Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

Advanced patient age is associated with inferior cancer-specific survival after radical nephroureterectomy

Study Type – Prognosis (case series) Level of Evidence 4To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy ( P  ≤ 0.026). In multivariable analyses, being older was associated with decreased all-cause (AC) survival (>60 years) and cancer-specific survival (CSS; >80 years) after controlling for the effects of standard pathological features ( P  ≤ 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS.Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host’s defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78588/1/j.1464-410X.2009.09072.x.pd

No evidence for seasonal variations of the incidence of testicular germ cell tumours in Germany.

The pathogenesis of testicular germ cell tumours (GCTs) is still incompletely understood. Any progress in its understanding must derive from observational studies. Recently, it has been suggested that the incidence of GCTs may follow a seasonal pattern based on circannual changes in the Vitamin D serum levels, with maximum incidence rates in winter months. To examine this promising hypothesis, we studied monthly incidence rates of testicular GCTs in Germany by analysing 30,988 GCT cases aged 15-69 years, diagnosed during 2009-2019. Monthly incident case numbers with data regarding histology and patient age were obtained from the Robert Koch Institut, Berlin, along with annual male population counts. We used precision weighting for deriving pooled monthly incidence rates for GCTs of the period 2009-2019. We stratified pooled rates by histology (seminoma and nonseminoma) and age (15-39 and 40-69 years). By assuming a cyclical effect, we used an estimator of the intensity of seasonal occurrence and report seasonal relative risks (RR). The mean monthly incidence rate was 11.93/105 person-months. The seasonal RR for testicular cancer over-all is 1.022 (95% CI 1.000-1.054). The highest seasonal RR was found in the subgroup of nonseminoma aged 15-39 years, with a RR 1.044 (95% CI 1.000-1.112). The comparison of the pooled monthly rates of the winter months (October-March) with the summer months (April-September) revealed a maximum relative difference of 5% (95% CI 1-10%) for nonseminoma, aged 15-39 years. We conclude that there is no evidence of a seasonal variation of incidence rates of testicular cancer. Our results are at odds with an Austrian study, but the present data appear sound because the results were obtained with precision weighted monthly incidence rates in a large population of GCT cases

Testosterone and Prostate Cancer: Revisiting Old Paradigms

Context: Androgens are vital for growth and maintenance of the prostate; however, the notion that pathologic prostate growth, benign or malignant, can be stimulated by androgens is a commonly held belief without scientific basis. Therefore, the current prostatic guidelines for testosterone therapy (TT) appear to be overly restrictive and should be reexamined. Objective: To review the literature addressing the possible relationship between testosterone and prostate cancer (PCa) and to summarize the main aspects of this issue. Evidence acquisition: A Medline search was conducted to identify original articles, review articles, and editorials addressing the relationship between testosterone and the risk of PCa development, as well as the impact of TT on PCa development and its natural history in men believed to be cured by surgery or radiation. Evidence synthesis: Serum androgen levels, within a broad range, are not associated with PCa risk. Conversely, at time of PCa diagnosis, low rather than high serum testosterone levels have been found to be associated with advanced or high-grade disease. The available evidence indicates that TT neither increases the risk of PCa diagnosis nor affects the natural history of PCa in men who have undergone definitive treatment without residual disease. These findings can be explained with the saturation model (which states that prostatic homeostasis is maintained by a relatively low level of androgenic stimulation) and with the observation that exogenous testosterone administration does not significantly increase intraprostatic androgen levels in hypogonadal men. It must, however, be recognized that the literature remains limited regarding the effect of TT on PCa risk. Nonetheless, the current European Association of Urology guidelines state that in hypogonadal men who were successfully treated for PCa, TT can be considered after a prudent interval. Conclusions: Although no controlled studies have yet been performed and there is a paucity of long-term data, the available literature strongly suggests that TT neither increases the risk of PCa diagnosis in normal men nor causes cancer recurrence in men who were successfully treated for PCa. Large prospective studies addressing the long-term effect of TT are needed to either refute or corroborate these hypotheses. © 2009 European Association of Urology.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Multicenter evaluation of guideline adherence for pelvic lymph node dissection in patients undergoing open retropubic vs. laparoscopic or robot assisted radical prostatectomy according to the recent German S3 guideline on prostate cancer

Pelvic lymph node dissection (PLND) is recommended for patients with prostate cancer (PCa) and significant risk for nodal metastases. This study aimed to assess guideline adherence regarding PLND according to the German S3 guideline as example for a national but highly used guideline on prostate cancer and to compare the rate of complications different approaches for radical prostatectomy (RP). Patients undergoing open (RRP), laparoscopic (LARP) or robot-assisted (RARP) RP in six centers in Germany and Austria were included. The primary endpoint was the total number of removed lymph nodes (LN) between the different surgical approaches according to recent guideline recommendations. Secondary endpoints were the number of patients undergoing a sufficient PLND, defined as a removal of at least 10 LN and associated complication rates. 2634 patients undergoing RP were included (RRP: 66%, RARP/LARP: 34%). PLND was performed in 88% (RRP: 88.5%, RARP/LARP: 86.8%, p = 0.208). In intermediateor high risk PCa, PLND was performed in 97.2% (RRP: 97.7%, RARP/LARP: 96.2, p = 0.048). Of those, the mean number of LN was 19 (RRP: 19 vs. RARP/LARP: 17, p < 0.005) and sufficient PLND was observed in 84.6% of RRP compared to 77.2% of RARP/LARP (p < 0.005). Symptomatic lymphoceles requiring surgical treatment occurred more often in RRP than in RARP/LARP (4.0% vs. 1.6%, p = 0.001). The general guideline adherence regarding performing PNLD and the LN yield is high, regardless of the surgical approach. As expected, lymph node yield was higher when very experienced surgeons conducted the procedure. This should be considered in patients' counseling

Revised manuscript R2, clean version are serum levels of 25-hydroxy vitamin D reduced following orchiectomy in testicular cancer patients?

Résumé Contexte Le testicule représente un lieu où le précurseur de la vitamine D est converti en sa forme active. Il a été suggéré que la perte d’un testicule pouvait induire une réduction des taux sériques de vitamine D. La carence en vitamine D représenterait un problème de santé important à long terme pour les patients présentant des tumeurs testiculaires à cellules germinales (TCG) puisque la plupart d’entre eux survivent. Le but de cette étude était de se tourner vers les taux sériques de 25(OH)-Vitamine D (25OHD) chez les patients présentant des TCG, avant et après orchidectomie. Au total, 177 patients avec TCG ont subi des mesures des taux sériques de 25OHD, dont 83 avec mesures préopératoires et 94 avec des mesures à six points de temps particuliers, de l’immédiat postopératoire jusqu’à plus de 24 mois. Des évaluations longitudinales des taux sériques de 25OHD ont été réalisées individuellement chez les patients avec des mesures répétées. Une seconde analyse a impliqué des cohortes de patients avec des mesures à six points de temps postopératoires. Les taux sériques des patients ont également été comparés à ceux de 2 groupes témoins, l’un composé de 84 patients atteints de maladies testiculaires non néoplasiques, et l’autre de 237 patients atteints de maladies urologiques non néoplasiques. Nous nous sommes également penchés sur les associations des taux de 25OHD avec les taux de testostérone, d’hormone folliculostimulante (FSH), l’âge, l’histologie de la TCG et la saison. Des méthodes statistiques descriptives ont été utilisées pour comparer les groupes et analyser les changements au fil du temps. Résultats Des taux sériques normaux de 25OHD ont été trouvés chez 21,7%, 23,1%, 20,2%, et 21,9% des patients avec GCT, respectivement en préopératoire et après >2 ans, ainsi que chez les patients du groupe témoin 1 et du groupe témoin 2. Les taux ont été significativement plus élevés au printemps et en été, mais aucune association n’a été observée avec d’autres paramètres. Nous avons retrouvé une diminution transitoire significative des taux de 25OHD avec un nadir à 6-12 mois après orchiectomie et un rétablissement par la suite. Conclusion Contrairement aux études précédentes, nous n’avons trouvé aucune réduction permanente des niveaux de sérum 25OHD après orchiectomie, mais une baisse postopératoire transitoire des taux de 25OHD. Il n’y avait pas d’associations entre les taux de 25OHD et l’âge, ni avec les taux de testostérone ou de FSH. Nos résultats peuvent mettre en avant un rôle particulier du testicule dans le métabolisme de la vitamine D et peuvent ainsi améliorer la compréhension des divers rôles physiologiques des testicules

Testicular Neoplasms: Primary Tumour Size Is Closely Interrelated with Histology, Clinical Staging, and Tumour Marker Expression Rates—A Comprehensive Statistical Analysis

The role of primary tumour size (TS) in the clinical course of testicular tumours is incompletely understood. We retrospectively evaluated 641 consecutive patients with testicular neoplasms with regard to TS, histology, clinical stage (CS), serum tumour marker (STM) expression and patient age using descriptive statistical methods. TS ≤ 10 mm was encountered in 13.6% of cases. Median TS of 10 mm, 30 mm, 35 mm, and 53 mm were found in benign tumours, seminomas, nonseminomas, and other malignant tumours, respectively. In cases with TS ≤ 10 mm, 50.6% had benign tumours. Upon receiver operating characteristics analysis, TS of > 16 mm revealed 81.5% sensitivity and 81.0% specificity for detecting malignancy. In subcentimeter germ cell tumours (GCTs), 97.7% of cases had CS1, and CS1 frequency dropped with increasing TS. Expression rates of all STMs significantly increased with TS. MicroRNA-371a-3p (M371) serum levels had higher expression rates than classical STMs, with a rate of 44.1% in subcentimeter GCTs. In all, TS is a biologically relevant factor owing to its significant associations with CS, STM expression rates and histology. Importantly, 50% of subcentimeter testicular neoplasms are of benign nature, and M371 outperforms the classical markers even in subcentimeter tumours

Thromboprophylaxis and the route of administration of chemotherapy in testicular cancer patients in German-speaking countries

Due to the excellent cure rates for testicular cancer (TC), focus has shifted towards decreasing therapy-related morbidities. Thrombosis is a frequent complication of cisplatin chemotherapy. Furthermore, the optimal route of administration for chemotherapy is still under debate. The purpose of this study was to assess the patterns of care concerning dosing and duration of thromboprophylaxis currently utilized in TC patients in German-speaking countries as well as the route of chemotherapy administration. A standardized questionnaire was sent to all members of the German TC Study Group (GTCSG) and to all the urological university hospitals in Germany. The questionnaire was also sent to the oncologic clinics at those universities where urologists do not administer chemotherapy. The response rate was 87% (55/63). Prophylactic anticoagulation with low-molecular-weight heparin (LMWH) was administered in 94% of the clinics. The dosing of LMWH was prophylactic (85%), high prophylactic (adjusted to bodyweight) (7%), or risk adapted (9%). After completion of chemotherapy, anticoagulation was continued in 15 clinics (33%) for 2 to 24 weeks, while the remainder stopped the LMWH upon cessation of chemotherapy. Chemotherapy was administered via central venous access in 59%, peripheral IV in 27%, or both in 14% of the clinics. Most of the institutions performed some form of thromboprophylaxis, although the modes of application varied by institution type and amongst the urologists and oncologists. Prospective studies are needed to evaluate the incidence, date of occurrence, and risk factors of venous thrombosis during TC chemotherapy to provide a recommendation concerning prophylactic anticoagulation

Androgen deprivation therapy for the treatment of prostate cancer: consider both benefits and risks

CONTEXT: Androgen deprivation therapy (ADT) is increasingly used for the treatment of prostate cancer (PCa), even in clinical settings in which there is no evidence-based proof of prolonged overall survival (OS). ADT, however, may be associated with numerous side effects, including an increased therapy-related cardiovascular mortality. OBJECTIVE: To discuss different clinical settings in which ADT is currently used and to critically weigh the benefits of ADT against its possible side effects. EVIDENCE ACQUISITION: A MEDLINE search was conducted to identify original articles and review articles addressing the efficacy and side effects of ADT for the treatment of PCa. Keywords consisted of prostate cancer, hormonal therapy, adverse effects, radical prostatectomy, and radiotherapy. The articles with the highest level of evidence for the various examined end points were identified with the consensus of all authors and were reviewed. EVIDENCE SYNTHESIS: Even short-term use of ADT may lead to numerous side effects, such as osteoporosis, obesity, sarcopenia, lipid alterations, insulin resistance, and increased risk for diabetes and cardiovascular morbidity. Despite these side effects, ADT is commonly used in various clinical settings in which a clear effect on improved OS has not been shown. CONCLUSIONS: ADT is associated with an increased risk of multiple side effects that may reduce quality of life and/or OS. Consequently, these issues should be discussed in detail with patients and their families before initiation of ADT. ADT should be used with knowledge of its potential long-term side effects and with possible lifestyle interventions, especially in settings with the highest risk-benefit ratio, to alleviate comorbidities