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ASCO GU 2020

ASCO GU 2020: Individualized Approaches to Treatment in Localized Prostate Cancer

San Francisco, California (UroToday.com) At the localized prostate cancer session at ASCO GU on individualizing diagnosis, staging, and treatment, Adam Kibel, MD, discussed individualized approaches to the treatment of localized prostate cancer. When managing localized prostate cancer, whether the patient is low, intermediate or high-risk, the most important consideration is to select the right patient for the right treatment. Patient selection includes grade, stage, tumor volume, genetics, genomics, and MRI. Treatment selection includes the side effects of treatment, health of the patient, patient goals, and the aggressiveness of the disease. 


Management of low risk prostate cancer should be active surveillance and being sure to identify those that are not truly low-risk who may benefit from treatment. Dr. Klotz’s long-term follow-up of a large active surveillance cohort form Toronto comprising 993 men demonstrated that over 15 years of follow-up, 267 patients were treated, 28 patients had metastatic disease, 15 deaths resulted from prostate cancer, 10 year CSS was 98% and 15 year CSS was 94%.1 According to Dr. Kibel, the patient’s genetic profile is most important. In the 2016 landmark study by Pritchard et al.2 692 men with metastatic prostate cancer had their genome sequenced, identifying 84 germline DNA-repair gene mutations, which were present in 11.8% of men, most commonly BRCA2. In a study from last year, Dr. Carter assessed genetics (ATM and BRCA1/2 mutations) of 1,211 men on active surveillance.3 Of 1211 men, 289 patients experienced grade reclassification; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers (adjusted HR 1.96, 95% CI 1.004-3.84, p=0.04). Furthermore, reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers (adjusted HR 2.74, 95% CI 1.26-5.96, p=0.01). Dr. Kibel notes that only 2% of patients had mutations and he does not think that all patients have to be tested as of now. Rather, men with a family history of lethal prostate cancer are likely not ideal candidates for active surveillance. 

The integration of MRI has become important in the assessment of localized prostate cancer in recent years. The PRECISION trial randomized men to MRI plus biopsy versus a 12 core biopsy alone, finding clinically significant prostate cancer among 38% of men undergoing MRI followed by targeted biopsy compared to 26% for men undergoing standard biopsy.4 According to Dr. Kibel it is logical that MRI would help in active surveillance and retrospective data supports its use in active surveillance. However, Dr. Kibel notes that the Dr. Klotz led ASIST trial may have somewhat tempered the utilization of MRI in active surveillance.5 This trial randomized 273 men with Gleason 6 prostate cancer to 12 core biopsy versus 12 core biopsy plus an MRI. At one year, 23% were upgraded on systematic biopsy alone, compared to 21% with systematic biopsy plus MRI. Dr. Kibel notes that he still uses MRI but this does raise concern about its overutilization. 

For patients with intermediate risk disease, an MRI is important for determining occult high-grade cancer (GG3 or greater) which must be biopsy confirmed – we cannot act on the MRI alone. Dr. Kibel notes that this is a perfect place to utilize genomics, which may help determine the molecular signature of aggressive cancer. In a multicenter study of 6,928 robotic prostatectomy patients that underwent a Decipher test with a median follow-up of 8 years, 10-year distant metastasis rates for NCCN low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively.6 In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively. C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61-0.93) were improved over NCCN (0.73; 95% CI, 0.60-0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65- 0.84). 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. As such, favorable intermediate risk patients could be classified as low risk and be offered active surveillance, whereas favorable intermediate risk reclassified to genomic unfavorable intermediate risk could be offered treatment. 

Dr. Kibel concluded his presentation with several take home points:

  • The most important information is stage, grade, and tumor volume
  • MRI’s are useful but maybe not as much as we think
  • Genomics can be helpful in the right patient
  • It is important to tailor treatment based on an integrated assessment: low risk men should be offered active surveillance, intermediate risk should be offered radiation or surgery, and high-risk men should undergo multimodality treatment or clinical trials

Presented by: Adam S. Kibel, MD, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA 

Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

References:

  1. Klotz L, Vesprini D, Sethukavalan P, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol 2015;33(3):272-277.
  2. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453.
  3. Carter HB, Helfand B, Mamawala M, et al. Germline mutations in ATM and BRCA1/2 are associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer. Eur Urol 2019 May;75(5):743-749.
  4. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate cancer diagnosis. N Engl J Med 2018;378(19):1767-1777.
  5. Klotz L, Loblaw A, Sugar L, et al. Active surveillance magnetic resonance imaging study (ASIST): Results of a randomized multicenter prospective trial. Eur Urol 2019;75(2):300-309.
  6. Spratt DE, Zhang J, Santiago-Jimenez M, et al. Development and validation of a novel integrated clinical-genomic risk group classification for localized prostate cancer. J Clin Oncol 2018 Feb 20;36(6):581-590.