REVIEW


New Molecular Markers for Prostate Cancer Diagnosis

Mahan Amiri, Leila Asadi Samani, Amir H Kashi, Nazanin Khadem, Seyed Amir Mohsen Ziaee, Seyed javad Mowla

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 1-13
https://doi.org/10.22037/uj.v20i.7687

Purpose: Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth leading cause of
cancer death among men worldwide. Biomarkers are an important tool in the early detection of PCa. Prostate-specific antigen (PSA) is one of the oldest biomarkers for the early detection of PCa. Digital rectal exam (DRE) is
another screening test for PCa detection, which is considered as an irritating experience for patients. Biopsy is still
the most reliable method for PCa diagnosis; however, patients are prone to complications. Therefore, developing
non-invasive and accurate methods for PCa screening seems urgent to avoid unnecessary biopsies. There has been
remarkable development in PCa molecular biomarkers discovery, largely through progress in omics technologies.
Due to the many benefits of liquid biopsies, a significant set of PCa diagnostic kits have been developed using urine
samples. Despite the unique benefits of these kits, there are still many challenges to their widespread use in clinics.
Here, we have reviewed the latest developments of PCa biomarkers in liquid biopsies.
Methods: Literature on biomarkers for diagnosis of PCa was reviewed during the past two decades.
Results: PSA, PHI, PCA3, and 4K score are among the commonly used markers for PCa diagnosis which have
been used over a long-moderate length of time with multiple studies on their performance. We performed a review
of their performance. Newer markers are among RNA and DNA markers. Multiple non-coding RNAs (mi-RNAs)
were reviewed and their performance on Pca diagnosis was reviewed. Long noncoding RNAs (Lnc RNAs) including
PlncRNA-1, HOTAIR, SchLAP-1, MALAT1, MEG3, and PRCAT17.3 were summarized. mRNA markers
including TMPRSS2:ERG, and HOXC6 were presented. DNA-based markers including PTEN, HOXB13, and
BRCA2 were reviewed. Finally, the use of CircRNAs was reviewed for PCa diagnosis.
Conclusion: Many reviewed RNA-based biomarkers have promising results in the diagnosis of PCa.

Purpose: To compare the effects of RALP and LRP on health-related QoL following radical prostatectomy, focusing
on studies performed via validated QoL questionnaires measuring particularly general health-related QoL.

Material and Methods: A systematic search was conducted using Web of Science, PubMed (MEDLINE) on 15
January 2023 with the following search terms solely or in combination: "robotic radical prostatectomy", "laparoscopic radical prostatectomy," and "quality of life". After retrieving the titles and abstracts of selected articles, the full texts of related articles were screened.

Results: After full-text evaluation, among 185 articles, 23 articles were found eligible for inclusion. Hoze et al.
reported that the global health status at the 12th month of the surgery was almost the same in both groups according to EORTC- QLQ-C30 scores (76.3 in the RALRP group vs. 76.1 in the LRP group). Wang et al. reported a
75 point of EORTC-QOL-C30 global health status ten years after LRP. Wyler et al. found that the 1-3 month
EORTC-QLQ-C30 global health score was significantly worser than the baseline score, 65.3±18.3 vs. 77.2±18.2;
however, it returned to baseline in 13-24 months (77.7±16.8) even proceed baseline score in experienced hands at
49-58 months follow up, 78.2±17.8 vs. 85.3±15.5. The frequently used patient-reported quality of life questionnaire
following RALRP was EORTC-QLQ.

Conclusion: Both robotic-assisted and laparoscopic radical prostatectomy are valid treatment options to achieve
a good quality of life following surgery. The intermediate and long-term results in regard to QoL are comparable
between the two procedures. RALRP might be superior to LRP in terms of immediate health-related quality of life,
which might contribute to early recovery of urinary function.

Prostate Volume is A Predictor of Gleason Score Upgrading after Radical Prostatectomy in Low-Risk Prostate Cancer: A Systematic Review and Meta-analysis

Qianming Zou, Jiadong Cao, Zhiqiang Chen, Shusheng Wang, Chiming Gu, Siyi Li, Songtao Xiang

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 20-28
https://doi.org/10.22037/uj.v20i.7796

Purpose: The prediction of Gleason score (GS) upgrading in patients diagnosed with low-risk prostate cancer is
particularly important when opting for active surveillance (AS). Thus, we aimed to explore the association between
prostate volume and GS upgrading after radical prostatectomy in low-risk prostate cancer through a meta-analysis.
Methods: Multiple databases (Web of Science, MEDLINE, Embase, Scopus, and the Cochrane Library) were
searched for eligible studies regarding this issue and reporting sufficient data up to May 2023. Specific search
terms such as prostate cancer, radical prostatectomy, and prostate volume were used in our search strategy. Multivariable-adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.
Results: Twenty studies comprising 14,823 patients who underwent radical prostatectomy matched our eligibility
criteria. Moreover, GS upgrading between biopsy and surgical pathological specimens occurs in 32.2% (4,771) of
cases. The results showed that smaller prostate volume is significantly associated with GS upgrading in patients
with low-risk prostate cancer (OR = 1.08, 95% CI = 1.05–1.11; P < 0.001; I-square [I2] = 89.8%) from biopsy
to radical prostatectomy after adjusting for confounding factors. Moreover, the results of our subgroup analyses
revealed that smaller prostate volume remained a substantial risk factor of GS upgrading in the studies designed
as retrospective cohorts and case-control studies performed in America, Italy, Turkey, and China. The findings are
robust as indicated by sensitivity and meta-regression analyses.
Conclusion: Smaller prostate volume predicts clinically substantial GS upgrading in patients diagnosed with lowrisk
prostate cancer after radical prostatectomy. The intriguing findings might be helpful when management options
other than surgery are selected based on the inability to recognise the true pathological GS of patients for AS.
Further studies focus on risk-stratification and treatment planning for patients with low-grade prostate cancer are
still needed to verify our results.

ORIGINAL PAPER (ENDOUROLOGY AND STONE DISEASE)


Purpose: Three-Dimensional (3D) could help for planning and creating an optimal access route in percutaneous nephrolithotomy (PCNL) procedure by achieving a more accurate approach to the renal collecting system and stone treatment while decreasing the risk of complications. The aim of our study is to compare the efficacy of 3D imaging technique with standard fluoroscopy method as a guiding tool for renal stone location while striving to reduce intra-operative X-ray exposure in the former method.

Materials and Methods: This randomised clinical trial enrolled 48 PCNL candidates who were referred to Sina Hospital (Tehran, Iran). Participants were divided into two equal groups of intervention (3D virtual reconstruction) and control, using block randomization method. Age, sex, stone type and location, X-ray exposure during the procedure, stone access accuracy rate and the necessity of blood transfusion during surgery were taken into account.

Results: The Mean age of participants (n = 48) was 46.4 ± 4.8 years, 34 (70.8%) were male, 27 (56.3%) had partial staghorn stones and all participants had stones within the lower calyx. The radiation exposure time, stone access time and stone size were 2.99 ± 1.81 seconds, 272.3 ± 108.9 seconds and 23.06 ± 2.28 mm, respectively. In the intervention group, the accuracy rate for lower calyceal stone access was 91.5%. Also, X-ray exposure and time to stone access were significantly lower in the intervention group compared to the controls (P < 0.001).

Conclusion: We concluded that the utilization of 3D technology in the pre-operative location of renal calculi in PCNL candidates may result in a significant improvement in the accuracy and time to access the renal calculi, as well as reduction in X-ray exposure.

Medium-Term Stone Recurrence after zero-fragment transperitoneal Laparoscopic Pyelolithotomy Compared with Percutaneous Nephrolithotomy for Large Single Renal Pelvis Stones

Hamid Pakmanesh, Sohrab MohammadSalehi, Mahboubeh Mirzaei, Morteza Hashemian, Nazanin Eslami, Rayka Sharifian

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 35-39
https://doi.org/10.22037/uj.v20i.7676

Purpose: To compare medium-term stone recurrence between laparoscopic pyelolithotomy (LP) and percutaneous
nephrolithotomy (PCNL).

Material and methods: 98 patients who underwent PCNL or LP (2015-2019) for large single renal pelvis or
staghorn stones (≥ 2 cm) were selected. The stone-free rate was evaluated using a computed tomography scan at
one month and then, ultrasonography at six months intervals during the first year and annually thereafter for up to
three years. Time-to-stone recurrence was compared using the Kaplan-Meier estimate. Hazard ratio was estimated
by Cox regression.

Results: The one month stone-free rate was 93.88% in the LP group vs. 79% in the PCNL group (P = .03). The
mean overall time-to-stone recurrence was 31 (CI:24-34) months in the LP vs. 28 (CI: 23-32) in the PCNL groups
(P = .02). Cox regression analysis showed that PCNL increased the risk of stone recurrence with a hazard ratio of
2.3 (CI: 1.1 – 5.3) compared to the laparoscopy. (p = .03) In subgroup analysis, time-to-stone recurrence in those without previous history of intervention was estimated at 31 (CI: 27 to 35) months in the LP vs. 25 (CI:16 to 34) in PCNL groups (= 0.04). Subanalysis with a BMI cutoff of 25 kg/m2 showed an overall time-to-stone recurrence of 34 (CI:30 to 37) months in the LP group and 28 (CI:22 to 33) months in the PCNL group (= 0.04) in those with BMI higher than 25 kg/m2.

Conclusion: Medium-term time to stone recurrence was in favor of LP compared with PCNL for large single renal
pelvis or staghorn stones.

ORIGINAL PAPER (LAPAROSCOPIC AND ROBOTIC UROLOGY)


Efficacy of the Addition of Robot-assisted Radical Cystectomy with Extracorporeal Urinary Diversion after an Enhanced Recovery Protocol

Jun Nagayama, Akiyuki Yamamoto, Yushi Naito, Hiroki Kamikawa, Hideyuki Kanazawa, Akiyuki Asano, Norie Sho, Yasuhiro Terashima

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 40-46
https://doi.org/10.22037/uj.v20i.7752

Purpose: It is unclear if robotic radical cystectomy with extracorporeal urinary diversion (eRARC) provides additional
benefit when performed along with enhanced recovery after surgery (ERAS). We assessed the additional
efficacy of eRARC in terms of perioperative outcomes.

Materials and Methods: We retrospectively assessed 143 patients undergoing radical cystectomy with urinary
diversion between June 2010 and December 2021 at a single center. The patients were assigned to three groups:
open radical cystectomy (ORC) with conventional recovery after surgery (CRAS) [Group A], ORC with ERAS
[Group B], and eRARC with ERAS [Group C]. A propensity score-matched analysis was performed to evaluate
how ERAS and eRARC affected outcomes respectively. Meanwhile, multivariable analysis was used to detect the
predictors of prolonged length of hospital stay (LOS).

Results: The median LOS was shorter after ERAS and eRARC. In the propensity score-matched analysis, ERAS
was linked to a significantly shorter median LOS (28.0 vs. 20.0 days, P < .001), but eRARC was not associated
with a shorter LOS (19.0 vs. 17.5 days, P = .21). Neither ERAS nor eRARC were connected with a reduce in complication rate. Following multivariable analysis, ERAS was found to be independently associated with shorter LOS (OR=0.23, P < .001), but eRARC demonstrated no such correlation (OR=0.29, P = .096).

Conclusion: ERAS had strong association with shorter LOS, although eRARC did not contribute to additional
efficacy. Neither ERAS nor eRARC decreased the complication rate.

ORIGINAL PAPER(UROLOGICAL ONCOLOGY)


Comparison of Early Inguinal Lymph Node Dissection and Neoadjuvant Chemotherapy in Penile Cancer Patient with Bulky Nodal Metastasis: A Cohort Study

Syah Mirsya Warli, Jeremy Thompson Ginting, Bungaran Sihombing, Ginanda Putra Siregar, Fauriski Febrian Prapiska

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 47-51
https://doi.org/10.22037/uj.v20i.7448

Purpose: Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is
associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a
penile cancer patient with bulky lymph node.

Methods: We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent
treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients
who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were
asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient's quality of life.

Results: Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median
follow-up after primary diagnosis was 114+32 months in patients with early ILND and 52+11 months in patients
who underwent delayed lymph node dissection. Out of 5 patients who underwent early ILND, all of them survived
during follow-up, and achieved cancer-free status without residual tumor and with excellent functional outcomes
(Karnofsky 90). There was no significant difference in social function (p-value = 0.551), physical function (p-value
= 0.272), role function (p-value = 0.546), emotional function (p-value = 0.551), cognitive function (p-value =
0.453), and global health status (p-value = 0.893) between patient which treated with early ILND and Neoadjuvant
Chemotherapy. However, patients who underwent early ILND showed a relatively better clinical outcome.

Conclusion: Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more
favourable than neoadjuvant TIP chemotherapy.

ORIGINAL PAPER (PEDIATRIC UROLOGY)


Pediatric Pyeloplasty in the Poor Function Kidneys: Does Surgical Success Guarantee Improvement in Renal Function? Single-Center Experience and Review of Literature

Farzaneh Sharifiaghdas, Jalal Amini, Behzad Narouie, Hamidreza Rouientan, Mohadese Ahmadzade, Mohammad Aref Emami

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 52-56
https://doi.org/10.22037/uj.v20i.7768

Purpose: To investigate the effect of pyeloplasty in pediatric patients with poor function kidneys, focusing on the split renal function (SRF) and anteroposterior diameter (APD) of the renal pelvis.

Materials and Methods: A retrospective study included 47 pediatric patients with ureteropelvic junction obstruction (UPJO) who underwent open pyeloplasty with SRF< 20%. All patients were recruited from the Labbafinejad University Hospital center from April 2014 to October 2020. The results of preoperative ultrasonography and Diethylenetriamine pentaacetate (DTPA) scan compared with the results of the ultrasonography and DTPA scan 6 months and one year after surgery. Finally, Wilcoxon signed-rank test was used to test differences the SPSS (version 25) software statistical computer package.

Results: The mean age of participants was 1.5 years. There were 34 cases with SRF between 10% and 20%, and 13 cases with SRF < 10%. The findings showed that pyeloplasty for UPJO leads to a significant improvement in renal function in poorly functioning renal units with 10% ≤ SRF < 20%. Although improvement in renal function occurred in the group with SRF of less than 10%, it was not statistically significant. The APD in both groups was statistically significantly improved. No correlation between genders and outcomes was found.

Conclusion: Poorly functioning renal unit (SRF < 20%) can show functional improvement after the pyeloplasty.

UNCLASSIFIED


An in-silico Approach for Recognition of Long non-coding RNA-Associated Competing Endogenous RNA Axes in Prostate Cancer

Mohammad Taheri, Arash Safarzadeh, Soudeh Ghafouri-Fard, Aria Baniahmad

Urology Journal, Vol. 21 No. 01 (2024), 28 Esfand 2024, Page 57-73
https://doi.org/10.22037/uj.v20i.7650

Purpose: Prostate cancer is among the most central sources of cancer-related mortalities. In order to find novel candidates for therapeutic strategies in this kind of cancer, we developed an in-silico method for identification of competing endogenous RNA network.

Methods: According to the microarray data analyses between prostate tumor and normal specimens, we attained 1312 differentially expressed (DE)mRNAs, including 778 down-regulated DEmRNAs (such as CXCL13 and BMP5) and 584 up-regulated DEmRNAs (such as OR51E2 and LUZP2), 39 DElncRNAs, including 10 down-regulated DElncRNAs (such as UBXN10-AS1 and FENDRR) and 29 up-regulated DElncRNAs (such as PCA3 and LINC00992) and 10 DEmiRNAs, including 2 down-regulated DEmiRNAs (such as MIR675 and MIR1908) and 8 up-regulated DEmiRNAs (such as MIR6773 and MIR4683).

Results: We constructed the ceRNA network between these transcripts. We also evaluated the related signaling pathways and the significance of these RNAs in prediction of survival of patients with prostate cancer.

Conclusion: This study provides novel candidates for construction of specific treatment routes for prostate cancer.