Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug Administration, American Urological Association, and Society of Urologic Oncology Public Workshop

doi:10.1016/j.urology.2015.11.018

Urology

Volume 88, February 2016, Pages 8-13

https://doi.org/10.1016/j.urology.2015.11.018 Get rights and content

Objective

To summarize the discussion that took place at a public workshop, co-sponsored by the U.S. Food and Drug Administration, the American Urological Association, and Society of Urologic Oncology reviewing the current state of the art for partial gland ablation (PGA) for the management of patients with prostate cancer. The purpose of this workshop was to discuss potential indications, current available evidence, and designs for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA.

Methods

A workshop evaluating PGA for prostate cancer was held in New Orleans, Louisiana, in May 2015. Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products, technology available, potential indications, and designs of trials to evaluate this modality of therapy.

Results

The panel presented the current information on the technologies available to perform PGA, the potential indications, and results of prior consensus conferences. Use of magnetic resonance imaging for patient selection, guide therapy, and follow-up was discussed. Designs of trials to assess PGA outcomes were discussed.

Conclusion

The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy, but that criteria for patient selection remain debatable, and long-term cancer control remains to be established in properly designed and well-performed prospective clinical trials. Concerns include the potential for excessive, unnecessary use in patients with low-risk cancer and, conversely, that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers, leading to inadequate treatment.

Section snippets

Technology and Potential Indications

Technologies used for the ablation of prostate tissue can be broadly classified into thermal, nonthermal, mechanical, or chemical/toxin-based. Thermal-based technologies include HIFU, cryotherapy, laser thermoablation, radiofrequency ablation, and water vapor or magnetic particle thermotherapy systems. HIFU and cryotherapy are further advanced in clinical development than other modalities with devices on the market in America and Europe.6, 7 Nonthermal systems include irreversible

Imaging

There was general consensus that high-quality imaging is critical for patient selection, treatment guidance, and monitoring. The majority of the panel agreed that (mpMRI) provides the best map of the location and extent of prostate cancers, although MRI may underestimate the extent of cancer in 10-20%. An mpMRI examination consists of a T1-weighted MRI, a T2-weighted MRI, a diffusion-weighted MRI (DW-MRI), and dynamic contrast-enhanced MRI (DCE-MRI). The T1-weighted MRI is used to exclude

Clinical Trial Design

A consensus from the workshop was that the safety and short-term efficacy of PGA could be studied but that demonstration of long-term clinical benefit was not feasible. There was consensus that biopsy, and not PSA, was the best short-term efficacy end point for cancer control; however, biopsy results were viewed with caution because of limited sensitivity for detection of all residual cancer, as well as the lack of a consensus definition of “significant” cancer. Biopsy is limited by sampling

Conclusion

In summary, the panelists agreed that the currently available technologies are capable of selective ablation of the prostate gland with reasonable accuracy, but that criteria for the selection of patients appropriate for PGA remain debatable, and long-term clinical benefit remains to be established in adequately performed randomized clinical trials. Using systematic and targeted needle biopsies, early studies indicate a high rate of conversion to negative biopsy results in areas targeted for

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Cited by (29)

Combination of multiparametric magnetic resonance imaging and transperineal template-guided mapping prostate biopsy to determine potential candidates for focal therapy
2023, Prostate International
We assessed the ability of the combination of multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) to determine the eligibility for focal therapy (FT) (hemiablation) in men and compared it with that of histology from radical prostatectomy (RP) specimens.
In this study, 120 men who underwent mpMRI, TTMB, and RP in a single tertiary center from May 2017 to June 2021 were analyzed. The criteria of hemiablation eligibility were unilateral low-to intermediate-risk prostate cancer (limited to a maximum of International Society of Urological Pathology (ISUP) grade group 3 and prostate-specific antigen (PSA) <20 ng/mL) and clinical stage ≤T2. Evidence of non-organ-confined disease or contralateral Prostate Imaging Reporting and Data System (PI-RADS) v2 score ≥4 on mpMRI was classified as ineligible for hemiablation. Clinically significant cancer at RP was defined as any of the following: (1) ISUP grade group 1 with tumor volume ≥1.3 mL; (2) ISUP grade group ≥2; or (3) the presence of advanced stage (≥pT3).
Of the 120 men, data of 52 men who met the selection criteria for hemiablation were compared with final RP findings. Of these 52 men, 42 (80.7%) could be considered suitable for hemiablation on RP. The sensitivity, specificity, and accuracy of mpMRI and TTMB in predicting FT eligibility were 80.7%, 85.1%, and 82.5%, respectively. The rate of undetected contralateral significant cancer was 10 (19.2%) on mpMRI and TTMB. Six had bilateral significant cancer and four had small volumes of ISUP grade group ≥2.
The combination of mpMRI and TTMB substantially improves the prediction of potential candidates for hemiablation based on consensus recommendations. Improved selection criteria and further investigative tools are required to improve patient selection for hemiablation.
Partial Gland Ablation of Prostate Cancer: Effects of Repeat Treatment
2022, Urology
Citation Excerpt :
Of the 30 men included in the study, 26 had a 6-month biopsy after repeat PGA, and 4 are pending; 29/30 completed quality-of-life symptom questionnaires before and after each treatment. Eligibility criteria for this study were based on consensus recommendations,13 which have been confirmed and adopted at our institution.12 Primary PGA was offered to men with unilateral csPCa of GG1-3 in association with an MRI lesion (PI-RADS>2), with the following provisos: prostate volume <70 cc; no contralateral extension; PSA<20 ng/ml; life expectancy >5 years.
To evaluate the near-term clinical and pathological effects of repeat partial gland ablation (PGA) in men with intermediate-risk prostate cancer (PCa).
One hundred seventy men with focal lesions of PCa (all GG2 or GG3) underwent PGA with high-intensity focused ultrasound (HIFU) or cryotherapy (CRYO) in prospective trials. Residual PCa in or near the ablation zone was found in 37 men after a first PGA; 30 went on to receive a second PGA and were the subjects of study. At 3 timepoints, baseline and 6 months after first and second ablations, quality-of-life (QOL) questionnaires (IIEF, IPSS) and MRI-guided biopsies (MRGB) were performed. Biopsies were targeted and systematic at baseline and in follow-up, comprehensively about the ablation zone.
All 30 patients completed QOL questionnaires and 26 had MRGB at the 3 timepoints. Mean QOL scores were not significantly different from the baseline after the first or second PGA. No operative complications were encountered; and “decisional regret” was reported in only 2/29 men after the repeat ablation. A decrease in semen volume was reported by 25% of patients. Repeat ablation was successful (absence of csPCa on MRGB) in 14/26 (53%) of men. PSA levels decreased and MRI lesions resolved after ablations, but neither was a reliable predictor of biopsy outcomes.
When initial PGA fails, repeat PGA is a reasonable consideration, because in near-term follow-up, secondary procedures appear to be safe, causing only minimal detriment to urinary and sexual function, with csPCa becoming undetectable by MRGB in approximately half the patients.
Potential Candidates for Focal Therapy in Prostate Cancer in the Era of Magnetic Resonance Imaging–targeted Biopsy: A Large Multicenter Cohort Study
2021, European Urology Focus
Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy.
To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources.
Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included.
Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones.
In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15 ng/mL, and life expectancy >10 yr), 303 patients (12.8%; ISUP 1: n = 148 [6.2%]; ISUP 2: n = 155 [6.5%]) were potential candidates for FT. A maximum PSA level of <10 ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n = 288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]).
With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment.
We analyzed how many men who receive a magnetic resonance imaging–targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.
Defining the index lesion for potential salvage partial or hemi-gland ablation after radiation therapy for localized prostate cancer
2021, Urologic Oncology: Seminars and Original Investigations
Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown.
To evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens.
Men who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis.
Primary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides.
Of 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%–89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men.
In men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.
Cribriform pattern and perineural invasion on MR/US fusion biopsy predict failure of selection criteria for prostatic hemigland ablation
2020, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
Furthermore, many of these modalities have been studied in patients with low-risk CaP who could potentially have durable oncologic outcomes with surveillance alone [3]. A key impediment to the greater adoption of focal therapy has been a lack of universally accepted selection criteria despite the work of numerous committees and working groups [1,2]. MR/US fusion biopsy (FB), which includes targeted biopsy (TB) and systematic biopsy (SB) is believed to be an accurate method for selecting patients for definitive primary treatment of CaP [4].
To assess clinicopathologic factors on MR/US fusion biopsy that might predict failure of theoretical selection criteria for prostatic hemigland ablation (HA).
A retrospectively maintained single institution multiparametric MRI database (n = 1667) was queried to identify 355 patients who underwent MR/US fusion biopsy, including both targeted biopsy and concurrent systematic biopsy from December 1, 2014 to June 1, 2018. Clinical, pathological, and imaging variables were assessed on fusion biopsy (Table 1) to determine who met theoretical selection criteria for HA, defined as unilateral intermediate-risk prostate cancer per NCCN criteria (Grade Group [GG] 2 or 3 with prostate-specific antigen <20) and no evidence of extraprostatic extension (EPE) on multiparametric MRI. Predictors of selection criteria failure were then assessed in patients who also underwent radical prostatectomy (RP). Failure of the theoretical HA selection criteria was defined as presence of GG ≧ 2 on the contralateral (untreated) side, or the presence of high-risk disease (any GG ≧ 4 or EPE) in the RP specimen.
Of the 355 patients who underwent fusion biopsy, 84 patients met the theoretical selection criteria for HA. Of those patients eligible, 54 underwent RP, 37 (68.5%) of which represented unsuccessful HA selection criteria. Patients no longer met HA selection criteria on the basis of upgrading alone in 6/54 (11.1%), EPE alone in 9/54 (16.7%), bilateral GG 2 or 3 in 16/54 (29.6%) or combined EPE and bilateral GG 2 or 3 in 6/54 (11.1%) cases. In the HA selection failures due to upgrading, three also had EPE, one of whom also had missed contralateral GG ≧ 2 disease. The only factor independently associated with HA failure was any presence of cribriform pattern (HR 7.01, P = 0.021). Perineural invasion on systematic biopsyalso appeared to improve the performance of our multivariable model (HR 5.33, P = 0.052), though it was not statistically significant when using a cutoff of <0.05. Accuracy for predicting successful HA was 0.32 and improved to 0.74 if PNI or cribriform were excluded and 0.84 if both were excluded.
In a retrospective analysis of RP patients who underwent preoperative MRI/US fusion biopsy, current selection criteria for prostatic HA based on NCCN intermediate-risk stratification failed to accurately identify appropriate candidates in 68.5% of patients. Cribriform pattern and PNI detected on biopsy reduced the failure of hemigland selection criteria to 43%. These criteria should be routinely reported on biopsy pathology and taken into consideration when selecting patients for HA in prospective clinical trials.
Use of MRI-Guided Biopsy for Selection and Follow-up of Men Undergoing Hemi-gland Cryoablation of Prostate Cancer
2019, Urology
To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy.
Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life.
Cryotherapy was completed satisfactorily in all 29 cases in <60 minutes with no intraoperative complications. Significant decreases in PSA (median decrease 5.6 ng/mL) and PSA density (median decrease 0.14 ng/mL/cc) were observed (P < .01). At 6 months, 23 patients (79%) demonstrated no residual cancer on follow-up MRI-guided biopsy of the treated side. Three patients (10%) revealed micro-residual disease. Three patients (10%) had residual cancer and underwent further treatment. Ipsilateral MRI lesions were present before treatment in 26 patients and after treatment in only 2, reflecting the gross ablative effect; however, MRI showed disappearance of lesions in 4 patients with residual tumor on biopsy. The single complication was 1 case of transient urinary retention; 85% of men who were sexually active continued without change after treatment. Voiding function was unchanged.
Hemi-gland cryoablation for clinically-significant CaP is well-tolerated, and when patients are selected and followed by MRI/US fusion biopsy, cancer control appears promising at 6 months.

View all citing articles on Scopus

: Financial Disclosure: Hashim U. Ahmed received clinical trial funding from Sonacare Inc., and also funding for conference travel and honoraria for lectures at courses organized by the said company. He is currently a paid proctor for HIFU. He also received current clinical trial funding from Trod Medical and Sophiris Biocorp. He is previous Consultant for protocol writing at Steba Biotech and is current Consultant for protocol writing for Exact Imaging. He previously received resources from Angiodynamics Inc. through free device and probe use within investigator-led clinical trial. At present, he received resources from Hitachi through free probe use within investigator led clinical trial. Samir S. Taneja is a paid consultant to Hitachi-Aloka and a study investigator for Steba-Biotech and Trod Medical. He received funding from Biobot and Hitachi-Aloka. The remaining authors declare that they have no relevant financial interests.

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Special ReportPartial Gland Ablation for Prostate Cancer: Report of a Food and Drug Administration, American Urological Association, and Society of Urologic Oncology Public Workshop

Objective

Methods

Results

Conclusion

Section snippets

Technology and Potential Indications

Imaging

Clinical Trial Design

Conclusion

Urol Oncol

Eur Urol

Lancet Oncol

Contemp Clin Trials

Eur Urol

Eur Urol

J Urol

Classification of products as drugs and devices and additional product classification issues

Gastroenterology and urology devices panel of the medical devices advisory committee meeting announcement

Gastroenterology and urology devices panel of the medical devices advisory committee meeting announcement

De Novo classification process (Evaluation of Automatic Class III Designation)—Draft guidance for industry and food and drug administration staff

Focal cryotherapy for localized prostate cancer: a report from the national Cryo On-Line Database (COLD) Registry

BJU Int

Focal therapy for localized prostate cancer: a phase I/II trial

J Urol

Special Report
Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug Administration, American Urological Association, and Society of Urologic Oncology Public Workshop