ANZUP Mini ASM 2020: Multi-Disciplinary Tumor Master Games - Early Stage Prostate Cancer

(UroToday.com) To begin the scientific portion of The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting (ASM) held 29 – 30 November 2020, Drs. Craig Gedye, Carole Harris, and Nicky Lawrence convened a session entitled Multi-Disciplinary Tumor (MDT) Master Games which sought to cover relevant and controversial topics in the management of urologic cancers.

The first talk within this session was led by Dr. Nadine Beydoun, examining controversial aspects of the care of patients with early-stage prostate cancer with panelists including Dr. Joseph Bucci (radiation oncologist focussing on brachytherapy), Dr. James Thompson (urologist), Miss Pauline Thomson (a clinical nurse coordinator), and Miss Sharyn Wappett (a physiotherapist with a focus on exercise oncology and pelvic floor health).

Dr. Bedouyn began with a case of a 63-year-old man with an elevated prostate-specific antigen (PSA) of 6.8 ng/mL, normal digital rectal exam, prostate volume of 40cc on transrectal ultrasound, and no significant lower urinary tract symptoms. She polled the audience regarding next steps, offering choices including biopsy, MRI, prostate-specific membrane antigen (PSMA) PET, or return to the general practitioner. The vast majority of the audience suggested MRI as the next most appropriate step.

This patient then underwent magnetic resonance imaging (MRI) demonstrating a 32cc gland with a PIRADS 5 lesion at the right posterolateral base, measuring 10 x 17mm and abutting the capsule.



Dr. Beydoun then again asked what step should next be undertaken, highlighting the potential for biopsy or PSMA-PET/CT. 93% of audience members recommended a biopsy-based approach which is what this patient received. Dr. Thompson did discuss the role of pre-biopsy PSMA-PET/CT: this approach is currently being evaluated in the PRIMARY trial with the use of Gallium-68 PSMA-PET/CT in patients with equivocal MRI findings (PIRADS 3) with the goal of avoiding biopsy in patients with negative PSMA-PET/CT. Results of this trial are expected in the near future.

In this case, the patient underwent transperineal prostate biopsy demonstrating Gleason 3+4=7/ISUP 2 prostate adenocarcinoma in 26/42 cores. He subsequently underwent PSMA-PET/CT for staging which demonstrated mild, heterogeneous uptake in the posterior prostate base (SUV 3.8), without evidence of distant spread. Dr. Thompson suggested, and Dr. Bucci concurred, that staging investigation may not be necessary in this patient.

Dr. Beydoun then highlighted this gentleman’s past medical history, as it may be relevant to treatment choices.

In this case, the patient had good urinary function without evidence of obstruction and sexual function was of the utmost importance. Dr. Beydoun then asked the audience their preference regarding treatment options, with the majority recommending radical prostatectomy.

Dr. Thompson and Dr. Bucci then provided their feedback. Given a relative lack of life-limiting conditions, Dr. Thompson suggested that surveillance would not be appropriate for this gentleman, and he would recommend active treatment. Dr. Bucci concurred that active treatment would be most appropriate, with clear targets for conversion to active therapy.

Dr. Thompson was asked about counseling for a surgical approach. He emphasized that counseling for post-operative erectile function depends in large part on his baseline erectile function. Given his MRI lesion, Dr. Thompson suggested a left-side nerve spare and potentially a partial nerve spare on the right would be feasible but that men should anticipate a decline in erectile function in any case. Dr. Bucci highlighted that all treatments are associated with sexual dysfunction. He highlighted that 25-50% of patients treated with brachytherapy will have significant impotence.

In a patient who prioritizes maintaining erectile function, Dr. Bucci suggested that brachytherapy and radical prostatectomy should be considered. Additionally, he highlighted the potential for focal therapy, including in the context of the ongoing POWER study which is randomizing to hemi-gland vs. whole-gland brachytherapy for patients with unilateral disease, powered to assess sexual dysfunction rates. For patients considering external beam radiotherapy, Dr. Bucci recommended the use of 6 months of androgen deprivation therapy (ADT) for patients with unfavorable intermediate-risk prostate cancer, highlighting that he would be willing to spare androgen deprivation in patients undergoing brachytherapy.

Dr. Beydoun then discussed the use of Stereotactic Body Radiotherapy (SBRT) to emulate brachytherapy (NINJA trial) in so-called “virtual brachytherapy”. Patients with unfavorable intermediate-risk or high-risk disease are being randomized to SBRT monotherapy (40 Gy in 5 fractions) or virtual HDR brachytherapy boost (20 Gy in 2 fractions followed by 12 fractions). Dr. Bucci highlighted that there is a lack of a standard control with conventional brachytherapy in this trial and that, despite the “virtual brachytherapy”, patients still require a procedure for fiducial marker placement and rectal spacer placement.

An audience member raised the question of pelvic lymph node dissection – Dr. Thompson pointed out that surgical dogma has supported the role of node dissection though data to support a survival benefit has yet to be demonstrated. Dr. Bucci highlighted that question exists in the radiation oncology literature as well – with limited evidence for the benefit of elective pelvic nodal irradiation.

Dr. Beydoun then asked Miss Sharyn Wappett (physiotherapist) about the management of urinary toxicity. She highlighted the importance of teaching pelvic floor exercises preoperatively in patients undergoing radical prostatectomy. In patients undergoing radiotherapy, she emphasized the management of the associated overactivity with bladder training.

Dr. Beydoun then presented a second case, of a 69-year-old man with rising PSA. Following initial MRI with a PIRADS 3 lesion, biopsy demonstrated a relatively low volume of Gleason 3+3=6/ISUP 1 prostate cancer.

She then polled the audience regarding treatment options with most suggesting the surveillance would be appropriate.

Notably, Dr. Beydoun highlighted a discordance between the MRI and biopsy results. Dr. Thompson highlighted the importance of the quality of MRI interpretation in guiding treatment, given significant inter-reader variability. He highlighted some of his own data which demonstrated that serial surveillance MRI can be informative – repeated PIRAD4 is associated with high rates of clinically significant cancer while reversion to lower PIRAD scores is associated with lower risks of clinically significant disease.

Moving forward with the case, Dr. Beydoun presented that 6 months later the patient underwent a repeat MRI and biopsy, demonstrating multiple PIRADS 2 lesions but Gleason 4+3=7/ISUP 3 prostate cancer in 3/32 cores. Subsequent conventional staging demonstrated no evidence of nodal involvement or metastasis. On polling, the audience was split with respect to treatment approaches.

Dr. Beydoun agreed with the audience that a better understanding of the patient context is important before moving forward. Miss Pauline Thomson (a clinical nurse coordinator) highlighted the importance of patient work-up and selection when considering potential brachytherapy. In particular, in their clinic, they utilize a central pathology review of biopsy results, staging and uroflow, and bladder scan to rule out obstruction. Dr. Bucci further emphasized the importance of assessment and counseling with respect to urinary dysfunction associated with brachytherapy. Thus, they seek to highly select patients prior to brachytherapy, including the use of cystoscopy at the time of evaluation as well as potential median lobe resection prior to implant.

In the context of this patient's care, Dr. Beydoun provided further medical history, most notable for AML which he had relatively recently undergone chemotherapy.

This patient did not prioritize erectile function, given both the nature of his inter-personal relationships and the toxicity of his AML therapy. In deciding on how to move forward, both Dr. Thompson and Dr. Bucci emphasized the importance of understanding the prognosis associated with this patient’s AML, through consultation with his hematologist. Dr. Thompson suggested that if there is a generally poor prognosis, a period of observation may be suitable. If, however, long term outcomes of AML are deemed favorable, based on the prostate cancer characteristics, curative intent therapy would be appropriate. Dr. Bucci emphasized that there are unlikely to be differences in outcome or toxicity between radiotherapy modalities, regardless of comorbidity.

Presented by: Chair: Nadine Beydoun, MBBS, FRANZCR, Fellow of the Royal Australian and New Zealand College of Radiologists (Faculty of Radiation Oncology), member of the America Brachytherapy Society, the Australasian Brachytherapy Group, and The European Society for Therapeutic Radiation Oncology, NSW, Genesis Cancer Care 
Panelists: Joseph Bucci, MBBS FRACP FRANZCR, radiation oncologist, Genesis Care, Hurstville, NSW, senior lecturer at the University of NSW and University of Wollongong
James Thompson, BSc (Med) MBBS (Hons), FRACS, Ph.D., IMGSS Robotic Oncology Fellow, Royal College Surgeons (Ed), UCLH, Hurtsville, NSW Australia
Pauline Thomson, clinical nurse coordinator, St. George Hospital Cancer Care Centre, NSW Australia
Sharyn Wappett, BAppSc, physiotherapist, Hurtsville, NSW, Australia