Abstract Background Preoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node ...dissection (ePLND). Objective To update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports. Design, setting, and participants Overall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified. Outcome measurements and statistical analysis A multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs). Results and limitations The median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA. Conclusions An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. Patient summary We developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI > 7% according to this model would significantly reduce the number of unnecessary pelvic nodal dissections with a risk of missing only 1.5% of patients with LNI.
Abstract Background No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our ...investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone. Materials and methods Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM). Results Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P <0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM ( P <0.001). Conclusions Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR.
PURPOSE OF REVIEWTo evaluate the role of prostatic inflammation in the development and progression of benign and malignant prostatic diseases.
RECENT FINDINGSPreclinical studies demonstrate that the ...activation of a chronic inflammatory prostatic response plays an important role in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Approximately 40–70% of patients with BPH-related lower urinary tract symptoms harbour chronic inflammation at pathologic evaluation. These individuals should be considered at increased risk of symptom progression and acute urinary retention. Although currently available drugs approved for the treatment of BPH do not have an anti-inflammatory activity, the development of novel molecules that target the inflammatory pathway represents a promising area in the pharmacological treatment of BPH. Preclinical evidences support a potential role of chronic prostatic inflammation in the malignant transformation of prostatic cells. However, clinical investigations on the association between prostatic inflammation and the risk of PCa report conflicting results.
SUMMARYMen with BPH-related lower urinary tract symptoms and chronic prostatic inflammation should be considered at increased risk of symptom progression and acute urinary retention during follow-up. Although preclinical studies provide a biological rationale for the relationship between inflammation and the risk of PCa, clinical investigations report conflicting results and the direct relationship between inflammation and malignant transformation in the human prostate is still debated.
Quality of life (QoL) outcomes in patients undergoing radical cystectomy (RC) with orthotopic neobladder (ONB) or ileal conduit (IC) have been extensively investigated. However, a general lack of ...consensus on QoL's predictive factors exists. The aim of the study was to develop a nomogram using preoperative parameters to predict global QoL outcome in patients with localized muscle-invasive bladder cancer (MIBC) undergoing RC with ONB or IC urinary diversion (UD).
A cohort of 319 patients who underwent RC and ONB or IC were retrospectively enrolled. Multivariable linear regression analyses were used to predict the global QoL score of the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), according to the patient characteristics and UD. A nomogram was developed and internally validated.
Patients' data in the two study groups significantly differed with regard to comorbidity profiles (chronic cardiac failure, p < 0.001; chronic kidney disease, p < 0.01; hypertension, p < 0.03; diabetic disease, p = 0.02; chronic arthritis, p = 0.02). A multivariable model that included patient age at surgery, UD, chronic cardiac disease, and peripheral vascular disease represented the basis for the nomogram. The calibration plot of the prediction model showed a systematic overestimation of the predicted global QoL score over the observed scores, with a slight underestimation for observed global QoL scores between 57 and 72. After performing leave-one-out cross-validation, the root mean square error (RMSE) emerged as 24.0.
A novel nomogram based completely on known preoperative factors was developed for patients with MIBC undergoing RC to predict a mid-term QoL outcome.
Objectives
Over the past decade, several systemic agents as docetaxel, cabazitaxel, sipuleucel-T, abiraterone and enzalutamide have improved overall survival (OS) in metastatic prostate cancer (mPCa) ...patients. However, to date the OS benefit was not demonstrated in population-based analysis.
Methods
Between 2004 and 2014, 19,047 men with de novo mPCa were identified within the Surveillance Epidemiology and End Results database. Median year of diagnosis resulted in two groups: historical (2004–2008) and contemporary (2009–2014). Due to potentially important differences according to year of diagnosis, we relied on propensity score matching. Propensity-score-matched Kaplan–Meier analyses and Cox regression models (CRMs) tested cancer-specific mortality (CSM) free survival and overall mortality (OM) free survival according to treatment period.
Results
The propensity-score-matched cohort consisted of 8596 patients with mPCa. Of those, 4298 (50.0%) were historical (2004–2008) and 4298 (50.0%) were contemporary (2009–2014). CSM free survival rates and OM free survival rate were 32 versus 36 months (
p
< 0.0001) and 26 versus 29 months (
p
< 0.0001) for, respectively, historical and contemporary patients. In multivariable CRMs, patients diagnosed in contemporary years had lower CSM (HR 0.88; CI 0.82–0.93) and OM (HR 0.88; CI 0.84–0.93) risks compared to historical counterpart (all
p
< 0.0001).
Conclusion
This population-based study provides the first evidence of improved CSM free survival and OM free survival in patients with de novo mPCa since the introduction of several systemic agents for CRPC patients.
Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ...clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (
, admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.
Abstract Background According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed ...at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa. Patients and methods Overall, 1,089 patients treated with radical prostatectomy with grade group 4 PCa at final pathology were identified. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen values≥0.2 ng/ml and rising. Clinical recurrence (CR) was defined as positive imaging after BCR. Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the impact of Gleason patterns on the risk of BCR and CR. Results Overall, 295 (27.1%), 651 (59.8%), and 143 (13.1%) patients had pathologic Gleason pattern 3+5, 4+4, and 5+3. Overall, 435 (39.9%) patients had positive margins and 439 (30.2%), 300 (27.5%), 350 (32.1%), and 216 (19.8%) had pT2, pT3a, pT3b/4, and pN1 disease. Median follow-up was 83 months. Overall, 536 and 221 patients experienced BCR and CR. The 10-year BCR- and CR-free survival rates were 42.9% and 67.5% vs. 38.3% and 59.7% vs. 40.6% and 50.4% for patients with pathologic Gleason pattern 3+5 vs. 4+4 vs. 5+3, respectively (all P ≤0.005). In multivariable analyses, patients with Gleason pattern 3+5 were at lower risk of BCR compared to those with 4+4 ( P = 0.002). Men with Gleason pattern 3+5 were at lower risk of CR compared to those with 4+4 and 5+3 (all P ≤ 0.01). Conclusions Patients with a primary Gleason score 3 are at reduced risk of recurrence as compared to their counterparts with 4 or 5. Primary and secondary Gleason scores should be considered to stratify the risk of recurrence after surgery in patients with grade group 4 PCa.
Objectives
To examine contemporary rates of pathological features and mortality for adenocarcinoma of the urinary bladder in the USA using population‐based data analysis.
Methods
We relied on 10 024 ...patients with non‐metastatic bladder cancer diagnosed between 2004 and 2013 within the Surveillance, Epidemiology and End Results registries. Logistic regression analyses focused on grade and stage. Kaplan–Meier analyses assessed cancer‐specific mortality rates in adenocarcinoma and urothelial carcinoma of the bladder. Cox regression analyses assessed the impact of histological subtype on cancer‐specific mortality.
Results
Overall, 215 (2.1%) adenocarcinoma and 9809 (97.9%) urothelial carcinoma patients were identified. The rate of non‐organ‐confined disease was higher in adenocarcinoma (64.7% vs 50.8%, P < 0.001). In multivariable logistic regression analyses, adenocarcinoma patients had a 2.2‐fold higher risk of harboring non‐organ‐confined disease (95% confidence interval 1.7–3.0; P < 0.001) than urothelial carcinoma patients. Cancer‐specific mortality‐free survival rates were lower in adenocarcinoma (P < 0.01). This disadvantage only applied to non‐organ‐confined disease (P = 0.044), and not to organ‐confined disease (P = 0.9). In multivariable Cox regression analyses, adenocarcinoma conferred a 1.3‐fold higher rate of cancer‐specific mortality (hazard ratio 1.30, 95% confidence interval 1.05–1.60; P = 0.01). Among adenocarcinoma patients, 30.7% harbored signet‐ring cell adenocarcinoma and portended particularly poor cancer‐specific mortality rates.
Conclusions
In bladder cancer, adenocarcinoma presents at higher stages than urothelial carcinoma. However, cancer‐specific mortality rates do not differ. A more unfavorable stage at diagnosis and higher cancer‐specific mortality apply to the signet‐ring cell variant.
Abstract Introduction To evaluate incidence of histological variants and grade agreement between transurethral resection (TUR) and radical cystectomy (RC) in patients with bladder cancer. Methods A ...total of 779 patients treated with TUR and subsequently with RC between 1990 and 2013 at a single center were analyzed retrospectively. Variant histology classifications used in our analyses were sarcomatoid, small cell, squamous, or micropapillary. Grade agreement was calculated using the Cohen kappa coefficient. Logistic regression analyses were built to predict adverse pathologic features from histological variants at TUR. Results Considering TUR, 213 (27.3%) patients were diagnosed with histological variants. Of these, 2.1% ( n = 16) were found with sarcomatoid variant, 1.7% ( n = 13) with small cell, 7.1% ( n = 55) with squamous, 12.5% ( n = 97) with micropapillary. Considering RC, 212 (27.2%) patients were diagnosed with histological variants. Poor agreement was found considering micropapillary variant and the presence of a histological variant in general (0.11 and 0.27, respectively). Intermediate agreement was found analyzing the presence of sarcomatoid, small cell, and squamous variants (0.43, 0.61, and 0.61, respectively). Small cell carcinoma at TUR was found associated with an increased risk of harboring positive soft tissue surgical margin (odds ratio = 2.08; CI: 1.27–3.41; P = 0.03). Conclusions One out of our patients with bladder cancer was diagnosed with a histological variant either at TUR and RC. We found poor agreement between TUR and RC. Our findings highlight that TUR alone is not sufficient to accurately evaluate the presence of histological variants that may have an effect on treatment and survival outcomes.
Long-term survival can be achieved in patients affected by localized prostate cancer (PCa) treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). However, development of ...a second primary tumor is still poorly investigated.
To investigate the impact of RP and EBRT on subsequent risk of developing bladder (BCa) and/or rectal cancer (RCa) among PCa survivors.
A total of 84397 patients diagnosed with localized PCa, treated with RP or EBRT between 1988 and 2009, and older than 65 yr of age were identified in the Surveillance, Epidemiology, and End Results Medicare insurance program-linked database. Our primary objective was to investigate the effect of EBRT and RP on the second primary BCa and RCa incidence.
Multivariable competing-risk regression analyses were performed to assess the risk of developing a second primary BCa or RCa.
Of the 84397 individuals included in the study, 33252 (39%) were treated with RP and 51145 (61%) with EBRT. Median follow-up was 69 months, and follow-up periods for patients who did not develop BCa, RCa, or pelvic cancer were 68, 69, and 68 mo, respectively. A total of 1660 individuals developed pelvic tumors (1236 BCa and 432 RCa). The 5- and 10-yr cumulative BCa incidence rates were 0.75% (95% confidence interval CI: 0.64–0.85%) and 1.63% (95% CI: 1.45–1.80%) versus 1.26% (95% CI: 1.15–1.37%) and 2.34% (95% CI: 2.16–2.53%) for patients treated with RP versus EBRT, respectively. The 5- and 10-yr cumulative RCa incidence rates were 0.32% (95% CI: 0.25–0.39%) and 0.73% (95% CI: 0.61–0.85%) versus 0.36% (95% CI: 0.30–0.41%) and 0.69% (95% CI: 0.60–0.79%) for patients treated with RP versus EBRT, respectively. On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18–1.55; p<0.001), but not RCa (p=0.4). Limitations include lack of information regarding the dose of radiotherapy and the retrospective nature with the implicit risk of selection bias.
Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. These results need to be validated in a well-designed randomized prospective trial.
We retrospectively analyzed the risk of developing a second primary bladder or rectal cancer during follow-up for patients treated with radical prostatectomy or external beam radiotherapy for a localized prostate cancer. We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor.
Patients treated with external beam radiotherapy for a localized prostate cancer are at an increased risk of developing a second bladder cancer tumor compared with those treated with radical prostatectomy. Conversely, no differences regarding rectal cancer incidence were reported between the two techniques.
