Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Urinary Bladder Neck Obstruction

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Urethral Obstruction

Urethral Diseases

Urologic Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Patients with low-risk prostate cancer who were elected for active surveillance protocol will have only medical treatment for control of their lower urinary tract symptoms secondary to bladder outlet obstruction

Patients with low-risk prostate cancer who were elected for active surveillance protocol will be offered anatomical endoscopic enucleation of the prostate for control of their lower urinary tract symptoms secondary to bladder outlet obstruction

Transurethral endoscopic enucleation of the prostate adenoma

Anatomical Endoscpic enucleation of the Prostate

Ahmed Elshal, MD

We will compare oncological and functional outcomes of anatomical endoscopic enucleation of the prostate (AEEP) versus continued medical treatment in low-risk prostate cancer patients for whom an active surveillance protocol was selected.

Prostate cancer is the most common cancer in men; in 2018 1,276,106 new cases of prostate cancer were reported worldwide (1).

The diagnosis of prostate cancer is based on the microscopic evaluation of prostate tissue obtained via needle biopsy.

The International Society of Urological Pathology (ISUP) Consensus system assigns new Grade Groups from 1 to 5, derived from the Gleason score (2).

Clinicians have stratified the diagnosis into low, intermediate, and high-risk disease based on the sum of Gleason patterns, prostate specific antigen (PSA) level, and clinical stage (3).

Recently The National Comprehensive Cancer Network risk stratification uses a 5-tier system by adding very low- and very high- as a subdivision of the low- and high-risk groups (4).

Men diagnosed with localized disease (defined as no regional lymph nodes or distant metastases) have 3 primary options: expectant management, surgery and radiation.

Expectant management (monitoring for prostate cancer progression while not undergoing definitive therapy) consists of watchful waiting and active surveillance (5).

According to The Prostate Testing for Cancer and Treatment (ProtecT) trial which randomized 1643 localized prostate cancer men to active monitoring, surgery, or radiation. At 120 months, ProtecT found that 1.5% of patients on active monitoring died from prostate cancer, which did not differ significantly from the 0.9% after surgery or the 0.7% after radiation (6).

The use of active surveillance (AS) for men with low-risk prostate cancer (PCa) is well established, although the criteria for admission to a protocol vary according to the institution. (7-9) Men with significantly enlarged prostates (\>100 g) may be assigned a high-risk category when their prostate-specific antigen (PSA) rises above 10 ng/ml, although there is evidence AS is safe in this population. (10) In the presence of lower urinary tract symptoms (LUTS), men with significantly enlarged prostates often undergo radical prostatectomy (RP) to treat PCa and coexisting LUTS. This approach, which prioritizes oncologic control, may increase surgical morbidity for patients who otherwise might continue AS after an outlet procedure to address their LUTS.

The use of holmium laser enucleation of the prostate (HoLEP) for the management of LUTS in men with significantly enlarged prostates and coexisting low-risk PCa has not been prospectively studied. HoLEP has proven to be a safe and effective treatment for men with LUTS. (11) Incidental detection of malignancy at the time of HoLEP ranges from 5% to 13% in men without a prior diagnosis of PCa, and there is evidence PSA has improved sensitivity for cancer progression in the post-HoLEP setting. (12-15) The management of T1a-b PCa incidentally discovered after transurethral resection of prostate (TURP) has been well documented with AS recommended for most patients. (16-18) However, the management of men with known low-risk PCa, clinically significant LUTS, and significantly enlarged prostates remains underexplored.

Herein, we prospectively assess patients with low-risk PCa on AS who underwent AEEP for clinically significant LUTS and enlarged prostate gland size.

Our study focuses on functional and oncologic outcomes.

Transurethral Prostate Enucleation in Surveillance Protocol for Low Risk Prostate Cancer

Anatomical Endoscopic Enucleation of the Prostate for Treatment of Bladder Outlet Obstruction in Patients With Low-risk Prostate Cancer on Surveillance Protocol, Prospective Assessment of Functional and Oncological Outcome

changes of PSA level from baseline to one year follow up following active treatment

cancer progression as depicted by multiparametric MRI

improvement of urine flow parameters as depicted by peak flow rate (ml/sec)

improvement of urinary symptoms as depicted by symptom score (International prostate symptom score)

PSA, Radiological and grade progression whenever biopsy is indicated

Mansoura University

A. Professor of Urology

Patients fulfilling inclusion criteria undergo focal treatment with Trinity-guided Katty device

Microwave ablation with TATO3 generator (Katty system) under guidance of ultrasound/mpMRI fusion image device Trinity

Katty focal therapy

Marco Oderda, MD, PhD

Focal therapy (FT) for prostate cancer (PCa) is an interesting therapeutic option for localized disease with a favorable low- to intermediate-risk profile. The aim of this approach is to offer a personalized and less aggressive treatment as compared to radical treatments such as radical prostatectomy (RP) or primary radiation therapy, reducing functional morbidity while maintaining oncologic efficiency.

FT is based on the treatment of a part of the prostate, containing the index lesion. The index lesion is identified as a single visible lesion up to 12 mm at multiparametric MRI (mpMRI), which is biopsied with a fusion biopsy obtaining a Gleason score inferior or equal to 3+4. These features allow a focal treatment aimed to ablate the area containing the tumor. In case of a concomitant presence of 1 or 2 cores of Gleason score 3+3 found at systematic biopsy and invisible to mpMRI, a strategy of surveillance will be adopted, focusing the treatment only on the index lesion (only in patients older than 70 years old). Different sources of energy have been used to date for focal therapy. Among these, has emerged a very low loss (VLL) microwave ablation system, called TATO3®, specifically developed to work with the fusion biopsy platform Koelis Trinity® that allows an accurate 3D reconstruction of the prostate, with the goal to offer a targeted treatment after a targeted biopsy. Aim of this experimental trial is to evaluate the efficacy of the Trinity®-guided TATO3® treatment in the ablation of the index lesion, together with the safety of the procedure and the short-term oncologic outcomes.

Focal therapy (FT) for prostate cancer (PCa) is an interesting therapeutic option for localized disease with a favorable low- to intermediate-risk profile. The aim of this approach is to offer a personalized and less aggressive treatment as compared to radical treatments such as radical prostatectomy (RP) or primary radiation therapy, reducing functional morbidity while maintaining oncologic efficiency.

FT is based on the treatment of a part of the prostate, containing the index lesion. Over 90% of PCa are multifocal, and unilateral disease is estimated to be present in only 20-40% of patients. Despite the multifocal nature of PCa, many affected men have just a single substantial lesion, which is called index lesion. Ohori et al determined that up to 80% of PCa volume arises through the index lesion. Clinically, vast evidence indicates that the index lesion features predict the behavior of the disease. Indeed, risk stratification of the index lesion predicts PCa outcomes, irrespectively from the presence of unilateral or bilateral disease, and most metastatic PCa arise from the cell clone of the index lesion. FT relies on the concept that residual PCa in the untreated area does not compromise long-term disease control, given that it falls into the criteria of active surveillance. The success of focal therapy strongly depends on the ability to detect the foci of PCa through multiparametric magnetic resonance imaging (mpMRI), which has gained a paramount role in PCa diagnosis. Clinically significant prostatic lesions have features detectable at mpMRI and can be targeted with fusion biopsies, which combine the data coming from mpMRI and transrectal ultrasound (TRUS) imaging. Data from PROMIS trial demonstrated MRI sensitivity of 93% for clinically significant cancer, and a meta-analysis by Moldovan et al showed a negative predictive value of mpMRI of 88.1%. A European consensus meeting suggested that mpMRI in combination of a systematic sampling achieves a negative predictive value of 90-95%. Bearing in mind the limitations of the mpMRI, however, to-date systematic biopsies are mandatory, to ensure the most accurate sampling possible, and any FT performed should consider a reasonable security margin.

For a successful treatment, patient selection is essential. Currently, the ideal candidates for FT should be patients harboring intermediate-risk PCa with favorable features and a limited component of Gleason score pattern 4. A 2015 consensus meeting stated that providing FT to patients with low-risk prostate cancer would represent overtreatment in men suitable for active surveillance. Furthermore, candidates for FT must have a life expectancy of more than 5 years and a WHO performance status of 0 or 1. In the last years, FT has solidly evolved from low-risk to intermediate-risk disease: since the first FT trials, more than 2700 patients have been treated, and this approach is now at the level of exploration of indications, quality control measures, and reproducibility in larger trials. In 2017, a randomized controlled trial (RCT) has shown the potential benefits of FT versus active surveillance in low-risk PCa in terms of cancer progression, secondary treatments, and negative biopsies at 2-yrs follow-up. In intermediate-risk PCa, another RCT of partial prostate ablation versus RP has completed the feasibility phase: the main study is set up, with the goal to prove the benefit of FT versus RP in terms of PCa mortality. In line with the recommendations of the 2015 consensus meeting, the investigators believe that suitable candidates for FT are those with a single small focus of Gleason score 7 (3+4) PCa, with possible limited adjunctive presence of clinically insignificant foci of Gleason score 6 (3+3) invisible to mpMRI. When speaking of FT for PCa, several energy modalities have been developed, including high-frequency ultrasound (HIFU), cryotherapy, laser interstitial thermotherapy, photodynamic therapy, irreversible electroporation, brachytherapy, and radiofrequency ablation. To date, studies were able to prove the feasibility, low morbidity profile, and satisfying short- and medium-term oncologic results of FT, mainly based on imaging and rebiopsy. Nevertheless, according to the last European Association of Urology (EAU) guidelines, FT is still considered experimental, to be offered within a clinical trial. Recently, among energy modalities has emerged also a very low loss (VLL) microwave ablation system, called TATO3®, specifically developed to work with the fusion biopsy platform Koelis Trinity® that allows an accurate 3D reconstruction of the prostate, with the goal to offer a targeted treatment after a targeted biopsy. Aim of this experimental trial is to evaluate the efficacy of the Trinity®-guided TATO3® treatment in the ablation of the index lesion, together with the safety of the procedure and the short-term oncologic outcomes.

Since the 1980s, microwaves have been widely used for the treatment of Benign Prostatic Hyperplasia (BPH). Low intensity energy is applied to the entire organ to reduce the volume of the gland. Several studies have shown the safety of microwaves propagation through the prostate with transurethral, transperineal and transrectal accesses, while variable results have been achieved in terms of prostate volume reduction.

The treatment of PCa by microwaves requires the use of higher energy as compared to BPH treatment, in order to irreversibly denature tumor cells. A phase I/II clinical has been led since 1998 to investigate the safety and efficacy of transperineal microwave therapy for recurrent PCa following external beam radiation therapy. A preliminary result on 25 patients has shown a very low complication rate following the treatment, and good oncological results. Six months after the treatment, 64% of the biopsy result were negative. On the last update of 2004 with 41 patients enrolled, no serious complications were observed as a result of the procedure and, although mild continence problems were encountered, these were generally temporary.

TATO3® VLL microwave ablation system represents the last evolution in the field of microwave treatment for PCa. Following dry lab testing, it has been experimented in the animal setting on dogs. More recently, it has been used at Hôpital Cochin, Paris in the setting of clinical study, where preliminary results on 10 patients with low risk PCa showed an excellent safety profile of targeted focal microwave treatment for the ablation of index tumor. Final results are awaited this summer. Another study is ongoing in at Erasme Hospital, Brussels, treating patients already scheduled for radical prostatectomy, with the aim of examining the extension of the treated area and confirming the absence of cancerous cells. To-date, the treatment is well tolerated and efficacious.

Since 2015, the investigators have acquired a significant expertise in the field of prostate fusion biopsies, achieving outstanding cancer detection rates and improving the risk stratification of newly diagnosed PCa. This expertise has been gained using different platforms in commerce, from the Koelis Urostation® to the most recent Koelis Trinity®, and the investigators have reported the outcomes of these fusion biopsies on a multicentric series of more than 2.000 patients, the largest series of fusion biopsies ever published in the literature. The natural step forward would be the implementation of the Koelis bioptic platform with the possibility of delivering a focal treatment to the foci of PCa, which can be achieved with TATO3® microwave ablation system, minimizing side effects while maintaining cancer control.

Targeted Microwave Focal Therapy

Safety and Efficacy of a Novel 3D Cartography-based Targeted Microwave Focal Therapy Device in Men With Localized Low to Intermediate-risk Prostate Cancer

absence of tumor at the site of treatment in the repeated targeted biopsies at 6 months.

absence of tumor Gleason score pattern 4 at the site of treatment in the repeated targeted biopsies at 6 months

change in the functional score IPSS (International Prostate Symptom Score, from 0 (best) to 35 (worse)) 1 week, 1 month, 3 months and 6 months after the treatment, as compared to the basal score before focal therapy

change in the functional score IIEF-5 (International International Index of Erectile Function-5 score, from 5 (worse) to 25 (best)) 1 week, 1 month, 3 months and 6 months after the treatment, as compared to the basal score before focal therapy

Koelis

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Principal Investigator

Symptoms and General Pathology

Disease Progression

Yeong-Shiau Pu, PhD

Chung-Hsin Chen, PhD

In Taiwan, about 70% of new incident prostate cancer patients have localized disease. Most patients were detected by PSA screening. Among them, many had low-risk PC, which is very likely latent in nature, progresses slowly, and rarely leads to death. Most patients died of other causes, such as other cancers, cardiovascular diseases, and diabetes mellitus. Many guidelines recommend that active surveillance (AS) or watchful waiting (WW) is a good option for low risk patients to avoid overtreatment-related complications. However, 30% of patients on AS will finally need definitive treatments due to disease progression within 10 years. We hypothesize that there are differential gene expressions between progressive and non-progressive tumors. If we can identify key genes or pathways that are responsible for progression of low risk PC to higher risk diseases, PC progression could be reduced substantially by regulating these genes or pathways and maintain long-term cancer latency to control non-metastatic PC. In light of the high prevalence rate of latent PC in adult men, the strategy is in fact the best strategy for preventing clinical PC.

At the Department of Urology, NTUH, we have established a largest Chinese AS/WW cohort, which were prospectively collected since 2013. There were already 280 AS and 100 WW patients. Most AS patients have undergone serial prostate re-biopsies every 1 to 2 years, which is actually our cutting edge in the field. 87 men had at least twice biopsies at our hospital (mean interval 15 months). 26 of them showed pathological progression (Group As) who have been treated aggressively. The other 61 men had no progression even after multiple biopsies (Group Bs). So, we may compare the genetic changes in each subject in Group A to reveal genetic changes responsible for progression. We can also compare baseline expressions between Group A and B to predict progression. We also can correlate genetic alterations in Group A with cancer phenotypes and short-term post-treatment outcomes.

Here are the four Specific Aims:

Aim-1. To investigate the role of known genes or pathways in mediating progression from low risk to higher risk by using serial biopsy paraffin embedded tissue blocks from our AS patients. These known genes/pathways are selected from published reports, which are found to be related to progression from low to higher grade PC, such as Ki-67, PTEN loss, and chromosome 8 alterations.

Aim-2. There was only one cDNA microarray gene bank (GSE37199) published in the literature (Lancet Oncol. 2012; 13:1114) that was associated with differential expression between AS and mCRPC cohorts. We will proceed with the Gene Set Enrichment Analysis (GSEA) to identify more potential genes or pathways that have NOT been specifically demonstrated relating to AS progression. These new genes or pathways will then be studied in Aim-1.

Aim-3. We will perform global cDNA microarray sing non-cancer part of the serial biopsy paraffin tissue blocks from our AS cohort, followed by GSEA to reveal differential gene expression between Group A and B patients. Hopefully we can identify genes/pathways that are related to progression of low risk or latent PC in Taiwanese.

Aim-4. To conduct multivariate analyses considering not only key genetic alterations but also multiple clinicopathological parameters to build up a model predicting progression from low to higher risk PC.

In fact, the only one published study (Lancet Oncol. 2012;13:1114) was to reveal differential cDNA expression in blood cells between AS and mCRPC cohorts, but not between progressive and non-progressive patients. Therefore, the study design was defective because the obtained differential expression may not reflect what really happened in low risk cancer progression. To our knowledge, there has been no differential genetic expression study or the GSEA study for AS cohort. In addition, we have the largest Taiwanese/Chinese cohort on AS/WW and abundant serial biopsy specimens. In summary, our study which focuses on genomic research on AS cohort is a new strategy to prevent clinical PC and is of high novelty and clinical implications.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Transurethral Prostate Enucleation in Surveillance Protocol for Low Risk Prostate Cancer	NCT05631080	Prostate Cancer... Bladder Outlet ...	Anatomical Endo...	18 Years -	Mansoura University
Targeted Microwave Focal Therapy	NCT04627896	Prostate Cancer...	Katty focal the...	45 Years - 80 Years	Azienda Ospedaliera Città della Salute e della Scienza di Torino
Targeted Microwave Focal Therapy	NCT04627896	Prostate Cancer...	Katty focal the...	45 Years - 80 Years	Azienda Ospedaliera Città della Salute e della Scienza di Torino
Identify Genes/Pathways Responsible for Progression From Low Risk to Higher Risk Prostate Cancer	NCT03789253	Prostate Cancer...		40 Years - 100 Years	National Taiwan University Hospital
Transurethral Prostate Enucleation in Surveillance Protocol for Low Risk Prostate Cancer	NCT05631080	Prostate Cancer... Bladder Outlet ...	Anatomical Endo...	18 Years -	Mansoura University

Spots Global Cancer Trial Database for prostate cancer stage i