Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of ...function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.
Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive ...treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.
The evolution in the past decade of recommendations for prostate cancer (PCa) management, from screening to surgical treatment, may have affected the radical prostatectomy (RP) landscape. However, ...comprehensive data at a national level remain scarce. We extracted 5-yr data for RP patients in France from the central database of the national health care system. The primary endpoints were surgical approach (open ORP, laparoscopic LRP, and robot-assisted RP RARP), length of stay (LOS), and complication and readmission rates. The annual number of RPs was stable during the study period. The proportion of RARPs increased from 39.8% in 2015 to 52.6% in 2019, whereas the proportion of ORPs decreased from 34.4% to 24.5%. LOS continuously decreased over time irrespective of the surgical approach. The proportion of centres in the highest quartile of hospital volume increased from 22.0% to 28.3% (p = 0.006). LOS and complication and readmission rates were significantly lower (p < 0.001) in the LRP cohort at each time point. National trends confirmed that RARP progressively replaced ORP, with a stable number of annual RPs over time. Greater centralisation and better early postoperative outcomes were observed with laparoscopy.
We reviewed French data for patients undergoing removal of the prostate for prostate cancer between 2015 and 2019. We found that robot-assisted minimally invasive surgery has increased over time and the length of hospital stays has decreased. Rates of complications and readmission were lower with minimally invasive surgery.
There are no countrywide data regarding the utilization of same-day-discharge (SDD) surgery for robot-assisted radical prostatectomy (RARP). We aimed to evaluate the annual number of SDD RARP ...procedures in France and to compare postoperative outcomes in SDD versus non-SDD centers. Data for all 9651 patients undergoing RARP in France in 2020 were extracted from the central database of the national healthcare system. Endpoints were length of hospital stay, patient age, center volume, lymph node dissection, and the hospital readmission rate. Overall, 184 SDD cases (1.9%) were reported in 14.2% of RARP centers. The annual RARP and SDD RARP caseload ranged from 41 to 485, and from one to 47, respectively, in SDD centers. SDD was significantly associated with higher-volume centers (p < 0.001). No difference in readmission rate (7.9% vs 5.1%; p = 0.141) was observed for SDD versus non-SDD centers. Direct stay costs were estimated at €1457 in SDD centers compared to €2021 in non-SDD centers. The main limitation is the lack of detailed patient characteristics and readmission causes. This annual nationwide analysis suggests that SDD RARP remains infrequently used in routine practice in France despite being associated with comparable short-term outcomes after RARP and potential cost benefits.
We evaluated the use of robot-assisted removal of the prostate (RARP) with same-day hospital discharge in France for men with prostate cancer. In 2020, only 1.9% of the 9651 RARP procedures involved same-day discharge, even though the data show that this approach has lower costs and comparable safety.
We found a significant association between vasectomy and any-grade, localized, and advanced prostate cancer. However, the effect estimates were increasingly close to null when examining studies of ...robust design and high quality. Future well-designed studies with attention to potential residual confounders, which were not taken into account in large cohort studies, are needed.
Previous reports have shown an association between vasectomy and prostate cancer (PCa). However, there exist significant discrepancies between studies and systematic reviews due to a lack of strong causal association and residual confounding factors such as prostate-specific antigen (PSA) screening.
To assess the association between vasectomy and PCa, in both unadjusted and PSA screen-adjusted studies.
We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The PubMed, Scopus, and Web of Science databases were searched in January 2022 for studies that analyzed the association between vasectomy and PCa.
A total of 37 studies including 16 931 805 patients met our inclusion criteria. A pooled analysis from all studies showed a significant association between vasectomy and any-grade PCa (odds ratio OR 1.23; 95% confidence interval CI, 1.10–1.37; p < 0.001; I2 = 96%), localized PCa (OR 1.08; 95% CI, 1.06–1.11; p < 0.00001; I2 = 31%), or advanced PCa (OR 1.07; 95% CI, 1.02–1.13; p = 0.006; I2 = 0%). The association with PCa remained significant when the analyses were restricted to studies with a low risk of bias (OR 1.06; 95% CI, 1.02–1.10; p = 0.02; I2 = 48%) or cohort studies (OR 1.09; 95% CI, 1.04–1.13; p < 0.0001; I2 = 64%). Among studies adjusted for PSA screening, the association with localized PCa (OR 1.06; 95% CI, 1.03–1.09; p < 0.001; I2 = 0%) remained significant. Conversely, vasectomy was no longer associated with localized high-grade (p = 0.19), advanced (p = 0.22), and lethal (p = 0.42) PCa.
Our meta-analysis found an association between vasectomy and any, mainly localized, PCa. However, the effect estimates of the association were increasingly close to null when examining studies of robust design and high quality. On exploratory analyses including studies, which adjusted for PSA screening, the association for aggressive and/or advanced PCa diminished.
In this study, we found an association between vasectomy and the risk of developing localized prostate cancer without being able to determine whether the procedure leads to a higher prostate cancer incidence.
Despite recent improvements in survival, metastatic castration-resistant prostate cancers (mCRPCs) remain lethal. Alterations in genes involved in the homologous recombination repair (HRR) pathway ...are associated with poor prognosis. Poly-ADP-ribose polymerase (PARP) inhibitors (PARPis) have demonstrated anti-tumoral effects by synthetic lethality in patients with mCRPCs harboring HRR gene alterations, in particular
. While both olaparib and rucaparib have obtained government approvals for use, the selection of eligible patients as well as the prescription of these treatments within the clinical urology community are challenging. This review proposes a brief review of the rationale and outcomes of PARPi treatment, then a pragmatic vision of PARPi use in terms of prescription and the selection of patients based on molecular screening, which can involve potential genetic counseling in the case of associated germinal alterations.
Abstract Purpose Median age for the diagnosis of metastatic bladder cancer (MBC) is 73 years. The feasibility of chemotherapy in older patients is controversial. Our objectives were to assess ...associations linking age to first line chemotherapy regimen selection, early chemotherapy discontinuation, and 1-year mortality in everyday practice. Materials and methods Between 1999 and 2011, 197 consecutive patients aged≥70 years with MBC referred to 4 hospitals were included in the AGEVIM multicenter cohort. At baseline, we recorded performance status (PS); tumor characteristics; the Charlson Comorbidity Index; and plasma creatinine, hemoglobin, and albumin. Early discontinuation data were available for 193 patients, and overall 1-year mortality for 180 patients. We assessed the probabilities of initial cisplatin-based combination chemotherapy (CCC), early discontinuation (≤2 cycles), and 1-year mortality, using multivariate logistic regression and Cox proportional hazards modeling. Results Among the 193 patients (mean age: 76±4.3 y), with 2 metastatic site in median 43.5% received CCC, 36.3% gemcitabine and carboplatin, and 20.2% gemcitabine alone. The probability of CCC decreased with age independently from sex, PS, creatinine clearance, and Charlson Comorbidity Index ( P <0.0001), early discontinuation occurred in 24.9% of patients. Factors independently associated with global chemotherapy early discontinuation were age (adjusted odds ratioper additional year = 1.11; 95% CI: 1.02–1.20; P = 0.01) and higher metastatic-site number (adjusted odds ratioper additional site = 1.45; 95% CI: 1.08–1.95; P = 0.01). The number of patients was too small for a robust analysis of factors associated with early chemotherapy discontinuation in each chemotherapy regiment subgroup. Independent predictors of 1-year mortality (median = 9.6 mo) were early discontinuation (adjusted hazard ratio aHR = 4.77 2.85–7.96 when PS<2 and 20.6 9.43–44.82 when PS≥2; P <0.0001), albumin<35 g/l (aHR = 3.06 1.81–5.17, P = 0.0001), creatinine clearance<30 ml/min (aHR = 2.96 1.45–6.06, P = 0.009), and higher metastatic-site number (aHR = 1.34 1.14–1.56, P <0.0001). Conclusion Less than half of older patients with MBC received initial CCC and 25% had≤2 cycles of chemotherapy. Older age was associated with decreased CCC prescription, independently from known contraindications, and with global chemotherapy early discontinuation, but not with 1-year mortality.
Background: Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for imaging and/or ...treatment. We reviewed potential targets other than PSMA for PCa theranostics in nuclear medicine that have already been tested in humans. Methods: We performed a systematic web search in the PubMed and Cochrane databases, with no time restrictions by pooling terms (“prostate cancer”, “prostatic neoplasms”) and (“radioligand”, “radiotracer”). Included articles were clinical studies. The results were synthetized by the target type. Results: We included 38 studies on six different targets: gastrin-releasing peptide receptors (GRPRs) (n = 23), androgen receptor (n = 11), somatostatin receptors (n = 6), urokinase plasminogen activator surface receptor (n = 4), fibroblast activation protein (n = 2 studies) and integrin receptors (n = 1). GRPRs, the most studied target, has a lower expression in high-grade PCa, CRPC and bone metastases. Its use might be of higher interest in treating earlier stages of PCa or low-grade PCa. Radiolabeled fibroblast activation protein inhibitors were the most recent and promising molecules, but specific studies reporting their interest in PCa are needed. Conclusion: Theranostics in nuclear medicine will continue to develop in the future, especially for PCa patients. Targets other than PSMA exist and deserve to be promoted.
Abstract Background The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ...ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer–specific morbidity and mortality, time to castration resistance, and overall survival (OS). Methods We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. Results The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. Conclusion The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients.
Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer ...(PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin‐like polychlorinated biphenyl congener 153 (PCB‐153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow‐up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39–4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB‐135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.
What's new?
Some environmental chemicals can mimic human hormones, and may spur cancer progression. Here, the authors studied the effect of three prevalent organic chemicals on prostate cancer recurrence: the estrogenic insecticide chlordecone; DDE, a stable metabolite of DDT which has anti‐androgenic properties; and PCB‐153, which has estrogenic and anti‐estrogenic properties. No effect was associated with DDE or PCB‐153. However, those in the highest exposure quartile for chlordecone had 2‐fold increased risk of biochemical recurrence, defined as two consecutive elevated PSA measurements, after prostatectomy. These findings add to the evidence that environmental estrogens could promote cancer progression.
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