BACKGROUND
Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [−2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA × √tPSA, was evaluated in a multicenter study for detecting PCa.
METHODS
A total of 1362 patients from 4 different study sites who had tPSA values of 1.6–8.0 μg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter).
RESULTS
The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score.
CONCLUSIONS
The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6–8.0 μg/L (i.e., approximately 2–10 μg/L in traditional calibration) and is better able to detect aggressive PCa.
Ureteral and multifocal tumours had a worse prognosis than renal pelvic tumours. These findings are not in line with recently published data and should be investigated in a prospective assessment to obtain a definitive statement regarding this matter.
In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract.
Study Type – Diagnostic (exploratory cohort)
Level of Evidence 3a
What's known on the subject? and What does the study add?
Hereditary non‐polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant multi‐organ cancer syndrome. Upper urinary tract urothelial carcinomas belong to HNPCC‐related tumours and rank third within this group after colorectal and endometrial cancer. However, many urologists are not aware of this association and it is presumed that some hereditary cancers are misclassified as sporadic and that their incidence is underestimated. Consequently, family members of patients with upper urinary tract urothelial carcinomas secondary to HNPCC may be denied appropriate surveillance and early detection.
A significant proportion of patients (21.3%) with newly diagnosed upper urinary tract urothelial carcinomas may have underlying HNPCC. Demographic and epidemiological characteristics suggest different mechanisms of carcinogenesis among this population. Recognition of such potential is essential for appropriate clinical and genetic management of patients and family. In order to help to identify these patients, we propose a patient‐specific checklist.
OBJECTIVE
To identify, based on previously described clinical criteria, hereditary upper urinary tract urothelial carcinomas (UUT‐UCs) that are likely to be misclassified as sporadic although they may belong to the spectrum of hereditary non‐polyposis colorectal cancer (HNPCC) associated cancers.
PATIENTS AND METHODS
We identified, using established clinical criteria, suspected hereditary UUT‐UC among 1122 patients included in the French national database for UUT‐UC.
Patients were considered at risk for hereditary status in the following situations: age at diagnosis <60 years with no previous history of bladder cancer; previous history of HNPCC‐related cancer regardless of age; one first‐degree relative with HNPCC‐related cancer diagnosed before 50 years of age or two first‐degree relatives diagnosed regardless of age.
RESULTS
Overall, 239 patients (21.3%) were considered to be at risk of hereditary UUT‐UC.
Compared with sporadic cases, hereditary cases are more likely to be female (P= 0.047) with less exposure to tobacco (P= 0.012) and occupational carcinogens (P= 0.037). A greater proportion of tumours were located in the renal pelvis (54.5% vs 48.4%; P= 0.026) and were lower grade (40% vs 30.1%; P= 0.015) in the hereditary cohort.
The overall, cancer‐specific and recurrence‐free survival rates were similar in both cohorts.
We propose a patient‐specific risk identification tool.
CONCLUSIONS
A significant proportion (21.3%) of patients with newly diagnosed UUT‐UC may have underlying HNPCC as a cause.
Recognition of such potential and application of a patient‐specific checklist upon diagnosis will allow identification and appropriate clinical and genetic management for patient and family.
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