•Time to mCRPC and OS differences can be observed for De Novo vs. secondary mHSPC patients.•After stratification according to metastatic disease volume, patients with DNHV mHSPC harbored the worst ...outcomes, while patients with SecLV mHSPC harbored best prognosis.•These effects can also be observed after progression to mCRPC.
In recently published phase III trials, overall survival (OS) differences were demonstrated in patients with secondary vs. De Novo and low vs. high volume metastatic hormone-sensitive prostate cancer (mHSPC). We hypothesized that these factors may also be attributable in real-world setting of new intensified combination therapies and in metastatic castration resistant prostate cancer (mCRPC) patients.
We relied on an institutional tertiary-care database to identify mHSPC and subsequent mCRPC patients. The main outcome consisted of time to mCRPC and OS. Patients were stratified according to De Novo vs. secondary and low vs. high volume mHSPC and mCRPC, respectively.
Of 504 mHSPC patients, 371 (73.6%) were De Novo vs. 133 (26.4%) secondary mHSPC. Patients with De Novo and high volume mHSPC harbored shorter time to mCRPC and OS than secondary and low volume mHSPC patients (both P < 0.01). After stratification regarding disease volume, median time to mCRPC differed significantly between De Novo high volume (DNHV) vs. De Novo low volume (DNLV) vs. secondary high volume (SecHV) vs. secondary low volume mHSPC patients (SecLV, P < 0.001). Similarly in OS analyses, median OS was 44 vs. 53 vs. 88 vs. 120 months for respectively DNHV vs. SecHV vs. SecLV vs. DNLV mHSPC (P < 0.001). After progression to mCRPC, the effect of onset of metastatic disease and metastatic volume was still observed (all P < 0.01).
Patients with DNHV mHSPC harbor worse prognosis in a real world setting and in the light of combination therapies. This effect is also discernible in the context of mCRPC.
Objective
To prospectively evaluate the role of fluorescence-guided cystoscopy in a high-risk bladder cancer population undergoing screening based on a multi-marker panel of urine-tests (
...UroScreen-study
).
Patients and methods
UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of workers with occupational exposure to aromatic amines. Voluntary annual screens were done in 1,609 men. Cytology, quantitative NMP22® assay, and UroVysion (FISH) were applied to 7091 urine samples. Subjects with at least one positive urine-based tumor marker and/or persisting microscopic hematuria were offered fluorescence-guided (PDD) instead of white light cystoscopy. In case of suspicious findings histopathological evaluation by transurethral biopsy was performed. Data were statistically summarized and compared to tumors found by the standard algorithm of the screening study.
Results
Twenty-two subjects with a mean age of 58 years (39–72) underwent PDD cystoscopy. Of those 3 had positive NMP22 tests, 14 positive FISH tests and 9 suspicious cytologies. Two had persisting microscopic hematuria only. PDD cystoscopy revealed enhanced unifocal fluorescence in 14. All had subsequent transurethral biopsy or resection. In total, 1 urothelial carcinoma (pTaG1, low grade) was diagnosed. In the other participants urothelial cancer of the bladder was ruled out. Chronic cystitis was revealed in 8 of 14 biopsies. No higher detection rate was found using PDD than with the standard algorithm of the
UroScreen
study in which 17 tumors were detected by white light cystoscopy.
Conclusion
The use of PDD does not lead to a higher cancer detection rate in a high-risk screening population. Larger sample sizes may be needed to ultimately asses the value of PDD for bladder cancer screening.
Abstract only
e15195
Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo ...plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.
Metachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by ...primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset.
We relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa.
Of 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS.
Timing of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa.
Onset of metastatic disease for prostate. Cancer (PCa) might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset. We relied on an institutional tertiary-care database and found that timing of smPCa is strongly influenced by GS and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of smPCa.
Non-metastatic castration-resistant prostate carcinoma (M0CRPC) is associated with an increased risk of progression and mortality, especially if the prostate-specific antigen doubling time is short ...(PSADT ≤ 10 months). The risk of progression and mortality increases even further if the disease progresses to the metastatic stage (mCRPC). The androgen receptor inhibitors apalutamide, darolutamide and enzalutamide, each in combination with androgen deprivation therapy (ADT), are available for the treatment of patients with high-risk M0CRPC.Data from the pivotal SPARTAN study showed that apalutamide + ADT delayed metastasis-free survival (MFS) and thus also the development of mCRPC in these patients. Prior to the approval of apalutamide in the European Union, the active substance was available in Germany as part of an international compassionate use program. A total of 109 patients from 50 centres participated in Germany: 45 patients were treated for more than 3 months and 13 patients for more than 6 months. The compassionate use program continues in some countries; 556 patients have been enrolled worldwide.In our experience, this real-world population showed a good PSA response, which was also shown for this exploratory endpoint in the SPARTAN study. We were also unable to identify any significant differences from the pivotal trial with regards to the tolerability profile.Apalutamide in combination with ADT was also effective in this real-world population and led to a rapid decrease in PSA. The tolerability profile did not differ from that in the SPARTAN trial.
Zusammenfassung
Hintergrund
Die Behandlung mittels Androgendeprivationstherapie (ADT) plus erweiterter Hormontherapie (ARTA) stellt die Standardtherapie beim metastasierten hormonsensiblen ...Prostatakarzinom (mHSPC) dar. Neue Daten von Triplet-Kombinationstherapien aus ADT + ARTA (Abirateron/Darolutamid) + Docetaxel-Chemotherapie zeigten einen Überlebensvorteil für gewisse mHSPC-Patientengruppen.
Fragestellung
Welches Therapieansprechen ist im Real-world-mHSPC-Setting mittels Triplet-Kombinationstherapie zu erwarten und welche Nebenwirkungen treten gehäuft auf?
Ergebnisse
Alle Patienten, die eine Triplet-Kombinationstherapie aus ADT + ARTA (Abirateron/Darolutamid) + Docetaxel erhalten haben, wurden für die vorliegende Studie eingeschlossen. Insgesamt konnten 14 Patienten mit einem medianen Alter von 62 Jahren und 10/14 Abirateron- bzw. 4/14 Darolutamid-Therapien inkludiert werden. Der mediane PSA vor Therapiebeginn lag bei 77 (IQR 44–150) ng/ml. Insgesamt hatten 86 % der Patienten einen PSA-Abfall > 90 % unter Therapie und der mediane PSA-Nadir lag bei 0,3 ng/ml. Schwerwiegende Nebenwirkungen (Grad III) unter der Triplet-Therapie traten bei insgesamt 2 Patienten (14,2 %) auf mit fieberhafter Neutropenie 7,1 % (1/14) bzw. Gastroenteritis und Infektgeschehen 7,1 % (1/14). Leichtgradige Nebenwirkungen (Grad I/II) wie Polyneuropathie (1/14), Mukositis (1/14), Xerostomie (1/14), Gewichtsverlust (1/14) und Fatigue (3/14) wurden ebenso detektiert. Die Chemotherapie wurde bei einem Patienten aufgrund von Nebenwirkungen unterbrochen. Nach einem medianen Follow-up von 10 (IQR: 7–17) Monaten zeigten sich 2 Patienten (14,2 %) mit Progression zu einer Kastrationsresistenz.
Zusammenfassung
Die Triplet-Therapie zeigt sich im klinischen Alltag mit einem sehr guten PSA-Ansprechen. Nebenwirkungen unter der Therapie sind v. a. durch die klassische Chemotherapie getriggert.
What's known on the subject? and What does the study add?
UroVysion
™ is a multicolour fluorescence
in situ
hybridisation assay that detects
DNA
gain at chromosomes 3, 7 and 17 and loss at the 9p21 ...locus in exfoliated urothelial cells. This cell‐based test is time‐consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer.
We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between
DNA
gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay.
Objective
To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysion™ assay regarding screening.
Subjects and Methods
In all, 1609 men took part in the prospective study
UroScreen
. Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010.
In all, 191 434 cells in 6517
UroVysion
tests were analysed for copy number variations (
CNV
) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men.
We assessed
CNVs
at single or multiple loci using polysomy indices (
PIs
, called multiple
PI
and
PI
3,
PI
7 and
PI
17).
We calculated Spearman's rank correlation coefficients (r
s
) between these
PIs
and receiver operating characteristic (
ROC
) curves with areas under the curves (
AUCs
). We applied Cox regression to estimate hazard ratios (
HRs
) to assess the risk of developing bladder cancer.
Results
Nine out of 21 bladder tumours detected in 20 participants (‘cases’) had a positive UroVysion test, including seven high‐grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually.
No case was found because of a complete loss of 9p21 in at least 12 cells.
There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between r
s
= 0.98 and r
s
= 0.99 in cases and between r
s
= 0.84 and r
s
= 0.88 in non‐cases (
P
< 0.001). Associations were less pronounced with
CNVs
at 9p21 among cases and were lacking in non‐cases.
Estimates of the relative risk of
DNA
gain for developing a bladder tumour assessed with
PIs
(threshold 10% of cells) were 47.7 (95% confidence interval
CI
18.3–124.1) for the multiple
PI
, 44.5 (95%
CI
16.5–119.9) for
PI
3, 34.7 (95%
CI
13.1–92.1) for
PI
7 and 52.4 (95%
CI
20.7–132.6) for
PI
17, as well as 7.9 (95%
CI
3.0–20.6) for a complete loss of 9p21 (threshold 2.5% of cells), respectively.
ROC
analyses showed similar
AUCs
for multiple
PI
compared with
PIs
of single chromosomes 3, 7 and 17 (all
AUCs
between 0.79 and 0.80) and a lower
AUC
for a homozygous loss of 9p21 (
AUC
0.72).
Conclusions
The UroVysion assay showed a reasonable performance in detecting bladder cancer in the present study population and shared positive test results with cytology, which is much cheaper.
A simpler, faster and cheaper version of the UroVysion assay might rely on the very strong correlations between gains at chromosomes 3, 7 and 17, resulting in a similar performance in detecting bladder cancer with single‐probe
PIs
compared with the full set of these probes.
Loss of 9p21 was less predictive for developing bladder cancer in
UroScreen
.
We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment ...characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States.
Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group IGCCCG prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection RPLND status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used.
In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004).
We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.
Our study analyzed regional variations in patient demographics, tumor prognostics, and treatment outcomes among stage III nonseminoma germ cell tumor patients using the SEER database. It found significant differences in systemic therapy and retroperitoneal lymph dissection rates, as well as cancer-specific mortality across regions, suggesting potential disparities in care quality or expertise.
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