SIU 2018: Management of Grade Group 2 Prostate Cancer, Radical Therapy

Seoul, South-Korea ( In this session, a case of intermediate risk prostate cancer was presented and various treatment options were discussed. In this specific session management with radical therapy was recommended. The hypothetical patient was a 65-year-old healthy man, who is a non-smoker, with mild hypertension, and a mild decrease of erectile function with an International Prostate Symptom Score (IPSS) of 12. He had a positive family history with his father being diagnosed with prostate cancer at age 75 and treated with brachytherapy in 2005.  This man had a normal digital rectal examination (DRE), showing a 40 cc prostate gland. His PSA is 5.5 ng/ml (increased from 3 ng/ml in 2015, to 4.2 ng/ml in 2017). His transrectal ultrasound (TRUS) demonstrated a 45 cc prostate. He underwent a systematic biopsy demonstrating Gleason 7 (3+4) in 2/12 cores, in the right peripheral zone, with 10% pattern 4, and 20% core involvement. Additionally, the biopsy demonstrated a Gleason 6 (3+3) lesion in the right apex peripheral zone with 15% core involvement. Lastly, the patient underwent a multiparametric MRI of the prostate demonstrating a 13 mm PIRADS 3 right mid posterior peripheral zone lesion.

Dr. Fleshner gave his perspective supporting treatment with radical therapy for this patient, either in the form of radiotherapy or radical surgery. Dr. Fleshner believes that our ultimate goal of therapy should be cancer control in 15-20 years and preservation of quality of life. When assessing the metastasis-free survival in 15 years after diagnosis of prostate cancer, in grade group 1 it is 94%, in grade group 2 it is 84%, and in grade group 3 it is 63%. This mandates that grade group 2 patients be treated in some active way, in order for them to be free of disease in 10-15 years. This is the proof that active surveillance is not a suitable option for these patients.

Focal therapy has advantages in that it is possible to treat the dominant lesion in a satisfactory way, and there is some biological evidence demonstrating that the dominant lesion is behind most, if not all metastasis development. However, prostate cancer is known to be a multifocal disease with an average of 5.1 tumors per prostate, according to some data derived from radical prostatectomies. When looking at some of the published series on focal therapy, it is important to note that despite the very good functional results obtained with focal therapy, the recurrence rate is not negligible, varying from 8% to 23%, seen in biopsies done 6-12 months following treatment. Dr. Fleshner showed recently published focal therapy data from the Princess Margaret Hospital, of 166 patients treated with focal therapy with a median follow-up of 24.3 months. This date demonstrated a recurrence rate of 42%, with medially located tumors being at a higher risk.1

Results from the first prospective study on focal treatment in the form of HIFU, by Conort P. et al. on 117 patients with a minimum of five years of follow-up, demonstrated a success rate of 75%, with a re-treatment rate of 39%, and a need for adjuvant treatment in 22% of patients. 2                   

Focal HIFU entails great functional results with high rates of continence and potency preservation. Surgical treatment following HIFU focal therapy is essentially feasible with minimal downside. However, we still lack the knowledge regarding the optimal technique to use in focal HIFU, and we still do not possess the true long-term success rates of this therapy. Data from the Princess Margaret Cancer Center regarding salvage surgery following HIFU focal therapy, presented at the AUA  in 20183, demonstrated  that out of 34 patients undergoing radical prostatectomy following HIFU treatment, 91.2% reported use of one pad per day due to urinary incontinence, one patient required an artificial urethral sphincter, and 53% reported having erections with PDE-5 inhibitors. Moreover, almost 30% of patients had positive surgical margins after surgery, and two patients had incidental intraoperative cystotomies.

Dr. Fleshner then moved on to discuss the advantages of radical prostatectomy as a definitive therapy for patients with grade group two disease. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer after a median follow-up of 10.8 years was published.3  This study demonstrated a clear advantage for radical prostatectomy in overall survival, prostate cancer-specific death, and metastasis. When looking at the long-term quality of life (12.2 years), it was surprisingly quite comparable between radical prostatectomy and watchful waiting (35% vs. 34%), with similar potency rates (84% vs. 80%), but higher urinary incontinence issues (41% vs. 11%). 4

Dr. Fleshner summarized his talk, stating that for patients with grade group two disease, active surveillance is an unsafe management strategy, and focal therapy is lacking relevant and long-term data. In contrast, radical therapy has substantiated validated good long-term data, and suitable for men of all ages.

Presented by: Neil Fleshner, MD, Princess Margaret Cancer Center, Toronto, Canada

1. Bass R. et al. J Urol 2018
2. Conort P. et al. Eur Urol Suppl 2008
3. JNCI 2008; 100: 1144-1154
4. Johansson et al. Lancet Oncol 2011
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre  Twitter: @GoldbergHanan at the 38th Congress of the Society of International Urology - October 4- 7, 2018 - Seoul, South Korea

Further Related Content:
Management of Grade Group 2 Prostate Cancer, Surveillance