologic characteristics were not statistically different. Surgical time was lower in laparoscopic cases [185 vs. 205 min] (p = 0.013). Margin involvement was not statistically different; LPN had lower estimated blood loss (EBL) [150 vs. 250 mL] (p < 0.001) and longer ischemia time [21 vs. 19 min] (p = 0.005). LPN had shorter length of stay [2 vs. 4 days] (p < 0.001), fewer overall complications (p < 0.001), and no significant difference in high-grade complications [2.89 vs. 4.32%] (p = 0.379). Fewer LPN patients developed metastases [1.65 vs. 4.94%] (p = 0.0499). Local recurrence rates were not statistically different [1.24 vs. 3.09%] (p = 0.193). Renal function was equivalent between cohorts post-operatively. CONCLUSION: Long-term oncologic outcomes were not significantly different between LPN versus OPN, with no statistical difference in patient and tumor characteristics. LPN was associated with lower EBL, shorter length of stay, and lower overall complication risk. Renal function was not significantly different between cohorts.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Laparoscopy , Humans , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Retrospective Studies , Treatment Outcome , Laparoscopy/methods , Nephrectomy/methods
2.
Asian J Urol ; 10(3): 317-328, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37538158

ABSTRACT

Objective: To investigate the association of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) with clinicopathological features and long-term oncological prognosis for the development of a potential management strategy. Methods: A systematic literature search was performed using PubMed and Web of Science up to June 2021 to identify the eligible studies focusing on understanding the impact of persistent PSA in patients who underwent RP for localized prostate cancer. Meta-analyses were performed on parameters with available information. Results: A total of 32 RP studies were identified, of which 11 included 26 719 patients with consecutive cohorts and the remaining 21 comprised 24 177 patients with cohorts carrying specific restrictions. Of the 11 studies with consecutive cohorts, the incidence of persistent PSA varied between 3.1% and 34.6% with a median of 11.0%. Meta-analyses revealed patients with persistent PSA consistently showed unfavorable clinicopathological features and a more than 3.5-fold risk of poorer biochemical recurrence, metastasis, and prostate cancer-specific mortality prognosis independently, when compared to patients with undetectable PSA. Similarly, cases with persistent PSA in different specific patient cohorts with a higher risk of prostate cancer also showed a trend of worse outcomes. Conclusion: We found that the frequency of persistent PSA was about 11.0% in consecutive RP cohorts. Persistent PSA was significantly associated with unfavorable clinicopathological characteristics and worse oncological outcomes. Patients with persistent PSA after RP may benefit from early salvage treatment to delay or prevent biochemical recurrence, improving oncological outcomes for these patients. Further prospective randomized controlled trials are warranted to understand optimal systemic therapy in these patients.

3.
Urol Oncol ; 41(9): 387.e9-387.e16, 2023 09.
Article in English | MEDLINE | ID: mdl-37208229

ABSTRACT

OBJECTIVE: Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity. METHODS: We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34-0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment. CONCLUSIONS: A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS.


Subject(s)
Disease Progression , Prostatic Neoplasms , Watchful Waiting , Biopsy , Prostatic Neoplasms/pathology , Humans , Male , Progression-Free Survival , Cohort Studies , Middle Aged , Aged , Neoplasm Grading , Prostate-Specific Antigen/blood
4.
Urol Clin North Am ; 50(2): 261-284, 2023 May.
Article in English | MEDLINE | ID: mdl-36948671

ABSTRACT

Most kidney cancers are primary renal cell carcinomas (RCC) of clear cell histology. RCC is unique in its ability to invade into contiguous veins - a phenomenon terms venous tumor thrombus. Surgical resection is indicated for most patients with RCC and an inferior vena cava (IVC) thrombus in the absence of metastatic disease. Resection also has an important role in selected patients with metastatic disease. In this review, we discuss the comprehensive management of the patient with RCC with IVC tumor thrombus, emphasizing a multidisciplinary approach to the surgical techniques and perioperative management.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Thrombosis , Venous Thrombosis , Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Vena Cava, Inferior/surgery , Thrombectomy/methods , Retrospective Studies , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Venous Thrombosis/etiology , Venous Thrombosis/surgery , Venous Thrombosis/pathology , Thrombosis/pathology , Thrombosis/surgery , Nephrectomy/methods
6.
J Urol ; 209(6): 1112-1119, 2023 06.
Article in English | MEDLINE | ID: mdl-36951811

ABSTRACT

PURPOSE: Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. MATERIALS AND METHODS: Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. RESULTS: Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. CONCLUSIONS: An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.


Subject(s)
Prostatic Neoplasms , Watchful Waiting , Male , Humans , Watchful Waiting/methods , Retrospective Studies , Prostatic Neoplasms/pathology , Prostatectomy , Risk Factors , Neoplasm Grading , Prostate-Specific Antigen
7.
Asian J Urol ; 10(1): 9-18, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36721688

ABSTRACT

Objective: Guidelines for muscle-invasive bladder cancer (MIBC) recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described. Methods: Using the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer. We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan-Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival. Results: Of 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than Caucasian. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status. Conclusion: Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment.

8.
Urol Oncol ; 40(2): 59.e1-59.e5, 2022 02.
Article in English | MEDLINE | ID: mdl-34544650

ABSTRACT

PURPOSE: Gleason grade (GG) on prostate biopsy is important for risk stratification and clinical decision making. Multiparametric MRI (mpMRI) improved detection of clinically significant disease and some studies suggest that MRI-fusion biopsy combined with systematic biopsy results in fewer upgrades on final surgical pathology. However, the downgrade rate is unclear and there is controversy in the literature. The objectives of this study are to assess the concordance of combination biopsy with final surgical pathology, and furthermore, to specifically determine downgrade rates. MATERIALS AND METHODS: In our institutional mpMRI-ultrasound fusion biopsy database, 173 underwent targeted and systematic biopsy followed by radical prostatectomy (RP). GG on targeted, systematic and combination (targeted and systematic) biopsy were compared with GG on RP. Concordance rates between biopsy types were compared with the McNemar test. Proportion of GG upgrade or downgrade at the time of RP was also evaluated. RESULTS: Surgical pathology was concordant with 44.5% of systematic biopsies, 46.8% of targeted biopsies, and 56.7% of combination biopsies. Combination biopsy significantly overestimated the final GG on RP compared to systematic biopsy (16.8% vs. 8.7% RR 1.93, 95% CI 1.36-2.75, P < 0.001). Downgrade rate from unfavorable to favorable intermediate-risk disease was 46.2%, and from high-risk to intermediate-risk disease was 45.1%. CONCLUSIONS: Combination (targeted and systematic) biopsy is associated with the highest concordance rate between biopsy and RP pathology when compared with systematic or targeted biopsy alone. However, targeting MRI lesions and therefore the higher risk components, may at times overestimate the final surgical pathology which can result in overtreatment of what may truly be less aggressive disease.


Subject(s)
Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Humans , Male , Neoplasm Grading , Prostate/pathology
9.
J Urol ; 206(1): 29-36, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33617327

ABSTRACT

PURPOSE: Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. MATERIALS AND METHODS: We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013. Patients were grouped as salvage cystectomy post-trimodality therapy, primary cystectomy or primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Early (≤90 days) and late (>90 days) complications were compared. Disease-specific survival and overall survival were calculated using a Cox regression model, and adjusted survival curves were generated. RESULTS: The median followup from the time of cystectomy was 65.5 months. There was no difference in intraoperative and early complications between the groups. The detection of late complications was higher in salvage cystectomy post-trimodality therapy compared to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy (p=0.03). In multivariable Cox regression analysis, salvage cystectomy post-trimodality therapy was associated with a higher incidence of any late (HR 2.3, p=0.02) and major late complications (HR 2.1, p <0.05). There was no difference in disease-specific survival (p=0.8) or overall survival (p=0.9) between the groups. CONCLUSIONS: Salvage cystectomy post-trimodality therapy for intravesical recurrence post-trimodality therapy has an intraoperative and early complication rate comparable to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Salvage cystectomy post-trimodality therapy is associated with a higher risk of overall and major late complications than primary cystectomy. The disease-specific survival and overall survival of patients who require salvage cystectomy post-trimodality therapy are comparable to both groups.


Subject(s)
Cystectomy , Neoplasm Recurrence, Local/surgery , Postoperative Complications/epidemiology , Urinary Bladder Neoplasms/surgery , Aged , Combined Modality Therapy , Cystectomy/methods , Female , Humans , Male , Retrospective Studies , Salvage Therapy , Treatment Outcome , Urinary Bladder Neoplasms/therapy
10.
Oncogene ; 40(1): 46-54, 2021 01.
Article in English | MEDLINE | ID: mdl-33051598

ABSTRACT

Chronic BK polyomavirus (BKPyV) infection is recognized as a potential oncogenic factor of urothelial carcinoma (UC) in renal transplant recipients. Recent studies have reported a positive correlation among BKPyV integration, persistent overexpression of viral large T antigen (TAg), and malignancy, yet little is known about the specific integration mechanisms and the impacts of viral integration. Here, we performed whole-genome sequencing (WGS) and viral capture-based sequencing on high-grade immunohistochemically TAg-positive UCs in two renal transplant recipients. A total of 181 integration sites, including the three found by WGS, were identified by viral capture-based sequencing, indicating its enhanced sensitivity and ability in identifying low-read integration sites in subpopulations of the tumor cells. The microhomologies between human and BKPyV genomes were significantly enriched in the flanking regions of 84.5% the integration sites, with a median length of 7 bp. Notably, 75 human genes formed fusion sequences due to viral insertional integration. Among them, the expression of 15 genes were statistically associated with UC based on GEO2R expression analysis. Our results indicated a multisite and multifragment linear integration pattern and a potential microhomology or nonhomologous end joining integration mechanism at the single-nucleotide level. We put forward a potential selection mechanism driven by immunity and centered on viral integration in the carcinogenesis of BKPyV.


Subject(s)
BK Virus/physiology , Gene Regulatory Networks , Kidney Transplantation/adverse effects , Polyomavirus Infections/genetics , Tumor Virus Infections/genetics , Urinary Bladder Neoplasms/virology , Whole Genome Sequencing/methods , Adult , Aged , Antigens, Viral, Tumor/metabolism , BK Virus/genetics , Chromosome Breakage , Female , Genome, Human , Genome, Viral , Humans , Kidney Failure, Chronic/therapy , Polyomavirus Infections/virology , Tumor Virus Infections/virology , Urinary Bladder Neoplasms/genetics , Virus Integration
11.
Am J Clin Oncol ; 43(12): 872-879, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33002923

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer. PATIENTS AND METHODS: We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed. CONCLUSIONS: In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.


Subject(s)
Margins of Excision , Prostatectomy/methods , Prostatic Neoplasms/surgery , Aged , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Treatment Outcome
12.
Scand J Urol ; 54(6): 475-480, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32930036

ABSTRACT

OBJECTIVES: To identify the potential indicators for higher-risk disease and poor outcome in younger prostate cancer (PCa) patients (age ≤ 50) who had undergone radical prostatectomy (RP) in the prostate-specific antigen (PSA) era. MATERIALS AND METHODS: A total of 186 PCa cases of age ≤ 50 who underwent RP between 2003 and 2010 at our center were included for study. High-risk disease after RP was defined as cases with pre-PSA ≥ 20 ng/ml and/or Gleason score (GS) ≥ 4 + 3 and/or pT stage ≥ 3. The poor outcome group was defined as cases with biochemical recurrence (BCR) and/or metastasis (Mets) and/or all-cause death. Multivariate logistic regression models were performed to identify independent risk factors for both high-risk disease and poor outcome. RESULTS: Among 186 younger PCa patients aged ≤ 50, 36 cases (19.5%) had high-risk disease and 24 cases (12.9%) had poor outcome. The presence of biopsy perineural invasion (BxPNI) was significantly associated with high-risk disease and showed a trend to correlate with worse outcome in univariate analysis. On multivariate logistic regression analysis, BxPNI was shown to be a significant independent risk factor with covariate of D'Amico for poor outcome (p = 0.047) and an independent risk factor with covariate of BxGPC for high-risk PCa excepting the variables to define high-risk disease (p = 0.013). Prognostically, cases with BxPNI showed a poor BCR-free survival in univariate analysis but did not reach significance (p = 0.063). CONCLUSION: Our results show that BxPNI could be considered as a risk classification factor to identify the best candidates among younger PCa patients for further treatment and may also be used for developing active surveillance (AS) selection criteria for younger PCa patients.


Subject(s)
Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Adult , Age Factors , Biopsy , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prostate/innervation , Retrospective Studies , Risk Factors
13.
Cancer Med ; 9(18): 6473-6484, 2020 09.
Article in English | MEDLINE | ID: mdl-32697048

ABSTRACT

OBJECTIVES: With the rapid increase in younger age prostate cancer (PCa) patients, the impact of younger age on decision-making for PCa treatment needs to be revaluated in the new era. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, EMBASE, and Web of Science up to October 2019 to identify the eligible radical prostatectomy (RP) studies focusing on understanding the impact of age on clinicopathological features and oncological prognosis in patients with localized PCa in PSA era. Meta-analyses were conducted using available hazard ratios (HRs) from both univariate and multivariate analyses. RESULTS: Twenty-six studies including 391 068 patients with RP treatments from the PSA era were included. Of these studies, age of 50 years old (age50) is the most commonly used cut-off age to separate the younger patient group (including either age < 50 or age ≤ 50) from the older patient group. In these studies, the incidence of younger patients varied between 2.6% and 16.6% with a median of 8.3%. Younger patients consistently showed more favorable clinicopathological features correlated with better BCR prognosis. Meta-analyses showed a 1.38-fold improved BCR survival of younger patients in multivariate analysis. Among the high-risk PCa patients, younger age was independently associated with worse oncological outcomes in multivariate analyses. CONCLUSION: In this study, we found younger age correlated with favorable clinicopathological characteristics and better BCR prognosis in low- to intermediate-risk patients. In high-risk group patients, younger patients often showed significantly worse oncological outcomes. Our study results suggest that age 50 could be used as a practical cut-off age to separate younger age patients from older age PCa patients.


Subject(s)
Kallikreins/blood , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/surgery , Age of Onset , Aged , Aged, 80 and over , Clinical Decision-Making , Humans , Male , Middle Aged , Predictive Value of Tests , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/mortality , Risk Assessment , Risk Factors , Treatment Outcome
14.
Hum Pathol ; 104: 96-104, 2020 10.
Article in English | MEDLINE | ID: mdl-32673683

ABSTRACT

Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI-) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.


Subject(s)
Neoplasm Recurrence, Local , Peripheral Nerves/pathology , Prostatectomy , Prostatic Neoplasms/surgery , Aged , Databases, Factual , Disease-Free Survival , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prostatectomy/adverse effects , Prostatectomy/mortality , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
15.
Oncogene ; 39(35): 5734-5742, 2020 08.
Article in English | MEDLINE | ID: mdl-32724161

ABSTRACT

BK polyomavirus (BKPyV)-associated cancer after transplantation has gained increasing attention. However, the role of BKPyV integration on oncogenesis is still unclear. In this study, next-generation virome capture sequencing of primary and metastatic tumors were performed in three patients with BKPyV-associated urothelial carcinoma after renal transplantation. As a result, a total of 332 viral integration sites were identified in the six tumors. Integration of BKPyV in both primary and metastatic tumors followed the mechanism of microhomology-mediated end joining mostly, since microhomologies between human and BKPyV genomes were significantly enriched in flanking regions of 84% of the integration sites. Viral DNA breakpoints were nonrandom and tended to assemble in large T gene, small T gene and viral protein 2 gene. There were three, one and one consensus integration sites between the primary and metastatic tumors, which affected LINC01924, eIF3c, and NEIL2 genes in the three cases respectively. Thus, we concluded that integration of BKPyV was a continuous process occurring in both primary and metastatic tumors, generating heterogenous tumor cell populations. Through this ongoing process, certain cell populations might have gained growth advantage or metastatic potential, as a result of viral integration either affecting the cellular genes where the viral DNA integrated to or altering the expression or function of the viral genes.


Subject(s)
BK Virus/genetics , High-Throughput Nucleotide Sequencing/methods , Polyomavirus Infections/virology , Tumor Virus Infections/genetics , Urologic Neoplasms/genetics , Aged , Female , Humans , Male , Middle Aged , Polyomavirus Infections/pathology , Tumor Virus Infections/pathology , Urologic Neoplasms/pathology , Virus Integration
16.
17.
Scand J Urol ; 53(5): 287-294, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31401922

ABSTRACT

Objectives: To investigate the association between biopsy perineural invasion (PNI) and oncological outcomes of prostate cancer (PCa) after radical prostatectomy (RP).Materials and methods: A systematic literature search was performed using PubMed, EMBASE and Web of Science up to December 2018 to identify the eligible studies that included localized PCa patients who underwent biopsy and subsequently RP as well as follow-up information. Meta-analyses were conducted using available hazard ratios (HRs) of biopsy PNI from both univariate and multivariate analyses.Results: Eighteen studies including 14,855 patients with treatment follow-up information were included in the current systematic review. The rate of biopsy PNI varied between 7.0% and 33.0%. Seven out of the 18 studies that demonstrated biopsy PNI were associated with adverse pathologic features. Thirteen out of the 18 studies showed biopsy PNI correlated significantly with higher rates of biochemical recurrence (BCR)/cancer progression status or worse prognostic outcomes. With pooled data based on four studies with available univariate analysis results and four studies with multivariate analysis, statistically significant associations were found between biopsy PNI and BCR with univariate analysis (HR = 2.05; 95% CI = 1.57-2.68; p < 0.001) and with multivariate analysis (HR = 1.57; 95% CI = 1.28-1.93; p < 0.001).Conclusion: Evidence from the included observational studies indicated that biopsy PNI was not only correlated with adverse pathologic characteristics but also with worse BCR prognosis of local PCa after RP. The status of biopsy PNI could serve as a promising risk-stratification factor to help the decision-making process, considering active surveillance (AS) or further treatment for PCa patients.


Subject(s)
Prostate/innervation , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Biopsy , Humans , Male , Neoplasm Invasiveness/pathology , Prostatectomy/methods
18.
Eur Urol Oncol ; 2(4): 365-378, 2019 07.
Article in English | MEDLINE | ID: mdl-31109902

ABSTRACT

CONTEXT: The current role of cytoreductive nephrectomy (CN) is controversial. OBJECTIVE: Review of the available evidence about criteria defining CN optimal candidates. EVIDENCE ACQUISITION: Collaborative critical narrative review of the literature focusing on CN oncological outcomes, perioperative morbidity, eligibility criteria, presurgical systemic therapy, and surgical factors. EVIDENCE SYNTHESIS: In contrast to observational studies, the Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) trial demonstrated noninferiority of targeted therapy alone relative to CN with targeted therapy. CN is associated with a significant risk of perioperative mortality (0-13%) and major complications (3-36%). Metastatic burden, haematological parameters, performance status, sarcopenia, and genetic mutations have been proposed as CN eligibility criteria. Comprehensive models including local and systemic factors are recommended. The Immediate Surgery or Surgery after sunitinib Malate In Treating Patients with Kidney Cancer (SURTIME) trial reported similar progression-free rate after immediate or deferred CN, and suggests that presurgical systemic therapy can identify candidates for CN, avoiding unnecessary surgery in nonresponders without increasing the risk of perioperative complications. Minimally invasive and nephron-sparing CNs are established surgical strategies in selected patients. CONCLUSIONS: No benefit of upfront CN is observed for intermediate- and poor-risk patients who require systemic therapy in randomised controlled trials, and systemic therapy deserves priority over CN in patients with metastatic renal cell carcinoma. These findings are not applicable to all patients with metastatic kidney cancer. CN has a role in favourable cases not requiring immediate systemic therapy or in symptomatic patients. Individual patient selection to identify those patients who might profit the most from CN is critical; however, clinical decision making should be based on comprehensive models. Presurgical systemic therapy is a promising option to avoid unnecessary CN, which is associated with major morbidity. PATIENT SUMMARY: Consideration for systemic therapy deserves priority over cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. In patients eligible for systemic therapy, CN does not offer a survival benefit. The indications for CN should be evaluated on an individual basis. Risk scores and response to presurgical systemic therapy can be used for subsequent decision making.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Carcinoma, Renal Cell/drug therapy , Cytoreduction Surgical Procedures , Humans , Kidney Neoplasms/drug therapy , Nephrectomy , Treatment Outcome
19.
J Urol ; 202(5): 944-951, 2019 11.
Article in English | MEDLINE | ID: mdl-31144593

ABSTRACT

PURPOSE: There exists a growing debate as to whether multiparametric magnetic resonance imaging with fusion transrectal ultrasound guided prostate biopsy alone without a standard template biopsy is sufficient to evaluate patients with suspected prostate cancer. Our objective was to describe our experience with fusion targeted prostate biopsy and assess whether it could obviate the need for concomitant standard 12-core template prostate biopsy. MATERIALS AND METHODS: We retrospectively reviewed our prospectively collected database of patients who underwent fusion transrectal ultrasound guided prostate biopsy. All images and lesions were graded according to the Prostate Imaging Reporting and Data System, version 2. All patients underwent targeted biopsy followed by standard 12-core double sextant biopsy within the same session. Clinically significant prostate cancer was defined as Grade Group 2 or greater prostate cancer. RESULTS: A total of 506 patients were included in analysis. Indications were elevated prostate specific antigen with a previous negative prostate biopsy in 46% of cases, prostate cancer on active surveillance in 35%, elevated prostate specific antigen without a prior prostate biopsy in 15% and an isolated abnormal digital rectal examination in 3%. For standard vs fusion prostate biopsy the overall cancer detection rate was 57.7% vs 54.0% (p=0.12) and the clinically significant prostate cancer detection rate was 24.7% vs 30.8% (p=0.001). Of the 185 patients diagnosed with clinically significant prostate cancer 29 (16%) would have been missed if only targeted fusion prostate biopsy had been performed. CONCLUSIONS: Fusion targeted prostate biopsy is associated with a higher detection rate of clinically significant prostate cancer compared to standard double sextant biopsy. However, standard double sextant biopsy should still be performed as part of the routine fusion targeted prostate biopsy procedure to avoid missing a significant proportion of clinically significant prostate cancer.


Subject(s)
Biopsy, Large-Core Needle/methods , Image-Guided Biopsy/methods , Magnetic Resonance Imaging, Interventional/methods , Neoplasm Grading/methods , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnosis , Ultrasonography, Interventional/methods , Aged , Humans , Male , Reproducibility of Results , Retrospective Studies
20.
J Urol ; 201(4): 721-727, 2019 04.
Article in English | MEDLINE | ID: mdl-30664083

ABSTRACT

PURPOSE: At most centers strict age criteria are lacking for eligibility for active surveillance of prostate cancer. Younger men are often counseled to undergo definitive treatment despite limited data on the outcomes of active surveillance in younger men. We compared clinical characteristics and outcomes in men who enrolled in active surveillance at age less than 60 vs 60 years old or older. MATERIALS AND METHODS: We retrospectively reviewed the records of 2 institutional cohorts of a total of 2,084 men in whom prostate cancer was managed by active surveillance between 1995 and 2016. We compared outcomes in men who began active surveillance at age 60 vs 60 years or older using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 417 and 1,667 men who began active surveillance at younger than 60 and 60 years old or older, respectively, who met study inclusion criteria. At a median followup of 6.2 years we found no significant difference between men younger than 60 and 60 years old or older in the 5-year rates of biopsy progression-free survival (83% vs 83%), treatment-free survival (74% vs 71%), metastasis-free survival (99.7% vs 99.0%) or prostate cancer specific survival (100% vs 99.7%). Of the younger men 131 (31%) ultimately underwent treatment, including for pathological progression in 67% and prostate specific antigen progression in 18%. On multivariate analysis significant predictors of biopsy progression and progression to treatment among younger men were 20% or greater involvement of any core on diagnostic biopsy (HR 2.21, p = 0.003) and prostate specific antigen density 0.15 ng/ml/ml or greater (HR 1.93, p = 0.01). CONCLUSIONS: Active surveillance is a viable option in select men younger than 60 years with low volume, low risk prostate cancer. However, patients must be surveyed closely and understand the significant likelihood of ultimately requiring treatment.


Subject(s)
Prostatic Neoplasms/therapy , Watchful Waiting , Age Factors , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies
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