Indian Journal of Urology
EDITORIAL
Year
: 2023  |  Volume : 39  |  Issue : 1  |  Page : 3--6

Round up


Swarnendu Mandal 
 Department of Urology, AIIMS, Bhubaneswar, Odisha, India

Correspondence Address:
Swarnendu Mandal
Department of Urology, AIIMS, Bhubaneswar, Odisha
India




How to cite this article:
Mandal S. Round up.Indian J Urol 2023;39:3-6


How to cite this URL:
Mandal S. Round up. Indian J Urol [serial online] 2023 [cited 2023 Jan 28 ];39:3-6
Available from: https://www.indianjurol.com/text.asp?2023/39/1/3/365905


Full Text

 Oncological Outcomes in Muscle-Invasive Bladder Cancer Patients with Positive Surgical Margins Following Radical Cystectomy



Positive surgical margins (PSMs) of up to 4%–15% are seen after radical cystectomy (RC) which negatively affects the oncological outcomes.[1] In a recent multicenter retrospective cohort study, 394 muscle-invasive bladder cancer (MIBC) patients with PSMs following RC were assessed for locoregional recurrence-free survival (LRFS), metastatic-free survival, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).[2]

The pathological stage was pT3 in 33%, pT4 in 52%, and node positive (pN+) in 38%. The distribution of PSMs was 72%, 16%, 18%, and 16% for soft-tissue PSMs, urethral PSMs, ureteral PSMs, and multifocal PSMs, respectively. At a median follow-up of 44 months, the median LRFS, MRFS, RFS, CSS, and OS were 14, 12, 10, 23, and 16 months, respectively. On multivariate regression analysis, pT3, pT4, pN+, and multifocal PSMs were independent predictors of survival outcomes. The authors confirmed poor oncological outcomes associated with PSMs, with up to 50% recurrence and deaths within a year of surgery.

 Comparison Between Biparametric and Multiparametric Magnetic Resonance Imaging in Predicting Muscle Invasion by Bladder Cancer Based on the VI-RADS



The authors[3] retrospectively analyzed the preoperative magnetic resonance imaging (MRI) of 357 patients with BCa (multiparametric MRI-(mpMRI) in 257 and biparametric MRI-(bpMRI) in 100). Using Vesicle Imaging Reporting and Data System (VIRADS), two radiologists assessed all the scans. Based on histopathology, the diagnostic value of VIRADS for predicting muscle invasion was investigated. With a VI-RADS score of ≥3, both groups performed optimally. BpMRI showed the equivalent diagnostic performance to mpMRI. Both readers had a very high inter-reader agreement. This study revealed that bpMRI has the equivalent diagnostic performance to mpMRI, and the contrast sequence is not always needed to predict muscle invasion.

 Clinical Utility of Intraductal Carcinoma of the Prostate in Treatment Selection for Metastatic Hormone-Sensitive Prostate Cancer



Naito et al.[4] attempted to investigate the association between the presence of intraductal carcinoma of the prostate (IDC-P) and response to androgen receptor axis-targeted agents (ARATs) in metastatic hormone-sensitive prostate cancer (mHSPC).

The study is a retrospective analysis of 359 patients with mHSPC. The response to first-line treatments, including ARAT (n = 100) and conventional therapy (androgen deprivation therapy only; n = 218), were compared for OS and progression-free survival (PFS2) with reference to the presence of IDC-P. The time from the diagnosis of mHSPC to the onset of the disease on second-line therapy or until death was designated as PFS2. The results showed a 70%–80% prevalence of IDC-P in patients with mHSPC. However, the OS and PFS2 of IDC-P-positive patients in the propensity score-matched cohort were considerably longer in the ARAT group than in the conventional group (P < 0.001). Thus, the presence of IDC-P may be a valid marker for the need for ARAT as first-line therapy.

 Beta-Blocker Use and Urothelial Bladder Cancer Survival: A Swedish Register-Based Cohort Study



B-adrenergic blockers have been shown to prolong cancer survival in breast and pancreatic cancer.[5],[6] Urothelial cancer has shown significant overexpression of b-adrenergic receptors relative to the normal nondiseased urothelium.

The Swedish Cancer Register identified 16,669 bladder cancer (BCa) patients aged ≥18 years from 2006 to 2014 until December 2015.[7] Patients who took a b-blocker within 90 days of cancer diagnosis were considered exposed. The association between b-blockers use and bladder cancer-specific mortality (BCSM), the primary outcome, and all-cause mortality were calculated after adjusting for sociodemographic variables, tumor characteristics, comorbidities, other drugs, and surgical procedures.

B-blockers reduced BCSM ([HR] 0.88 [95% confidence interval (CI) 0.81–0.96]). In locally advanced/metastatic urothelial BCa patients, nonselective b-blockers lowered BCSM, but not selective. Thus, a low-cost, nonselective b-blocker could be an additional armamentarium in improving survival.

 Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Nonmuscle-Invasive Bladder Cancer



Intravesical sequential therapy with gemcitabine and docetaxel (Gem/Doce) is an accepted treatment both in patients with Bacillus Calmette–Guérin (BCG) failure and who are BCG naïve in the era of BCG shortage.[8],[9] Intravesical valrubicin monotherapy showed dismal outcomes.[10]

In this retrospective analysis, recurrent non-NMIBC (NMIBC) patients previously treated with BCG, Gem/Doce, or both were given sequential intravesical valrubicin and docetaxel (Val/Doce).[11] Each cycle comprised 800 mg valrubicin followed by 37.5 mg docetaxel. Induction comprised 6 weekly installations, and maintenance once monthly installations for up to 24 months. Seventy-five patients were followed up for a median period of 21 months. At 2 years, the RFS of low-grade and high-grade disease was 73% and 38%, respectively, and the PFS was 82%. Eighty-four percent of patients could avoid cystectomy at 2 years.

This is a potential salvage therapy option in patients who would otherwise undergo cystectomy.

 Removal of Small, Asymptomatic Kidney Stones, and Incidence of Relapse



The surgical removal of small (≤6 mm), asymptomatic stones is ambiguous, with no clear-cut recommendations. The only prospective trial studied the role of shock wave lithotripsy in this setting and favored observation.[12]

This multicenter, randomized controlled trial (1;1) enrolled patients undergoing endoscopic removal of ureteral or contralateral kidney stones. The remaining small, asymptomatic stones were removed in 38 patients (treatment group) and were not removed in 35 patients (control group/observational group).[13]

All were followed for 5 years. Sixteen percent of the treatment group relapsed in the form of an emergency visit, surgery, or an increase in the size of the secondary stone, as opposed to 63% in the observation group. A median additional duration of 25–30 min was required for the endoscopic removal of the secondary stones in the same sitting in the treatment group, with no significant increase in perioperative complications.

With the advent of new technologies, simultaneous endoscopic removal of secondary stones can decrease long-term morbidity without compromising perioperative outcomes.

 Laparoscopic Palomo Surgery Versus Scrotal Antegrade Sclerotherapy in Adolescent Varicocele: A Randomized Control Trial



Patients with left Grade-3 varicocele indicated for surgery were prospectively enrolled, with their respective contralateral normal testes taken as controls.[14] Patients undergoing scrotal antegrade sclerotherapy (SAS, n = 57) and laparoscopic Palomo surgery (LPS, n = 56) were enrolled. At the 12-month follow-up, there was no statistically significant difference in clinical recurrences between the two groups (SAS = 5.3% vs. LPS = 5.4%, P > 0.05, noninferiority test). The mean testicular volume difference between the treatment and control testes reduced from −23% to −8.1% in SAS (P < 0.001) and −19% to −9.3% in LPS (P < 0.001) at the 12-month follow-up. There was no postoperative hydrocele in SAS compared to 7 in LPS (0% vs. 13%, P = 0.006).

SAS is not inferior to LPS in terms of clinical recurrence rate and with significantly less postoperative hydrocele.

 Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy (RC) and Nephroureterectomy



Simultaneous RC and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. The authors compared the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone.[15]

A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in the length of stay, estimated blood loss, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35–0.97, P = 0.04) was significantly better for patients undergoing RC alone, whereas no significant difference was noted in recurrence-free survival (HR 0.65, 0.34–1.24) and cancer-specific survival (HR 0.58, CI 0.31–1.08, P = 0.08). Perioperative outcomes between the groups did not differ significantly.

 Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor



In this randomized control trial (RCT), Lee et al. assessed the efficacy and safety of intravesical mitomycin-C (Iv-MMC) before transurethral resection of bladder tumor (TURBT) in patients with NMIBC.[16]

Participants were randomly assigned to receive two doses of Iv-MMC (40 mg/20 mL) 1 day and 4 h before TURBT (n = 49) or no treatment (n = 50). The 1-year RFS rate was 97% and 89% for the intervention and control groups, respectively. Neoadjuvant Iv-MMC resulted in a 63% reduction in relative recurrence risk. Disease progression occurred in three patients in the control group but not in the intervention group. Neoadjuvant Iv-MMC is well tolerated, with few local or grade 1/2 adverse effects. Thus, two doses of neoadjuvant Iv-MMC are safe and efficacious in preventing NMIBC recurrence and progression following TURBT.

 Gene Therapy for Refractory Overactive Bladder



There is a pressing need for newer treatment modalities for refractory overactive bladder (OAB). URO-902, a plasmid vector that encodes the subunit of the large-conductance Ca2+-activated K + channel, has been employed by scientists to investigate gene therapy in the treatment of bladder overactivity.

Female OAB patients who had failed to respond to oral medicines were included in a phase-2 multicenter, double-blind, randomized experiment where URO-902 injections of 24 mg and 48 mg were compared with a placebo.[17] At week 12 interim analysis, URO-902 24 mg and 48 mg showed improvement compared to placebo in the mean daily micturition (−2.5 and −3.0 vs. −1.0), urgency episodes (−2.4 and −3.4 vs. −1.2), and OAB questionnaire symptom score (−24.1 and − 25.3 vs. −11.2). However, there was no difference in UUI episodes (−2.4 and −2.6 vs. −2.3). Gene therapy with URO-902 is a promising prospective therapy for OAB, which requires further investigation.

 Targeting Germline Precursors to Induce HIV Broadly Neutralizing Antibodies



HIV, along with other viruses, expresses extreme antigenic diversities, which makes vaccine development challenging. In this aspect, vaccines that induce broadly neutralizing antibodies (bnAbs) with prespecified genetic characteristics along with binding specificities are believed to be promising.[18] With robust preclinical data supporting the efficacy of a vaccine immunogen eOD-GT8, Leggat et al. conducted a phase-1 clinical trial in 48 participants and evaluated the safety and immune response of the drug.[19] Each participant received two doses of the placebo, low-dose, or high-dose vaccine, spaced 8 weeks apart. Immune cells from the blood and lymph nodes were collected, and epitope-specific B-cell sorting and B-cell receptor sequencing were carried out. In 97% (35 of 36) of participants, the vaccine-evoked HIV VRC01-class bnAb responses and a substantial gain in the somatic hypermutation of the precursors of bnAbs.

The current trial supports the concept of germline targeting for bnAbs production. However, precursors for VRC01-class antibodies are highly conservative when compared to precursors targeting other HIV epitopes (which are highly promiscuous).[20],[21] Nevertheless, this study stands as a proof of concept for establishing and developing vaccine regimens that can boost the production of VRC01-class bnAbs against HIV and other pathogens.

 Effectiveness of Intrarectal Povidone-Iodine Cleansing Plus Formalin Disinfection of the Needle Tip in Decreasing Infectious Complications After Transrectal Prostate Biopsy



The transperineal prostatic biopsy is preferred over the transrectal ultrasound-guided prostate biopsy (TRUS-Bx) route due to its higher infectious complications.[22]

This single-center RCT randomized 1234 patients undergoing TRUS-Bx to receive preprocedure rectal cleansing with 10% povidone-iodine and used a formalin-dipped needle in the intervention arm.[23] Both the treatment groups received 3 days of ciprofloxacin starting one night before. Infectious complications in terms of fever, UTI, or sepsis were significantly decreased in the intervention arm (3.9% vs. 6.4%, P = 0.49). Urine culture positivity following the procedure was also lower (5.2% vs. 9%, P = 0.15). It was interesting to note that 95% of the positive cultures were quinolone resistant. This simple, inexpensive practice can be adopted to bring down infectious complications following TRUS-Bx.

Financial support and sponsorship: Nil.

Conflicts of interest: There are no conflicts of interest.

References

1Claps F, van de Kamp MW, Mayr R, Bostrom PJ, Boormans JL, Eckstein M, et al. Risk factors associated with positive surgical margins' location at radical cystectomy and their impact on bladder cancer survival. World J Urol 2021;39:4363-71.
2Marcq G, Afferi L, Neuzillet Y, Nykopp T, Voskuilen CS, Furrer MA, et al. Oncological outcomes for patients harboring positive surgical margins following radical cystectomy for muscle-invasive bladder cancer: A retrospective multicentric study on behalf of the YAU Urothelial Group. Cancers (Basel) 2022;14:5740.
3Noh TI, Shim JS, Kang SG, Sung DJ, Cheon J, Sim KC, et al. Comparison between biparametric and multiparametric MRI in predicting muscle invasion by bladder cancer based on the VI-RADS. Sci Rep 2022;12:20689.
4Naito Y, Kato M, Kawanishi H, Yamamoto A, Sakamoto F, Hirabayashi H, et al. Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer. Prostate 2022. Nov 24. doi: 10.1002/pros.24462. Epub ahead of print.
5Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: A population-based study. J Clin Oncol 2011;29:2635-44.
6Udumyan R, Montgomery S, Fang F, Almroth H, Valdimarsdottir U, Ekbom A, et al. Beta-blocker drug use and survival among patients with pancreatic adenocarcinoma. Cancer Res 2017;77:3700-7.
7Udumyan R, Botteri E, Jerlstrom T, Montgomery S, Smedby KE, Fall K. Beta-blocker use and urothelial bladder cancer survival: A Swedish register-based cohort study. Acta Oncol 2022;61:922-30.
8Steinberg RL, Thomas LJ, Brooks N, Mott SL, Vitale A, Crump T, et al. Multi-institution evaluation of sequential gemcitabine and docetaxel as rescue therapy for nonmuscle invasive bladder cancer. J Urol 2020;203:902-9.
9McElree IM, Steinberg RL, Martin AC, Richards J, Mott SL, Gellhaus PT, et al. Sequential intravesical gemcitabine and docetaxel for bacillus calmette-guérin-naïve high-risk nonmuscle-invasive bladder cancer. J Urol 2022;208:589-99.
10Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol 2000;163:761-7.
11McElree IM, Packiam VT, Steinberg RL, Mott SL, Gellhaus PT, Nepple KG, et al. Sequential intravesical valrubicin and docetaxel for the salvage treatment of non-muscle-invasive bladder cancer. J Urol 2022;208:969-77.
12Keeley FX Jr., Tilling K, Elves A, Menezes P, Wills M, Rao N, et al. Preliminary results of a randomized controlled trial of prophylactic shock wave lithotripsy for small asymptomatic renal calyceal stones. BJU Int 2001;87:1-8.
13Sorensen MD, Harper JD, Borofsky MS, Hameed TA, Smoot KJ, Burke BH, et al. Removal of small, asymptomatic kidney stones and incidence of relapse. N Engl J Med 2022;387:506-13.
14Chung KL, Hung JW, Yam FS, Chao NS, Li DC, Leung MW. Prospective randomized controlled trial comparing laparoscopic palomo surgery versus scrotal antegrade sclerotherapy in adolescent varicocele. J Urol 2022:101097JU0000000000003087. Dec 8:101097JU0000000000003087. doi: 10.1097/JU.0000000000003087. Epub ahead of print
15Britton CJ, Gottlich HC, Tarrell RF, Thapa P, Joyce DD, Shah PH, et al. Perioperative and oncologic outcomes associated with simultaneous radical cystectomy and nephroureterectomy. Urology 2022;S0090-6. Nov 25:S0090-4295(22)00973-6. doi: 10.1016/j.urology.2022.09.039. Epub ahead of print
16Lee HW, Lee HH, Park EY, Park WS, Kim SH, Joung JY, et al. Clinical efficacy of neoadjuvant intravesical mitomycin-C therapy immediately before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer: Preliminary results of a prospective, randomized phase II study. J Urol 2023;209:131-9.
17Peters K, Enemchukwu E, Kalota S, Robertson K, Greene H, Badger H, et al. Efficacy and safety of a novel gene therapy (Uro-902; Pvax/Hslo) in female patients with overactive bladder syndrome and urgency urinary incontinence: Results from a phase 2a trial. Continence 2022;2:100196.
18Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N Engl J Med 2021;384:1003-14.
19Leggat DJ, Cohen KW, Willis JR, Fulp WJ, deCamp AC, Kalyuzhniy O, et al. Vaccination induces HIV broadly neutralizing antibody precursors in humans. Science 2022;378:eadd6502.
20Williams WB, Wiehe K, Saunders KO, Haynes BF. Strategies for induction of HIV-1 envelope-reactive broadly neutralizing antibodies. J Int AIDS Soc 2021;24 Suppl 7:e25831.
21Moore PL. Triggering rare HIV antibodies by vaccination. Science 2022;378:949-50.
22EAU Guidelines on Prostate Cancer – Diagnostic Evaluation – Uroweb. Uroweb – European Association of Urology. Available from: https://uroweb.org/guidelines/prostate-cancer/chapter/diagnostic- evaluation. [Last accessed on 2022 Dec 16].
23Pontes-Junior J, Freire TM, Pugliesi FG, de Moura Costa FM, de Souza VM, Galucci FP, et al. Effectiveness of intrarectal povidone-iodine cleansing plus formalin disinfection of the needle tip in decreasing infectious complications after transrectal prostate biopsy: A Randomized Controlled Trial. J Urol 2022;208:1194-202.