brachytherapy

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IP4-CHRONOS is launched

December 11, 2019/by Deepika Reddy

IP4- CHRONOS is open! CHRONOS is a phase II randomised control trial, that will review the outcomes (including oncological, functional, quality of life and cost-effectiveness) of focal therapy against those from radical therapy, in men with newly diagnosed localised clinically significant prostate cancer.

All men newly diagnosed with low-intermediate risk prostate cancer, confined to the prostate, with a life expectancy of at least 10 years will be screened for eligibility. Men must be well enough to undergo the interventions outlined in the trial prior to being enrolled.

Men will then have a choice of enrolling into CHRONOS A or CHRONOS B. CHRONOS A will randomise men to having radical whole gland treatment (radiotherapy, brachytherapy or prostatectomy), or focal therapy (HIFU or cryotherapy). CHRONOS A will answer the question, ‘is focal therapy equivalent in cancer control as radical therapy?’ CHRONOS B will randomise men to having focal therapy with or without additional neoadjuvant treatment and will answer the question: ‘can the success of focal therapy be improved by using neoadjuvant treatment?’ Randomisation will be stratified by disease characteristics.

All men will undergo intervention as they would within the NHS, however by doing so in a trial setting, we can directly compare the results of such treatments against each other. As the follow up mimics that of standard of care, the extra burden of treatment within the trial is minimal.

60 men will be recruited into both CHRONOS A and CHRONOS B (total 120) over a 1-year period, during the pilot, and if recruitment is successful the aim is to continue to a larger study assessing 2450 patients over 5 years, with a minimum follow up of 3 years. The primary outcome measures will be progression free survival in CHRONOS A, and failure free survival in CHRONOS B. The CHRONOS pilot will open in 12 UK hospital sites, aiming to open across the UK and Europe within the larger study.

CHRONOS is entirely funded by the Prostate Cancer UK charity, and available on the NIHR CRN portfolio. If you would like to join the main phase of CHRONOS as a site, please contact Miss Deepika Reddy ([email protected]) or visit our website for further information www.imperialprostate.org.uk/CHRONOS

Prof Hashim U. Ahmed (CHRONOS PI&CI)

Mr Taimur T. Shah (CHRONOS sub-investigator, Urology SpR & Research Fellow)

Miss Deepika Reddy (CHRONOS Clinical Research Fellow)

Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer

October 1, 2018/by Admin

Abstract:

Decisions regarding the primary treatment of prostate cancer depend on several patient‐ and disease‐specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of ‘localised’ prostate cancer. Localised prostate cancer was defined as cT1–cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1–cT2, or as any T‐stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus‐based or evidence‐based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.

Michelle Lancee, Kari A.O. Tikkinen, Theo M. de Reijke, Vesa V. Kataja, Katja K.H. Aben and Robin W.M. Vernooij

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Article of the Week: Oncological outcomes and toxicity for LDR prostate brachytherapy

January 3, 2018/by admin Z.9

Every Week the Editor-in-Chief selects an 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.

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.

If you only have time to read one article this week, it should be this one.

Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer

Stephen E. M. Langley, Ricardo Soares, Jennifer Uribe, Santiago Uribe-Lewis, Julian Money-Kyrle, Carla Perna, Sara Khaksar and Robert Laing

St Luke’s Cancer Centre, Guildford, Surrey, UK

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Objectives

To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment.

Patients and Methods

Of 3262 patients treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3-years post-implantation follow-up and four prostate-specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer-specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician-reported adverse events and patient-reported symptom scores.

Results

The median (range) age was 57 (44-60) years, follow-up was 8.9 (1.5-17.2) years, and PSA follow-up 5.9 (0.8-15) years. Low-, intermediate- and high-risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low-risk, 99% and 100% for intermediate-risk, and 93% and 95% for high-risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low-, intermediate-, and high-risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment.

Conclusion

LDR brachytherapy is an effective treatment with long-term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment-related toxicity and can be considered a first-line treatment for prostate cancer in this patient group.

Editorial: LDR prostate brachytherapy in younger men

January 3, 2018/by admin Z.9

Langley et al.¹ report on the oncological and functional outcomes of men treated with low dose rate (LDR) prostate brachytherapy in men 60 years old or younger. 597 patients with a median (range) age of 57 (44-60) years had a median follow-up of 8.9 (1.5-17.2) years. The 10- year post-implant relapse free survival using the Phoenix definition for biochemical failure (nadir plus 2 ng/ml) was 95%, 90% and 87% for low, intermediate and high-risk disease, respectively. Potency was preserved in 75% of men potent before treatment. The authors concluded that LDR brachytherapy is an efficacious treatment with excellent long-term control of prostate cancer in men ≤60 years at time of treatment. While the results from this investigation are encouraging, enthusiasm should be tempered given the short follow up, long natural history of prostate cancer and the long-life expectancy for these younger patients.

Although the overall median follow-up was 8.9 years, the calculation of PSA-free failure was derived from a median follow-up of 5.9 years. As this investigation did not identify men who may also be at risk of failure because of a rising PSA and who have not yet reached the Phoenix threshold, I anticipate longer-follow up will further reduce their favorable results. Of the 597 men, 6 (1%) died from prostate cancer. The low incidence of prostate cancer mortality, while impressive, also reflects the short follow-up. Our group has previously reported that PCSM substantially increases between the 10th and 15th year post treatment. The experience of these physicians in prostate brachytherapy is demonstrated in their favorable dosimetry outcomes-the median D90 was 106.4% of the prescription (145 Gy). These results (median D90 154.3 Gy), which were determined and computed on the day of the implant would be 10-15% higher had the CT scans been done on day 30 as most centers do. We and others have reported that patients receiving higher dose implants have improved biochemical and cancer-specific outcomes. While these data help explain their favorable oncological outcomes, they should also serve as a guide to other brachytherapy programs where implant quality should be a primary objective. Erectile function was preserved in 75% of men. These data are consistent with other reports of younger men who were treated for prostate cancer with surgery or radiation. Because this was not a randomized study, it is not possible to make direct comparisons between surgery and brachytherapy. The selection of an IIEF score of > 11 as potent might be challenged as the 12-16 group is considered to have mild to moderate ED. Nonetheless, these data are still encouraging for younger men who are considering treatment for localized prostate cancer where sexual function preservation is important.

Nelson Stone

Mount Sinai Medical Center – Urology 350 E 72nd Street, New York, New York 10021 United States

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Reference

Langley SM, Soares R, Uribe J, et al. Long-term oncological outcomes and toxicity in 597 men ≤60 years of age at time of low dose rate brachytherapy for localised prostate cancer. BJU Int 2017

RE: Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy

May 9, 2016/by admin Z.9

Sir,

Thank you for your interest in our article regarding whole-gland brachytherapy to the prostate for prostate cancer (1). Your letter is highlighting the expanding role of brachytherapy to that of focal therapy (2). We agree that multiparametric magnetic resonance imaging (mpMRI) scans have expanded the ability to localise tumours and indeed that they may be useful in carefully selected men wishing to undergo focal therapy. However, other advances such as the use of fiducial markers and spacers have also allowed better dosimetry and for a reduction in side effects (3). The safety and performance of brachytherapy in whole gland treatment means we should have faith in it as a modality to destroy cancer on the focal therapy setting. There are new trials being developed with focal brachytherapy and we look forward to the results in the coming years.

References

Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int 2015; 116(S3): 80-8. doi: 10.1111/bju.13252.

Nguyen PL, Trachtenberg J, Polascik TJ. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol. 2014 Oct;66(4):732-51. doi: 10.1016/j.eururo.2013.05.048. Epub 2013 Jun 6. Review.

Ng M1, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. BJU Int. 2014 Mar;113 Suppl 2:13-20. doi: 10.1111/bju.12624. Fiducial markers and spacers in prostate radiotherapy: current applications.

Letter to the Editor

Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy

Sir,

I have recently read, with high interest, the review article “Brachytherapy: state-of-the-art radiotherapy in prostate cancer”, by Chao et al.[1]. The authors made extremely clear the advanced technologies of computerized treatment planning and imaging-guided delivery modalities to reach a tailored ablative prostate tumor target dose by resorting to either low-dose-rate (LDR) or high-dose-rate (HDR) different brachytherapy procedures as regards three basic – low, intermediate, high – disease risk classificative conditions.

It is today proven that focal instrumental procedures inside the prostate gland – from biopsy to various prostate cancer focused ablative strategies, among which laser interstitial thermal therapy and particularly the prostate cancer brachytherapy – might require the resort to proper software digital overlay-mediated fusion of both beforehand multiparametric magnetic resonance imaging (mpMRI) scans and later real-time transrectal 3D ultrasound findings. Like this, indeed, intriguing developments in software modelling techniques have led to reach, by a mpMRI-ultrasound image fusion approach, more accurate targeted prostate cancer biopsies than those by transrectal ultrasound imaging alone achieved [2,3].

If the transperineal focal laser prostate tumor ablation usually occurs only with the guidance of mpMRI (T2-weighted, diffusion-weighted, dynamic contrast material) [4], as regards the prostate cancer brachytherapy, instead, it is more and more timely, for just targeting the tumor “index-dominant lesion”, the resort to mpMRI/transrectal real-time ultrasound fusion imaging. Quite recently, mpMRI/real-time transrectal ultrasound software-mediated digital co-registration has allowed to properly carry-out, in patients suffering from intermediate/high risk prostate carcinoma with mpMRI visible “index- dominant” intraprostatic nodule, the HDR ¹⁹² Ir transperineal temporary implant-brachytherapy as accurate partial prostate radiation dose escalation supplemental to hypofractionated external beam radiotherapy [5,6].

Given the interesting, even rare, reports on this subject, it would be advisable to widen the resort to the above-outlined mpMRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy, particularly for a suitably targeted dominant tumor nodule detection/ablation.

Contardo Alberti

L D of Surgical Semeiotics, University of Parma, Parma, Italy

References

1 Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int 2015; 116(S3): 80-8. doi: 10.1111/bju.13252.

2 Shoji S, Hiraiwa S, Endo J, Hashida K, Tomonaga T, Nakano M et al. Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and stransrectal ulrasound :an early experience. Int J Urol 2015; 22(2): 173-8. doi: 10.1111/iju.12643.

3 Marks L, Young S, Natarajan S. MRI-ultrasound fusion for guidance of targeted prostate biopsy. Curr Opin Urol 2013; 23(1): 43-50. doi: 10.1097/MOU.0b013e32835ad3ee.

4 Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Magnetic resonance-guided thermal therapy for localized and recurrent prostate cancer. Magn Reson Imaging Clin N Am.2015; 23(4): 607-19. doi:10.1016/j.mric.2015.05.014

5 Bubley GJ, Bloch BN, Vazquez C, Genega E, Holupka E, Rofsky N, Kaplan I. Accuracy of endorectal magnetic resonance/transrectal ultrasound fusion for detection of prostate cancer during brachytherapy. Urology 2013;81(6): 1284-9. doi: 10.1016/j.urology.2012.12.051.

6 Gomez-Iturriaga A, Casquero F, Urresola A, Ezquerro A, Lopez JI, Espinosa JM et al. Dose escalation to dominant intraprostatic lesions with MRI-transrectal ultrasound fusion high-dode-rate prostate brachytherapy. Radiother Oncol 2016 Feb 15. doi: 10.1016/j.radonc.2016.02.004 (Epub ahead of print).

Article of the Week: Assessing prostate cancer brachytherapy using patient-reported outcomes

October 8, 2014/by admin Z.9

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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. James Talcott discussing his paper.

If you only have time to read one article this week, it should be this one.

Using Patient-Reported Outcomes to Assess and Improve Prostate Cancer Brachytherapy

James A. Talcott 1, 2, 10, 11, Judith Manola 3, Ronald C. Chen 4, Jack A. Clark 5, 6, Irving Kaplan 7, 8, Anthony V. D’Amico 8, 11 and Anthony L. Zietman 9, 11

1 Massachusetts General Hospital Cancer Center, Boston, MA, 2 Continuum Cancer Centers of New York, New York, NY, 3 Dana-Farber Cancer Institute, Boston, MA, 4 Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 5 Center for Health Quality, Outcomes, and Economic Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, 6 Boston University School of Public Health, 7 Beth Israel-Deaconess Medical Center, 8 Brigham and Women’s Hospital, 9 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 10 Albert Einstein School of Medicine, New York, NY, and 11 Harvard Medical School, Boston, MA, USA

Read the full article

OBJECTIVE

To describe a successful quality improvement process that arose from unexpected differences in control groups’ short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity.

PATIENTS AND METHODS

Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study.
Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals.
Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT₁ and US-BT₂). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change.

RESULTS

The patient groups were demographically and clinically similar.
In the first preliminary analysis, US-BT₂ patients reported significantly more short-term post-treatment urinary symptoms than US-BT₁patients.
The studies treating physicians reviewed the US-BT₁ and US-BT₂ treatment protocols and found that they differed in whether they used an indwelling urinary catheter.
After adopting the US-BT₁ approach, short-term urinary morbidity in US-BT₂ patients decreased significantly. Brachytherapy procedures were otherwise unchanged.

CONCLUSION

Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care.
We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care.

Editorial: Patient-reported outcomes – a force for clinical improvement or another way for ‘big brother’ to survey clinicians?

October 8, 2014/by Alastair Henderson

In the 19th century Lord Kelvin wrote, ‘If you cannot measure it, you cannot improve it’. Since then clinical improvement has often been about measuring outcomes to determine what elements of healthcare are working well and what can be improved. The early studies of antisepsis and surgical technique had endpoints, which were measured by doctors deciding whether a wound infection, cancer recurrence or even death had occurred. These outcomes were usually discrete with little room for describing states between success and failure.

In this era whether the patient perceived that the treatment had been successful or not was irrelevant to the ‘success’ of treatment providing that the medical world agreed that the treatment had been a success. As treatments have become more established and the medical and pharmaceutical world has become more patient focussed, interest has increased in how patients report the outcome of treatment, often using questionnaires.

The pioneers of this work were mainly psychiatrists concerned about patient anxiety and depression [1] and clinical oncologists, aware that multimodal chemoradiotherapy treatments, which might in many cases be offered with palliative rather than curative intent, had the potential to cause a net loss in quality of life even if patients lived a short time longer on treatment.

As these patient-reported outcome measures (PROMs) became more commonly used in clinical trials, their focus has extended to quite specific outcomes, such that in the current era it is unusual to see papers on LUTS or erectile function presented that do not use validated PROMs, such as the IPSS [2] or International Index of Erectile Function (IIEF) [3].

The current era of research is starting to make new use of the data sources that are useful both as absolute values relating to the severity of symptoms but also particularly in measuring change in level of symptoms. Hard outcomes, such as death from cancer, have been found to be related to patient reported quality of life at presentation [4].

Clinicians are now starting to develop the necessary skills to analyse PROMs. In this setting Talcott et al. [5] have used PROM data to identify unexpected variances in symptomatic outcome after prostate brachytherapy. This was an unexpected post hoc analysis of a difference in outcomes between the two control groups in a study. It found that there was a significant difference in outcome between patients who had received an implant in two centres, which might have been expected to have similar outcomes. Analysis of differences in the implant technique in the two institutions suggested that the use of a urethral catheter to clearly visualise the urethra might be the difference and modification of this part of the technique resulted in similar PROMS outcomes in both institutions.

This is a novel quality improvement approach, which may become more widespread as institutions more frequently collect, analyse and present their PROMS. The bio-informatics skills needed to analyse this type of data meaningfully may become a greater part of everyday practice in the modern era, especially for the ‘index’ most common operations in surgical specialities. It would be interesting to see what a similar approach would produce if variance in PROMs after transurethral prostate surgery were analysed between centres in the UK and USA. Organisations with a track record for effective data analysis and reporting such as Dr Foster will be watching this evolve.

Read the full article

Alastair Henderson

Maidstone and Tunbridge Wells NHS Trust, Department of Urology, Maidstone Hospital, Maidstone, Kent, UK

References

1 Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiat Scand 1983; 67: 361–70

2 Barry MJ, O’Leary MP. Advances in benign prostatic hyperplasia. The developmental and clinical utility of symptom scores. Urol Clin North Am 1995; 22: 299–307

3 Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH. Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 1999; 54: 346–51

4 Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health Qual Life Outcomes 2009; 7: 102

5 Talcott JA, Manola J, Chen RC et al. Using patient-reported outcomes to assess and improve prostate cancer brachytherapy. BJU Int 2014; 114: 511–6

Video: PROs in Prostate Brachytherapy

October 8, 2014/by admin Z.9

Using Patient-Reported Outcomes to Assess and Improve Prostate Cancer Brachytherapy

James A. Talcott 1, 2, 10, 11, Judith Manola 3, Ronald C. Chen 4, Jack A. Clark 5, 6, Irving Kaplan 7, 8, Anthony V. D’Amico 8, 11 and Anthony L. Zietman 9, 11

Read the full article

OBJECTIVE

To describe a successful quality improvement process that arose from unexpected differences in control groups’ short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity.

PATIENTS AND METHODS

Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study.
Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals.
Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT₁ and US-BT₂). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change.

RESULTS

The patient groups were demographically and clinically similar.
In the first preliminary analysis, US-BT₂ patients reported significantly more short-term post-treatment urinary symptoms than US-BT₁patients.
The studies treating physicians reviewed the US-BT₁ and US-BT₂ treatment protocols and found that they differed in whether they used an indwelling urinary catheter.
After adopting the US-BT₁ approach, short-term urinary morbidity in US-BT₂ patients decreased significantly. Brachytherapy procedures were otherwise unchanged.

CONCLUSION

Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care.
We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care.