Tag Archive for: focal therapy

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Editorial: Doubling our precision of risk stratification in early prostate cancer? Too good to be true?

It is difficult to over-estimate the enormity of the revolution involved in transitioning away from an organ-based system of care in prostate cancer (prostatectomy or radiotherapy to prostate cancer of any grade, number, location or volume) to one in which the target condition is defined and verified, and then subsequently treated with a margin. Since Hugh Hampton-Young undertook the first radical prostatectomy more than 100 years ago, an organ-based system of care has been the only plausible strategy for men with early-stage prostate cancer. This is because our risk stratification methods could certainly tell us who had prostate cancer when it was indeed identified, but they could not tell us with any degree of precision how much cancer was present (number of foci and volume of cancer), what grade it was and where within the prostate the cancer resided. Surgery or radiotherapy to the whole gland, it was thought, was a reasonable mitigation (at the cost of over-treatment in a significant proportion of men) to the systematic under-estimation of risk to the patient. The degree to which our attempts at risk stratification failed our patients was emphasized in a recent UK report that showed an increase of >50% in histological grade (the most important determinant of risk) at radical prostatectomy compared with the risk the patient was told at the time of diagnosis[1]. ‘Upgrading’ is an inverse measure of the quality of our risk stratification.

With this background it should be of little surprise that there remains considerable skepticism about our ability to localize disease within the prostate, define its volume with some degree of precision and identify the worst histological grade within the tumour most of the time. These conditions, which most patients, quite reasonably, might expect of a modern cancer diagnostic programme, need to be fulfilled if we are to move away from an organ-based strategy for all towards a system of care that risk stratifies with precision, treats only those who are likely to benefit and tries to preserve tissue and function when we are able to do so.

The technologies and developments that have permitted a reduction in risk stratification error from 50 to ~5% are the subject of a paper by Tran et al. [2] in the present issue of BJUI. This group from Australia exploited a cohort of men that underwent a series of tests that culminated in a radical prostatectomy. These comprised: high-quality multiparametric MRI at a range of magnet strengths; formal scoring of the MRI using an ordinal scale of risk; a subsequent 5-mm transperineal template-guided biopsy modified from Winston Barzell’s original account; and additional sampling of prostate sectors that corresponded to a high likelihood of clinically significant cancer based on the MRI reading, a process otherwise known as ‘targeting’. The outputs of these tests were compared with the presence or absence of clinically significant prostate cancer in the 100 prostate lobes evaluated from the 50 eligible men who underwent surgery. The authors’ a priori threshold for declaring clinically significant disease in the tests was the presence or a PIRADS 4–5 MRI lesion (with or without concordant pathology) and/or the presence of exclusive Gleason pattern 3 amounting to ≥4 mm maximum cancer core length or the presence of any Gleason pattern 4 or 5 [3]. At radical prostatectomy slightly different criteria were employed. Clinically significant prostate cancer constituted an exclusive Gleason pattern 3 lesion provided it was ≥1.3 mL. The presence of patterns 4 and 5 within the lesion triggered ‘significance’, as did evidence of capsular invasion or extraprostatic extension.

Although it was a small study, the men included were exposed to the best diagnostic profile that it was possible to have and were subjected to a reference test which most of us would trust. What did they find? Just how well did a modern diagnostic panel rule in or rule out prostate cancer that exceeded a minimum threshold of 4 mm of Gleason pattern 3? Within the hundred lobes that were evaluated, 21 clinically significant cancers were identified in the diagnostic process. At radical prostatectomy two of these were at the midline and therefore attributed, within the rules, to both sides of the gland. In one of these cases there was a 5-mm diameter (0.1 mL) Gleason 3+4 lesion with 10% Gleason pattern 4 that was overlooked by the combined diagnostic process. A lesion of this volume can evade a well-applied sampling strategy based on a 5-mm sampling frame, especially if the lesion is non-spherical. The relatively low component of pattern 4 combined with the relatively low volume means that MRI would also have a hard time detecting it. Under the conditions described in the present paper, the authors concluded that combined MRI and intensive biopsy conferred a sensitivity of 97% and a negative predictive value of 91% for a fairly conservative definition of clinically significant disease. This level of accuracy, which is nearly twice as good as that of which we were previously capable, will result in major benefits for patients in terms of communicating risk with an order of precision that was hitherto not possible. This should translate to more appropriate treatment allocation, both avoiding unnecessary treatment and having treatment when it is likely to be beneficial. It should also result in a significant proportion of patients being offered the option of a tissue-preserving therapy when this is an option [4]. Most importantly, this new precision opens up an opportunity for greater involvement of the patient in the process of informed decision-making [5]. Something that was not really possible in the face of yesterday’s diagnostic uncertainty.

Mark Emberton
Division of Surgery and Interventional Science, University College London, London, UK

 

References

 

Video: Combination of mpMRI and TTMB of the prostate to identify candidates for hemi-ablative FT

Combination of multi-parametric magnetic resonance imaging (mp-MRI) and transperineal template-guided mapping biopsy (TTMB) of the prostate to identify candidates for hemi-ablative focal therapy

Minh Tran*†‡, James Thompson*§, Maret Bohm†, Marley Pulbrook, Daniel Moses¶, Ron Shnier**, Phillip Brenner*§, Warick Delprado††, Anne-Maree Haynes†, Richard Savdie§ and Phillip D. Stricker*§

 

*St Vincents Prostate Cancer CentreGarvan Institute of Medical Research & The Kinghorn Cancer Centre, DarlinghurstSchool of Medicine, University of Sydney§School of Medicine, University of New South Wales, SydneySpectrum Medical Imaging , **Southern Radiology, Randwick, and†† Douglass Hanly Moir Pathology, Darlinghurst, NSW, Australia

 

OBJECTIVE

To evaluate the accuracy of combined multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) for identifying lobes with significant prostate cancer (PCa) for the application of hemi-ablative focal therapy (FT).

PATIENTS AND METHODS

From January 2012 to January 2014, 89 consecutive patients, aged ≥40 years, with a PSA level ≤15 ng/mL, underwent in sequential order: mpMRI, TTMB and radical prostatectomy (RP) at a single centre. Analysis was performed on 50 patients who met consensus guidelines for FT. Lobes were stratified into lobes with significant cancer (LSC), lobes with insignificant cancer and lobes with no cancer. Using histopathology at RP, the predictive performance of combined mpMRI + TTMB in identifying LSC was evaluated.

RESULTS

The sensitivity, specificity and positive predictive value for mpMRI + TTMB for LSC were 97, 61 and 83%, respectively. The negative predictive value (NPV), the primary variable of interest, for mpMRI + TTMB for LSC was 91%. Of the 50 patients, 21 had significant unilateral disease on mpMRI + TTMB. Two of these 21 patients had significant bilateral disease on RP not identified on mpMRI + TTMB.

CONCLUSIONS

In the selection of candidates for FT, a combination of mpMRI and TTMB provides a high NPV in the detection of LSC.

Read more articles of the week

Step-by-Step. Real time TRUS-guided free-hands technique for focal cryoablation of the prostate

 

 

 

 

Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate

Andre Luis de Castro Abreu, Duke Bahn*, Sameer Chopra, Scott Leslie, Toru Matsugasumi, Inderbir S. Gill and Osamu Ukimura

USC Institute of Urology, Catherine and Joseph Aresty Department of Urology, Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and *Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

How to Cite: de Castro Abreu, A. L., Bahn, D., Chopra, S., Leslie, S., Matsugasumi, T., Gill, I. S. and Ukimura, O. (2014), Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate. BJU International, 114: 784–789. doi: 10.1111/bju.12795

Read the full article

Objectives

To describe, step-by-step, our hands-free technique for focal cryoablation of prostate cancer.

Materials and Methods

After detailed discussion of its limitations and benefits, consent was obtained to perform focal cryoablation in patients with biopsy-proven unilateral low- to intermediate-risk prostate cancer. The procedure was performed transperineally, using a hands-free technique (without an external grid template) under real-time bi-plane transrectal ultrasonography (TRUS) guidance, using an argon/helium-gas-based third generation cryoablation system. Follow-up consisted of validated questionnaires, physical examination, PSA measures, multiparametric TRUS and/or magnetic resonance imaging (MRI) and mandatory biopsy.

Results

The important steps for achieving safety, satisfactory oncological and functional outcomes included: patient selection, including TRUS/MRI fusion target biopsy; thermocouple and cryoprobe placement with a hands-free technique, allowing delivery in unrestricted angulations according to the prostatic contour, the course of the neurovascular bundle and the rectal wall angle; and hands-free bi-plane TRUS probe manipulation to facilitate real-time monitoring of anatomical landmarks at the ideal angle of the image plane. To achieve a lethal temperature in the known cancer area, while preserving the urinary sphincter, neurovascular bundle, urethra and rectal wall, continuous intraoperative control of the thermocouple temperatures was necessary, as were real-time TRUS monitoring of ice-ball size, control of the energy delivered and the use of a warming urethral catheter.

Conclusion

We have described step-by-step the focal cryoablation of prostate cancer using a hands-free technique. This technique facilitates the effective delivery of cryoprobes and the intra-operative real-time quick manipulation of the TRUS probe.

 

A novel deformable MR-US registration system

Image-directed, tissue-preserving focal therapy of prostate cancer: a feasibility study of a novel deformable magnetic resonance-ultrasound (MR-US) registration system

Louise Dickinson*, Yipeng Hu, Hashim U. Ahmed*, Clare Allen§, Alex P. Kirkham§, Mark Emberton* and Dean Barratt

Departments of *Urology and §Radiology, University College London Hospitals NHS Foundation Trust, Division of Surgery and Interventional Sciences and Centre for Medical Image Computing and Department of Medical Physics and Bioengineering, Univeristy College London, London, UK

Read the full article
OBJECTIVE

• To evaluate the feasibility of using computer-assisted, deformable image registration software to enable three-dimensional (3D), multi-parametric (mp) magnetic resonance imaging (MRI)-derived information on tumour location and extent, to inform the planning and conduct of focal high-intensity focused ultrasound (HIFU) therapy.

PATIENTS AND METHODS

• A nested pilot study of 26 consecutive men with a visible discrete focus on mpMRI, correlating with positive histology on transperineal template mapping biopsy, who underwent focal HIFU (Sonablate 500®) within a prospective, Ethics Committee-approved multicentre trial (‘INDEX’).

• Non-rigid image registration software developed in our institution was used to transfer data on the location and limits of the index lesion as defined by mpMRI.

• Manual contouring of the prostate capsule and histologically confirmed MR-visible lesion was performed preoperatively by a urologist and uro-radiologist.

• A deformable patient-specific computer model, which captures the location of the target lesion, was automatically generated for each patient and registered to a 3D transrectal ultrasonography (US) volume using a small number (10–20) of manually defined capsule points.

• During the focal HIFU, the urologist could add additional sonications after image-registration if it was felt that the original treatment plan did not cover the lesion sufficiently with a margin.

RESULTS

• Prostate capsule and lesion contouring was achieved in <5 min preoperatively. The mean (range) time taken to register images was 6 (3–16) min.

• Additional treatment sonications were added in 13 of 26 cases leading to a mean (range) additional treatment time of 45 (9–90) s.

CONCLUSION

• Non-rigid MR-US registration is feasible, efficient and can locate lesions on US.

• The process has potential for improved accuracy of focal treatments, and improved diagnostic sampling strategies for prostate cancer.

• Further work on whether deformable MR-US registration impacts on efficacy is required.

Article of the week: Salvage focal or total cryoablation after failed primary radiotherapy: which is better?

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

This week, we feature two Articles of the Week.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

The final post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video by Dr. de Castro Abreu and colleagues.

Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy

Andre Luis de Castro Abreu*, Duke Bahn*, Scott Leslie*, Sunao Shoji*, Paul Silverman, Mihir M. Desai*, Inderbir S. Gill* and Osamu Ukimura*

*USC Institute of Urology, Hillard and Roclyn Herzog Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

Read the full article
OBJECTIVES

• To present the oncological and functional outcomes of salvage focal (SFC) and salvage total (STC) cryoablation for recurrent prostate cancer (PCa) after failed primary radiotherapy.

PATIENTS AND METHODS

• From March 2003 to August 2010, 50 men with biopsy-proven unilateral (n = 25) or bilateral (n = 25) radio-recurrent PCa underwent SFC or STC, respectively.

• Patients were assessed after treatment by prostate-specific antigen (PSA) testing, transrectal ultrasonography, biopsy and questionnaires. Biochemical failure (BF) was defined using the Phoenix criteria (PSA nadir + 2 mg/mL).

• Data were prospectively collected and retrospectively analysed.

RESULTS

• The median pre-cryoablation PSA level and Gleason score were, respectively, 2.8 ng/mL and 7 for SFC, and 3.9 ng/mL and 7 for STC. The median follow-up was 31 and 53 months (P = 0.004) for SFC and STC, respectively.

• Oncological outcomes were as follows: no patient died; one patient who underwent STC developed bone metastases; eight patients who underwent SFC and three who underwent STC had BF and the 5-year BF-free survival rates were 54 and 86%, respectively. In those patients without BF, the mean PSA decreased by 86% for SFC and 90% for STC within the first year and remained stable.

• Functional outcomes were as follows: new onset urinary incontinence occurred in three (13%) patients in the STC group, whereas no patient in the SFC group developed incontinence (P = 0.10); Two of seven patients in the SFC group retained postoperative potency, but none of the four potent patients in the STC group recovered potency postoperatively (P = 0.48); one (4%) patient in the STC group developed a recto-urethral fistula, but none occurred in the SFC group (P = 0.48).

CONCLUSIONS

• SFC and STC are feasible and safe with acceptable mid-term oncological outcomes. For carefully selected patients, SFC is an option that could be associated with lower treatment-related morbidity compared with STC.

• Although longer follow-up and more patient numbers are needed, our initial oncological and functional outcomes of SFC and STC are encouraging.

 

Read Previous Articles of the Week

 

Editorial: Salvaging failed radiation therapy: does the tumour location permit a less toxic approach?

In the introduction to their manuscript in this issue of the BJUI, Meeks et al. outline a significant challenge for physicians managing prostate cancer: from the estimated 240 000 diagnosed annually (USA) to the 120 000 choosing radiation, to the 40 000 estimated biochemical failures in the first 5 years who may benefit from additional local therapy to avoid local and/or systemic progression. The basis of these calculations was from conventional beam radiation, and although we expect dose-escalation strategies to perform better, the ideal management strategy remains to be identified. Indeed, Zelefsky et al. showed that there was a higher risk of metastatic disease with external beam radiation therapy than with surgery for high-risk prostate cancer, although there was some confounding of the results due to the differences in salvage treatment. This confounding may be the key point: more acceptable salvage options may promote optimal local control and fewer progressions.

Certainly, the concern with salvage therapy after failed radiation is the toxicity, and the concept of achieving less urinary incontinence with cryotherapy or even focal cyrotherapy is attractive, as outlined by de Castro Abreu et al. in this issue. In their parallel cohorts of total and focal salvage cryotherapy, urinary incontinence occurred in three (13%) of the 25 salvage total and zero of the 25 salvage focal therapies, and there was only one fistula in either series. However, the cancer control outcomes are different among these non-randomised and non-comparable cohorts: 87% disease-free survival for patients with bilateral disease treated with total cryotherapy and 54% disease-free survival for patients with unilateral disease treated with focal cryotherapy. These comparisons are limited, but one could hypothesise that salvage total therapy has improved disease control over salvage focal therapy.

Returning to the Meeks et al. study, a cohort of 198 patients with biopsy confirmed radiation recurrence underwent a salvage prostatectomy at a single institution. Pre-treatment biopsies showed 48% and 13% Gleason sums 7 and 8–10, respectively, and multifocal location in 61% (92/151 patients). Salvage prostatectomies showed 56% advanced pathological stage and 35% Gleason 8–10, and multifocal location in 57%. In comparing specific biopsy locations to radical prostatectomy mapping, undetected cancers from biopsy ranged from 12% to 26%, and 58% upgrading. In patients with unilaterally localised biopsies, final pathology was unilateral in only half – a statistic that matches the PSA failure rate from focal therapy in the de Castro Abreu et al.’s study. The authors point to a non-radiated biopsy-to-prostatectomy study and by comparison conclude that the accuracy of biopsy in radiated prostates is actually greater, perhaps due to the smaller radiated gland. But let’s be clear – both groups had significant rates of multifocal disease and inaccuracies between biopsy and radical prostatectomy.

These two BJUI studies provide a developing agenda of what we know and do not know about salvage therapy for failed radiation:

  • Local failure after radiation selects patients who probably have significant disease in terms of volume, stage, and grade, and should not be confused with the over-detection of low-volume, low-grade disease seen in primary treatments for PSA-screened disease.
  • Salvage focal therapy for unilateral disease by biopsy may be less morbid but may be only 50% effective.
  • The link between metastatic progression and PSA failure after failed salvage focal therapy is unknown, and completion treatment of the other side could be studied.
  • The additive accuracy of post-radiation biopsy plus imaging is not established.
  • We are basing most of our treatment recommendations on tumour morphology (histopathology, location, size) and surrogates (PSA failure definitions) rather than biology and survival.
  • The current management of post-radiation local failure should consider total gland treatments as the standard and focal therapies as experimental.

John W. Davis and Seungtaek Choi*
Departments of Urology and *Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, USA

Article by Meeks et al.
Article by de Castro Abreu et al.

Video: Cryoablation after failed primary radiotherapy: study finds encouraging results

Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy

Andre Luis de Castro Abreu*, Duke Bahn*, Scott Leslie*, Sunao Shoji*, Paul Silverman, Mihir M. Desai*, Inderbir S. Gill* and Osamu Ukimura*

*USC Institute of Urology, Hillard and Roclyn Herzog Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

Read the full article
OBJECTIVES

• To present the oncological and functional outcomes of salvage focal (SFC) and salvage total (STC) cryoablation for recurrent prostate cancer (PCa) after failed primary radiotherapy.

PATIENTS AND METHODS

• From March 2003 to August 2010, 50 men with biopsy-proven unilateral (n = 25) or bilateral (n = 25) radio-recurrent PCa underwent SFC or STC, respectively.

• Patients were assessed after treatment by prostate-specific antigen (PSA) testing, transrectal ultrasonography, biopsy and questionnaires. Biochemical failure (BF) was defined using the Phoenix criteria (PSA nadir + 2 mg/mL).

• Data were prospectively collected and retrospectively analysed.

RESULTS

• The median pre-cryoablation PSA level and Gleason score were, respectively, 2.8 ng/mL and 7 for SFC, and 3.9 ng/mL and 7 for STC. The median follow-up was 31 and 53 months (P = 0.004) for SFC and STC, respectively.

• Oncological outcomes were as follows: no patient died; one patient who underwent STC developed bone metastases; eight patients who underwent SFC and three who underwent STC had BF and the 5-year BF-free survival rates were 54 and 86%, respectively. In those patients without BF, the mean PSA decreased by 86% for SFC and 90% for STC within the first year and remained stable.

• Functional outcomes were as follows: new onset urinary incontinence occurred in three (13%) patients in the STC group, whereas no patient in the SFC group developed incontinence (P = 0.10); Two of seven patients in the SFC group retained postoperative potency, but none of the four potent patients in the STC group recovered potency postoperatively (P = 0.48); one (4%) patient in the STC group developed a recto-urethral fistula, but none occurred in the SFC group (P = 0.48).

CONCLUSIONS

• SFC and STC are feasible and safe with acceptable mid-term oncological outcomes. For carefully selected patients, SFC is an option that could be associated with lower treatment-related morbidity compared with STC.

• Although longer follow-up and more patient numbers are needed, our initial oncological and functional outcomes of SFC and STC are encouraging.

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