Beyond PSA: The Role of Prostate Health Index (phi) Ferro, Matteo; De Cobelli, Ottavio; Lucarelli, Giuseppe ...
International journal of molecular sciences,
02/2020, Letnik:
21, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly including indolent cancer. ...Availability of different therapeutic strategies which have a very different impact on the patient's quality of life suggested a strong need for tools able to identify clinically significant cancer at diagnosis. Multi-parametric magnetic resonance showed very good performance in pre-biopsy diagnosis. However, it is an expensive tool and requires an experienced radiologist. In this context, a simple blood-based test is worth investigating. In this context, researchers focused their attention on the development of a laboratory test able to minimize overdiagnosis without losing the identification of aggressive tumors.
Recent literature data on PCa biomarkers revealed a clear tendency towards the use of panels of biomarkers or a combination of biomarkers and clinical variables. Phi, the 4Kscore, and Stockholm3 as circulating biomarkers and the Mi-prostate score, Exo DX Prostate, and Select MD-X as urinary biomarker-based tests have been developed. In this scenario, phi is worthy of attention as a noninvasive test significantly associated with aggressive PCa.
Literature data showed that phi had good diagnostic performance to identify clinically significant (cs) PCa, suggesting that it could be a useful tool for personalized treatment decision-making. In this review, phi potentialities, limitations, and comparisons with other blood- and urinary-based tests were explored.
Background: Pelvic lymphnode dissection (PLND) is an integral part of surgical treatment for localized intermediate and high-risk prostate cancer. The most common complication of PLND is lymphocele ...formation. In the majority of cases the development of lymphoceles is clinically asymptomatic but in case of symptomatic/infected lymphocele an active treatment is required. The aim of this article is to analyse the current evidence on the treatment of symptomatic/infected lymphocele trough robotic approach. Materials and Methods: The search was applied to PubMed, EMBASE, and Cochrane databases with following terms: “lymphocele”, “symptomatic”, “infected”, “robot-assisted AND radical prostatectomy”, “robot-assisted”, “treatment”. Results: The search identified three series focusing on the treatment by robot-assisted approach of symptomatic and/or infected lymphocele. The main and most frequent reason for performing the robotic treatment was an infected lymphocele, the median time from robot-assisted radical prostatectomy and PLND to robotic treatment of lymphocele was 118 days (range 30-240). Robot-assisted treatment was successful in all reports. Conclusions: The drainage of lymphocele with the robot-assisted approach appeared safe, feasible, and with satisfactory outcomes for the definitive treatment of symptomatic/infected lymphocele.
We evaluated possible factors predicting testicular cancer in patients undergoing testis sparing surgery.
We retrospectively analyzed the records of all patients who underwent testis sparing surgery ...for a small testicular mass at a total of 5 centers. All patients with 1 solitary lesion 2 cm or less on preoperative ultrasound were enrolled in the study. Testis sparing surgery consisted of tumor enucleation for frozen section examination. Immediate radical orchiectomy was performed in all cases of malignancy at frozen section examination but otherwise the testes were spared. Univariate and multivariate analysis were performed and ROC curves were produced to evaluate preoperative factors predicting testicular cancer.
Overall 147 patients were included in the study. No patient had elevated serum tumor markers. Overall 21 of the 147 men (14%) presented with testicular cancer. On multivariate analysis the preoperative ultrasound diameter of the lesion was a predictor of malignancy (OR 6.62, 95% CI 2.26-19.39, p=0.01). On ROC analysis lesion diameter had an AUC of 0.75 (95% CI 0.63-0.86, p=0.01) to predict testicular cancer. At the best cutoff of 0.85 the diameter of the lesion had 81% sensitivity, 58% specificity, 24% positive predictive value and 95% negative predictive value.
Our study confirms that small testicular masses are often benign and do not always require radical orchiectomy. Preoperative ultrasound can assess lesion size and the smaller the nodule, the less likely that it is malignant. Therefore, we suggest a stepwise approach to small testicular masses, including tumorectomy, frozen section examination and radical orchiectomy or testis sparing surgery according to frozen section examination results.
Purpose
To evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) in predicting prostate cancer (PCa) and clinically significant PCa (csPCa) ...on prostate biopsies among men scheduled for initial prostate biopsy.
Methods
In this single-center prospective study, 52 men scheduled for initial prostate biopsy, based on elevated total PSA level (> 3 ng/ml) or abnormal digital rectal examination, were consecutively included. All subjects underwent SelectMDx, PSA determination and mpMRI.
Results
SelectMDx score was positive in 94.1 and 100% of PCa and csPCa, respectively, and in only 8.6% of negative cases at biopsy. The probability for a csPCa at the SelectMDx score was significantly (
p
= 0.002) higher in csPCa (median value 52.0%) than in all PCa (median value 30.0%). SelectMDx showed slightly lower sensitivity (94.1 versus 100.0%) but higher specificity (91.4%) than total PSA (17.1%), and the same sensitivity but higher specificity than mpMRI (80.0%) in predicting PCa at biopsy. The association of SelectMDx plus mpMRI rather than PSA density (PSAD) plus mpMRI showed higher specificity (both 91.4%) compared to the association of PSA plus mpMRI (85.7%). In terms of csPCa predictive value, SelectMDx showed higher specificity (73.3%) than PSA (13.3%) and mpMRI (64.4%); as for the association of SelectMDx plus mpMRI (75.6%) versus PSA plus mpMRI (68.9%), the association of PSAD plus mpMRI showed the highest specificity (80.0%).
Conclusion
Our results of SelectMDx can be confirmed as significant but their impact on clinical practice together with a cost-effectiveness evaluation should be investigated in a larger prospective multicenter analysis.
Purpose
To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN).
Methods
302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN ...(CLOCK trial—ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared.
Results
Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm,
p
< 0.001) and RENAL score (5 vs 6,
p
< 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml,
p
= 0.7), post-operative complications rate (19% vs 26%,
p
= 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%,
p
= 0.9; transfusion rate 3.4% vs 6.3%,
p
= 0.5; re-intervention due to bleeding 1.1% vs 4%,
p
= 0.4), acute kidney injury (4% vs 6%,
p
= 0.8), and positive surgical margins (3.5% vs 8.2%,
p
= 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09–0.52,
p
= 0.008).
Conclusions
The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.
Objective
Local tumor ablation to treat small renal mass is increasing. The aim of the present study was to compare oncologic outcomes among patients with T1 renal mass treated with partial ...nephrectomy and local tumor ablation.
Methods
To reduce the inherent differences between patients undergoing laparoscopic or robot‐assisted partial nephrectomy (n = 405) and local tumor ablation (n = 137), we used a 1:1 propensity score‐matched analysis. Local tumor ablation consisted of radiofrequency ablation and cryoablation. Disease‐free survival, overall survival and other causes mortality‐free survival rates were estimated using the Kaplan–Meier method. Multivariable logistic regression and competing‐risk regression models were used to identify predictors of complications, recurrence and other causes mortality, respectively.
Results
Partial nephrectomy had higher disease‐free survival estimates, as compared with local tumor ablation (92.8% vs 80.4% at 5 years, P = 0.02), with no significant difference between radiofrequency ablation and cryoablation (P = 0.9). Ablation showed comparable overall survival estimates to partial nephrectomy (91% vs 95.8% at 5 years, P = 0.6). The 5‐year recurrence rates were 7.9% versus 23.8% for patients aged ≤70 years, and 2.5% versus 11.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively; the 5‐year other causes mortality rates were 0% and 2.2% for patients treated with partial nephrectomy and ablation aged ≤70 years, and 3% versus 10.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively. At multivariable analysis, ablation was associated with fewer complications (odds ratio 0.41; P = 0.01). At competing risks analysis, age (hazard ratio 0.96) and ablation (hazard ratio 4.56) were independent predictors of disease recurrence (all P ≤ 0.008).
Conclusions
Local tumor ablation showed a higher risk of recurrence and lower risk of complications compared with partial nephrectomy, with comparable overall survival rates.
Purpose
The conventional imaging flowchart for prostate cancer (PCa) staging may fail in correctly detecting lymph node metastases (LNM). Pelvic lymph node dissection (PLND) represents the only ...reliable method, although invasive. A new amino acid PET compound,
18
F-fluciclovine, was recently authorized in suspected PCa recurrence but not yet included in the standard staging work-up of primary PCa. A prospective monocentric study was designed to evaluate
18
F-fluciclovine PET/CT diagnostic performance for preoperative LN staging in primary high-risk PCa.
Methods
Consecutive patients (pts) with biopsy-proven PCa, standard staging (including
11
Ccholine PET/CT), eligible for PLND, were enrolled to undergo an investigational
18
F-fluciclovine PET/CT. Nodal uptake higher than surrounding background was reported by at least two readers (blinded to
11
Ccholine) using a visual 5-point scale (1–2 probably negative; 4–5 probably positive; 3 equivocal); SUVmax, target-to-background (aorta—A; bone marrow—BM) ratios (TBRs), were also calculated. PET results were validated with PLND.
18
F-fluciclovine PET/CT performance using visual score and semi-quantitative indexes was analyzed both per patient and per LN anatomical region, compared to conventional
11
Ccholine and clinical predictive factors (to note that diagnostic performance of
18
F-fluciclovine was explored for LNM but not examined for intrapelvic or extrapelvic M1 lesions).
Results
Overall, 94 pts underwent
18
F-fluciclovine PET/CT; 72/94 (77%) high-risk pts were included in the final analyses (22 pts excluded: 8 limited PLND; 3 intermediate-risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant hormonal therapy). Median LNM risk by Briganti nomogram was 19%. LNM confirmed on histology was 25% (18/72 pts). Overall, 1671 LN were retrieved; 45/1671 (3%) LNM detected. Per pt, median no. of removed LN was 22 (mean 23 ± 10; range 8–51), of LNM was 2 (mean 3 ± 2; range 1–10). Median LNM size was 5 mm (mean 5 ± 2.5; range 2–10). On patient-based analyses (n = 72), diagnostic performance for LNM resulted significant with
18
F-fluciclovine (AUC 0.66,
p
0.04; 50% sensitivity, 81% specificity, 47% PPV, 83% NPV, 74% accuracy), but not with
11
Ccholine (AUC 0.60,
p
0.2; 50%, 70%, 36%, 81%, and 65% respectively). Briganti nomogram (OR = 1.03,
p
= 0.04) and
18
F-fluciclovine visual score (≥ 4) (OR = 4.27,
p
= 0.02) resulted independent predictors of LNM at multivariable analyses. On region-based semi-quantitative analyses (n = 576), PET/CT performed better using TBR parameters (TBR-A similar to TBR-BM; TBR-A fluciclovine AUC 0.61,
p
0.35, vs choline AUC 0.57
p
0.54; TBR-BM fluciclovine AUC 0.61,
p
0.36, vs choline AUC 0.58,
p
0.52) rather than using absolute LN SUVmax (fluciclovine AUC 0.51,
p
0.91, vs choline AUC 0.51,
p
0.94). However, in all cases, diagnostic performance was not statistically significant for LNM detection, although slightly in favor of the experimental tracer
18
F-fluciclovine for each parameter. On the contrary, visual interpretation significantly outperformed PET semi-quantitative parameters (choline and fluciclovine: AUC 0.65 and 0.64 respectively;
p
0.03) and represents an independent predictive factor of LNM with both tracers, in particular
18
F-fluciclovine (OR = 8.70,
p
0.002, vs OR = 3.98,
p
= 0.03).
Conclusion
In high-risk primary PCa,
18
F-fluciclovine demonstrates some advantages compared with
11
Ccholine but sensitivity for metastatic LN detection is still inadequate compared to PLND. Visual (combined morphological and functional), compared to semi-quantitative assessment, is promising but relies mainly on readers’ experience rather than on unquestionable LN avidity.
Trial registration
EudraCT number: 2014–003,165-15
Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant ...PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4-5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 score followed by a positive SelectMDx.
Background
Aim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive ...partial nephrectomy (MI-PN).
Material and methods
All consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score.
Results
1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%);
p
= 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%);
p
= 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables),
p
< 0.0001.
Conclusions
The results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP.
Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely ...used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy.
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