Focal therapy in localised prostate cancer: Real-world urological perspective explored in a cross-sectional European survey

doi:10.1016/j.urolonc.2018.08.013

Urologic Oncology: Seminars and Original Investigations

Volume 36, Issue 12, December 2018, Pages 529.e11-529.e22

https://doi.org/10.1016/j.urolonc.2018.08.013 Get rights and content

Highlights

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The urological community's opinion over focal therapy has never been assessed.
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A survey was devised using EAU and others mailing lists receiving 484 replies.
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A significant proportion deemed FT a step forward and would suggest it to patients.
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70.8% agreed FT will be a standard if improving patients selection and/or confirming FT effectiveness.
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FT is considered as an attractive option by the urologists sampled by our survey.

Abstract

Introduction

The urological community's opinion over focal therapy (FT) for prostate cancer (PCa) has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community.

Methods

A 25-item questionnaire was devised according to the Cherries checklist and distributed through SurveyMonkey using a web link from November 2016 to October 2017. After a pilot validation (n = 40 urologists), the survey was sent through EAU and 9 other national European urological societies mailing list. Twitter was also used.

Results

We received 484 replies from 51 countries. Almost half (44.8%, n = 217) stated FT would represent a step forward, and 52.0% (n = 252) would suggest FT to a patient. Almost three-quarters (70.8%, n = 343) agreed FT will become a standard option after improvements in patient selection (n = 66) or when its effectiveness will be proven (n = 78), or both (n = 199). Most frequently used definition of FT was treatment of all significant (life-threatening) cancer foci whilst leaving untreated the rest of the gland (39.3%, n = 190). FT use was considered as an alternative to whole-gland treatments by 29.7% (n = 144), and to AS by 25.0% (n = 121). On multivariate analysis, FT availability and publications were associated with a positive opinion on FT. Conversely, attending International congresses, treating high PCa volumes and high percentages of high-risk PCa was associated with a negative opinion.

Conclusions

FT is considered as an attractive option for PCa treatment by the European urological community sampled by our survey. FT availability positively influences these thoughts. The present survey suggests whilst some early adopters already embraced FT, the relative majority of the urological community is prone to embrace FT in the near future, once current areas of debate are solved.

Introduction

Modern surgical oncology is increasingly moving towards tissue-preserving strategies over radical approaches in the vast majority of malignancies, provided that such approaches are technically feasible and oncologically effective [1], [2], [3], [4]. Whilst there is some interest in such a concept for prostate cancer (PCa), the prostate does still remain the last solid organ for which whole-gland treatments are carried out as standard of care. It is indeed an exception to treat in the same manner men harbouring measurable disease ranging from high volume low-risk to high-risk disease. Further, the risk ratio of whole-gland treatments provides low therapeutic effectiveness in men with disease, as the little long-term survival benefit is outweighed by the significant treatment-related genitourinary and rectal toxicity [5], [6].

In this milieu, focal therapy (FT) for PCa has emerged to maintain oncological benefit of immediate treatment whilst significantly decreasing treatment-related toxicity [6]. There remains controversy over this strategy and learned societies range from conservative statements recommending FT only within clinical trials—for instance, the EAU guidelines [5], [7]—to recommending centres to adopt FT, as long as quality control and local governance can be ensured—for instance, the NICE Interventional guidelines [8]. Areas of debate include (i) PCa biology and pathology with the key issue of multifocality; (ii) patient selection with potential for diagnostic inaccuracy; (iii) lack of standardisation of treatment with heterogeneity of energy source, treatment delivery, and follow-up modalities; and (iv) lack of explanatory level 1 evidence in the medium long term [9], [10], [11], [12], [13].

These unsolved issues generate vibrant debates amongst pioneers and early adopters on one side, and opponents of FT adoption on the other [9], [10], [11], [12], [13]. Nonetheless, the discussion concerning FT use remains mainly restricted to a few academic groups, whilst the urological community's overall perception of FT has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community through a broad cross-sectional survey.

Section snippets

Materials and Methods

A 25-item-anonymised English language open questionnaire including 12 questions on baseline demographics, 9 on FT, and 4 clinical cases (Supplementary Material 1) was devised by the European Association of Urology Young Academic Urologists PCa working group. The Checklist for Reporting Results for E-Survey (CHERRIES checklist) was used [14]. Participants answered the Survey on a volunteer basis and no incentives were proposed. The items were not randomised; respondents were free to change their

Results

In total, 484 replies were received, 417 (86.16%) of which were completed. The remaining answers from incomplete questionnaires (13.84%) were included in the cumulative analysis. We did not measure the response rate, as the number of members per society and double receivers were not available. However, with the sole EAU mailing list, more than 38,000 practitioners received the survey, which means that the response rate was low.

Respondents’ baseline features are displayed in Table 2. Over 90% of

Discussion

To our knowledge, this is the first international survey aiming to investigate the opinion and perceptions of the European urological community on the current and future role of FT in PCa. We believe there are 3 key findings in our study.

First, there is high awareness regarding FT, and more importantly this novel strategy seems available to many. Less than 1 in 20 physicians had never heard about FT; less than 1 in 3 reported this was not available as a treatment option either in their own

Conclusions

FT is considered as an attractive option for PCa treatment by the urological community sampled in our questionnaire, with the relative but not an absolute majority of responders stating they would recommend it to suitable patients, it may become a standard option upon improvement of patient selection and/or demonstration of its effectiveness, and it would represent a step forward in PCa treatment. Significant selection bias inherent to the type of respondents and the methodology employed may

Conflicts of Interest

HUA receives funding from Sonacare Inc, Sophiris Bio, Trod Medical, and Galil/BTG Ltd for focal therapy research. He is a paid consultant to Sophiris Bio for trial work. He is a paid proctor for HIFU (Sonacare) and cryotherapy (Galil/BTG Ltd). HUA carries out FT in his clinical practice. All other authors have no potential conflicts of interest to declare.

Acknowledgements

HUA would like to acknowledge core support from the National Institute of Health Research (UK) Imperial Biomedical Research Centre. The authors would like to acknowledge the following collaborators:

Roberto Carone—SIU—Società Italiana di Urologia former president and Department of Urology, CTO Hospital, Città della Salute e della Scienza and University of Turin, Turin, Italy.

Francesco Sanguedolce—Department of Urology, Fundacio Puigvert, Barcelona, Spain.

Arnaldo Figueiredo—APU—Associacao

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Cited by (32)

Partial-gland Cryoablation Outcomes for Localized Prostate Cancer in Patients with Magnetic Resonance Imaging (MRI)-visible and MRI-invisible Lesions
2023, European Urology Open Science
Expert consensus recommends treatment of magnetic resonance imaging (MRI)-visible prostate cancer (PCa). Outcomes of partial-gland ablation (PGA) for MRI-invisible PCa remain unknown.
To compare recurrence-free survival, adverse events, and health-related quality of life (HRQoL) outcomes following cryoablation of MRI-visible vs invisible PCa.
We analyzed data for 75 men who underwent cryoablation therapy between January 2017 and January 2022. PCa identified on MRI-targeted and/or adjacent systematic biopsy cores was defined as MRI-visible, whereas PCa identified on systematic biopsy beyond the targeted zone was defined as MRI-invisible.
The primary outcome was recurrence at 12 mo after PGA, defined as the presence of clinically significant PCa (grade group [GG] ≥2) on surveillance biopsy. Adverse events were captured using the Clavien-Dindo classification and HRQoL was captured using the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP) tool.
Of the 58 men treated for MRI-visible and 17 treated for MRI-invisible lesions, 51 (88%) and 16 (94%), respectively, had at least one surveillance biopsy performed. There were no statistically significant differences in age, race, body mass index, biopsy GG, prostate-specific antigen, prostate volume, or treatment extent between the MRI-visible and MRI-invisible groups. Median follow-up was 44 mo (interquartile range 17–54) and did not significantly differ between the groups. The recurrence rate at 12 mo did not significantly differ between the groups (MRI-visible 39%, MRI-invisible 19%; p = 0.2), and log-rank survival analysis demonstrated no significant difference in recurrence-free survival (p = 0.15). Adverse event rates did not significantly differ (MRI-visible 29%, MRI-invisible 53%; p = 0.092); no man in the MRI-visible group had a Clavien-Dindo grade ≥III complication, while one subject in the MRI-invisible group had a Clavien-Dindo grade III complication. Median EPIC-CP urinary and sexual function scores were similar for the two groups at baseline and at 12 mo after PGA. Study limitations include the retrospective design and small sample size.
We observed similar cancer control, adverse event, and HRQoL outcomes for MRI-visible versus MRI-invisible PCa in the first comparison of partial-gland cryoablation. Longer follow-up and external validation of our findings are needed to inform patient selection for PGA for MRI-invisible PCa.
Patients with prostate cancer lesions that are not visible on magnetic resonance imaging (MRI) scans who undergo partial gland ablation may have similar treatment outcomes compared to patients with cancer lesions that are visible on MRI.
The Association of Tissue Change and Treatment Success During High-intensity Focused Ultrasound Focal Therapy for Prostate Cancer
2023, European Urology Focus
Citation Excerpt :
Of note, the utility of PI-RADS scoring and MRI interpretation after focal ablation for the detection of residual cancer is debated due to the small size of residual lesions, presence of nonspecific cavities, and postablation changes that are difficult to differentiate from cancer even on dynamic contrast enhanced MRI [8,15,16]. Yet, PI-RADS scoring of mpMRI continues to be utilized both in clinical trials and for routine postablation management to guide the timing of biopsy, thus warranting inclusion in any study evaluating postablation outcomes [2,17]. Third, high TCM measurements were associated with increased tissue destruction seen on MRI 12 mo after ablation.
Tissue preservation strategies have been increasingly used for the management of localized prostate cancer. Focal ablation using ultrasound-guided high-intensity focused ultrasound (HIFU) has demonstrated promising short and medium-term oncological outcomes. Advancements in HIFU therapy such as the introduction of tissue change monitoring (TCM) aim to further improve treatment efficacy.
To evaluate the association between intraoperative TCM during HIFU focal therapy for localized prostate cancer and oncological outcomes 12 mo afterward.
Seventy consecutive men at a single institution with prostate cancer were prospectively enrolled. Men with prior treatment, metastases, or pelvic radiation were excluded to obtain a final cohort of 55 men.
All men underwent HIFU focal therapy followed by magnetic resonance (MR)-fusion biopsy 12 mo later. Tissue change was quantified intraoperatively by measuring the backscatter of ultrasound waves during ablation.
Gleason grade group (GG) ≥2 cancer on postablation biopsy was the primary outcome. Secondary outcomes included GG ≥1 cancer, Prostate Imaging Reporting and Data System (PI-RADS) scores ≥3, and evidence of tissue destruction on post-treatment magnetic resonance imaging (MRI). A Student's t - test analysis was performed to evaluate the mean TCM scores and efficacy of ablation measured by histopathology. Multivariate logistic regression was also performed to identify the odds of residual cancer for each unit increase in the TCM score.
A lower mean TCM score within the region of the tumor (0.70 vs 0.97, p = 0.02) was associated with the presence of persistent GG ≥2 cancer after HIFU treatment. Adjusting for initial prostate-specific antigen, PI-RADS score, Gleason GG, positive cores, and age, each incremental increase of TCM was associated with an 89% reduction in the odds (odds ratio: 0.11, confidence interval: 0.01–0.97) of having residual GG ≥2 cancer on postablation biopsy. Men with higher mean TCM scores (0.99 vs 0.72, p = 0.02) at the time of treatment were less likely to have abnormal MRI (PI-RADS ≥3) at 12 mo postoperatively. Cases with high TCM scores also had greater tissue destruction measured on MRI and fewer visible lesions on postablation MRI.
Tissue change measured using TCM values during focal HIFU of the prostate was associated with histopathology and radiological outcomes 12 mo after the procedure.
In this report, we looked at how well ultrasound changes of the prostate during focal high-intensity focused ultrasound (HIFU) therapy for the treatment of prostate cancer predict patient outcomes. We found that greater tissue change measured by the HIFU device was associated with less residual cancer at 1 yr. This tool should be used to ensure optimal ablation of the cancer and may improve focal therapy outcomes in the future.
The Changing Face of cN0M0 Prostate Cancer Being Found With pN+ After Surgery in the Contemporary Era: Results of an International European Survey on Disease Management
2023, Clinical Genitourinary Cancer
The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community.
Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used.
We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05).
The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered.
Salvage Radical Prostatectomy for Recurrent Prostate Cancer After Primary Nonsurgical Treatment: An Updated Systematic Review
2023, European Urology Focus
Salvage radical prostatectomy (sRP) has historically been associated with high morbidity, whilst recently published multicentre series suggested a trend towards improved outcomes. Hence, we performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria to investigate the oncological and functional results and morbidity of sRP. We included 20 retrospective articles comprising 4175 men. Robotic procedures were performed in 40% and nerve sparing in up to 36% of men. Postoperative continence was preserved in 40.4% of patients and erectile function in <16%. High-grade complications were described in 6.6% of patients (rectal injuries 0.9%). At final sRP pathology, surgical margins were positive in 26.1%, 32.8% had seminal vesicle invasion, and International Society of Urological Pathology grade was >3 in 26.6%. Ten-year metastasis-free survival ranged from 72% to 77% and 5-yr cancer-specific survival ranged from 86.6% to 97.7%. Salvage radical prostatectomy shows durable oncological control and morbidity improved over recent years, despite remaining significant compared to and higher than that of primary radical prostatectomy.
Salvage radical prostatectomy (sRP) shows improving oncological control and morbidity over time. The complications associated with sRP and its functional results seem to be acceptable and are continuously improving.
Recurrent Gleason Score 6 Prostate Cancer After Radiotherapy or Ablation: Should We Observe Them All? Results from a Large Multicenter Salvage Radical Prostatectomy Consortium
2023, European Urology Focus
Salvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated.
To evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa.
Retrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021.
Prostate biopsy before sRP and sRP.
A survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed.
We included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61–89%), 98% (95–99%), and 89% (78–95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58–98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review.
GS 6 sRP–proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy.
We investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease.
Focal High-Intensity Focused Ultrasound vs. Active Surveillance for ISUP Grade 1 Prostate Cancer: Medium-Term Results of a Matched-Pair Comparison
2022, Clinical Genitourinary Cancer
Citation Excerpt :
Focal therapy (FT) for localized prostate cancer (PCa) aims to reduce side effects from the radical whole-gland treatments while maintaining the oncologic benefits of those treatments.1,2 FT is gaining ground among PCa clinicians and patients,3-5 and the number of treated men and available studies are growing rapidly.2 Nonetheless, the current guideline panels do not recognize FT as a standard option and recommend that its use be limited to clinical trials and prospective registries.6
Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa.
We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS).
Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949).
At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

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Original articleFocal therapy in localised prostate cancer: Real-world urological perspective explored in a cross-sectional European survey

Highlights

Abstract

Introduction

Methods

Results

Conclusions

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusions

Conflicts of Interest

Acknowledgements

Eur Urol

Eur Urol

Eur Urol

Eur Urol

Eur Urol

Eur Urol

Lancet Oncol

J Urol

Eur Urol

Penile sparing surgery for penile cancer: a multicenter international retrospective cohort

J Urol

Treatment of early-stage breast cancer

JAMA

Minimally invasive resection of early lung cancers

Oncology

Original article
Focal therapy in localised prostate cancer: Real-world urological perspective explored in a cross-sectional European survey