Steven Joniau Filip Ameye Implementation of nomograms into clinical practice Steven Joniau Filip Ameye

Clinical value of nomograms Important role in the process of decision aid and patient counseling Predictive accuracy Statistical vs clinical significance Accuracy Increase of 12% = 120 out of 1000 patients are provided with accurate prediction Medical, ethical, economical,… implications Uplevelling by introduction of novel biomarkers

Why should we use nomograms? Nomograms have been developed to accomodate stage migration Not only take into account PSA, Gleason score, clinical stage Also account for number of biopsies, prior biopsies, etc. Use updated data sets Should be validated, ideally by external validation

Predictive accuracy of existing nomograms Chun F et al. World J Urol 2007

86% 11% 3% Question: Are you? Urologist Radiation oncologist Medical oncologist Urologist Radiation oncologist Medical oncologist 86% 11% 3% You have 10 seconds

Question for Urologists: do you have access to robot-assisted surgery ? Yes No Yes No 37% 63% You have 10 seconds

Clinical case 62 years old, married, sexually active First PSA: 13.5 ng/ml. PSA years before 9 ng/ml DRE: nodule of the right prostatic lobe T3a

Clinical case Large hypoechoic zone in postero-basal right 12 biopsies Right side: 6/6 positives in 3 sextants Gleason 3+4 Left side : 2/6 positives Gleason 4+4

Final stage is T3a N0 M0 Final stage is T3a N0 M0 Question: What are the chances this patient has extraprostatic extension ? 25% 50% 75% 100% 25% 50% 75% 100% 20% 38% 39% 3% You have 10 seconds

Partin tables are not appropriate for staging T3a cancers!!! NCCN, Practice Guidelines in Oncology, 2005 10

T3 pre-treatment table 200 pts with clinical unilateral T3a disease - RP and bilateral LN dissection Gleason pT stage PSA (ng/mL) ≤ 10 10 – 20 ≥ 20 ≤ 7 (3+4) pT2 29 (20-39) 21 (12-33) 14 (5-27) pT3a 65 (55-74) 63 (49-76) 46 (30-62) pT3b 5 (2-10) 14 (5-24) 32 (18-48) pT4 1 (0-2) 2 (0-8) 8 (0-16) ≥ 7 (4+3) 31 (15-46) 20 (7-36) 9 (2-21) 54 (37-71) 47 (30-65) 23 (9-43) 12 (4-25) 26 (12-46) 44 (19-69) 3 (0-10) 7 (0-17) 24 (0-55) Moet besteld Joniau S et al. Eur Urol 2007;51:388–96 11

Final stage is T3a N0 M0 Final stage is T3a N0 M0 Question:What are the chances this patient has lymph node involvement ? < 10% 10 – 20% 20 – 50% > 50% < 10% 10 – 20% 20 – 50% > 50% 11% 43% 43% 0% 3% You have 10 seconds

Nomogram: Kattan MSKCC Memorial Sloan Kettering Cancer Center Web Site 13

A small exercise… Patient XY PSA 6.4 cT2a Biopsy Gleason score 6 on biopsies

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of biochemical relapse after surgery… 25% 50% 75% 100%

What is the risk of biochemical relapse after surgery… 25% 50% 75% 100%

A small exercise… Patient YY PSA 8.6 cT2c Biopsy Gleason score 7 on biopsies

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of… ECE? SVI invasion? pN+? 20% 40% 60% 80% 20% 40% 60% 80% SVI invasion? 5% 10% 15% 20% pN+? 2% 4% 6% 8%

What is the risk of biochemical relapse after surgery… 25% 50% 75% 100%

What is the risk of biochemical relapse after surgery… 25% 50% 75% 100%

EAU prostate cancer guidelines Use of nomograms is only included 3 times Preoperative staging (Kattan nomogram, Partin tables (= look-up tables)) Indication of extended lymph node dissection (Briganti nomogram) Indication of nerve-sparing surgery (Partin tables)

So, clearly the use of nomograms has not yet been implemented sufficiently into routine urological practice!!!!! The reason for this is that studies providing EBM on the advantage of using nomograms over clinical judgement are virtually ABSENT!!!

Why should nomograms be implemented into clinical practice? Appropriate patient couseling and decision-making Better disease prognostication Follow-up scheduling Selection of appropriate patients for clinical trials

Why should nomograms be implemented into guidelines? Currently, the only method through which we can compare biochemical recurrence rates after alternative treatment modalities with brachytherapy, external beam radiotherapy, and radical prostatectomy are nomograms

What do we need in the future? Update nomograms to contemporary situation Head-to-head comparisons between nomograms to select the best-suited model in selected fields of PCa outcomes We need nomograms that provide accurate predictions of hard clinical endpoints (clinical failure, death from the disease) We need nomograms that accurately predict death from comorbid disease in men with localized disease selected for radical treatment We need nomograms that predict treatment-related toxicity

What do we need in the future? Ultimately, improved imaging studies and high-throughput genomics may replace the use of nomograms, as they will provide an real patient-specific staging and prognostication, and patient-tailored treatment decisions In the meantime, nomograms are the best possible alternative and should be actively implemented in urological practice