Case Discussions: Prostate Cancer

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1 Case Discussions: Prostate Cancer Andrew J. Stephenson, MD FRCSC FACS Chief, Urologic Oncology Glickman Urological and Kidney Institute Cleveland Clinic

2 Elevated PSA 1 54 yo, healthy male, family Hx of prostate cancer (father, age 64) CC: Rising PSA Negative TRUS/Bx x 3 (2006, 2008, 2009), including recent 28- core saturation biopsy under anesthesia (reviewed at CCF) No HG PIN, no ASAP in any biopsy specimen PSA history: DRE: normal TRUS volume: 23 cc (PSA Density 0.3) 03/ / / / (F:T 7%) (F:T 5%) 5.21

3 Elevated PSA 1 By PCPT risk calculator: Prostate cancer: 42% Biopsy Gleason 7-10: 8% though neg TRUS/Bx x 3! or Google PCPT risk calculator

4 Elevated PSA 1 Treatment options: FU with PSA In 1 year? In 4 years as per ERSPC? Urine PCA3 5-alpha reductase inhibitor as chemoprevention Finasteride? Dutasteride? Does it matter? Endorectal coil prostate MRI Repeat TRUS/Bx How many cores? Location?

5 Elevated PSA 1 Patient recommended to undergo repeat TRUS/Bx Standard 14-core medially- and laterally-directed biopsy of each sextant (12) and bilateral TZ biopsy Specific focus on apical biopsy

6 Elevated PSA 1 Sagittal Coronal SV Base Mid Apex R. L. Presti JC Jr. Urol Oncol 2009

7 Elevated PSA 1 Sagittal Coronal SV Base Mid Apex R. L. Presti JC Jr. Urol Oncol 2009

8 Elevated PSA 1 Left Right Base 0/1 HG PIN 0/1 0/1 0/1 Mid Apex 1/1+ Glsn % 1/1+ Glsn % 1/2+ (TZ+) Glsn % 0/1 HG PIN 0/2 0/1 0/1 0/1 Lateral Medial Medial Lateral

9 Elevated PSA 1 Nomogram predictions: 10-year PFP with radical prostatectomy: 93% Risk of extraprostatic extension: Left 16% 5-year PFP with EBRT: 93% 5-year PFP with brachytherapy: 82% Patient elected to undergo bilateral NS-RALRP Pathology: Organ-confined, Gleason 3+4, margins negative, volume > 2 cc, 14 negative lymph nodes 10-year PFP by nomogram: 93%

10 Elevated PSA 1 Issues: Balancing early detection with over-diagnosis Role of 5-alpha-reductase inhibitors Chemoprevention Enhancing early detection Improves AUC of PSA and DRE for prostate cancer diagnosis PSA response to 5-ARI to determine need for biopsy?

11

12 Prostate Cancer 1 65 y.o., healthy male CC: Localized prostate cancer PSA history: 03/ / / / / PSA velocity: 0.36 ng/ml/yr since 2001 DRE: normal 3/14 cores positive, Gleason 6 TRUS volume 40 cc; PSA density: 0.11

13 Prostate Cancer 1 Left Right Base Mid 1/1+ Gleason 6 < 5% 0/1 1/1+ Gleason 6 < 5% 0/1 0/1 1/1+ Gleason 6 < 5% 0/1 HG PIN 0/1 Apex 0/1 0/1 0/1 0/1 ASAP Lateral Medial Medial Lateral

14 Prostate Cancer 1 PMH: Hypertension, hypercholesterolemia PSH: appendectomy Parents both lived into late 80 s No family history of prostate Ca Potent, good erections high priority No voiding dysfunction

15 Prostate Cancer 1 Low-volume, Gleason 6 prostate cancer, T1C, low PSA Nomogram Outcome Predictions: 10-year PFP with radical prostatectomy: 98% 5-year PFP with EBRT (81 Gy): 95% 5-year PFP with brachytherapy: 90% Nomogram Pathology Predictions: ECE: Right 6%, Left 5% SVI and LNI: < 2% Indolent cancer: 46% Epstein criteria for indolent Ca met (T1C, Gleason 6, PSAD < 0.15, 3 or fewer cores involved, none > 50% cancer per core)

16 Prostate Cancer 1 What would you recommend this patient? Open radical prostatectomy Robotic or laparoscopic radical prostatectomy External-beam radiation therapy Brachytherapy Active surveillance Other (HIFU, cryotherapy, focal therapy) Other?

17 Prostate Cancer 1 Patient chooses active surveillance due to quality-of-life concerns Recommended repeat biopsy patient chooses to do this in 6 months after wintering in Florida

18 Prostate Cancer 1 Patient chooses active surveillance due to quality-of-life concerns Recommended repeat biopsy patient chooses to do this in 6 months after wintering in Florida How do you survey patients on active surveillance? Frequency of follow-up PSA testing Need for re-biopsy? How often? Other imaging modalities?

19 Prostate Cancer 1 Patient chooses active surveillance due to quality-of-life concerns Recommended repeat biopsy patient chooses to do this in 6 months after wintering in Florida How do you survey patients on active surveillance? Frequency of follow-up PSA testing Need for re-biopsy? How often? Other imaging modalities? By what criteria do you recommend treatment? PSA kinetics? Grade progression? Increasing cancer burden? Change in prognosis (e.g. nomogram)?

20 Prostate Cancer 1 Patient returns in 6 mos for FU PSA history: 03/ / / / / / / PSA velocity: 1.16 ng/ml/year DRE: normal Nomogram unchanged (indolent Ca, PFP w/ Rx) Very happy, not anxious, still sexually active

21 Prostate Cancer 1 Left Right 1/2+ 1/1+ 1/2+ 0/1 Base Glsn 3+4 Gleason 6 Gleason 6 ASAP 5% 5% < 5% Mid 1/1+ Gleason 6 1/1+ Glsn 3+4 1/2+ Gleason 6 1/1+ Gleason 6 40% 60% 20% 5% Apex 0/1 0/1 0/1 0/1 Lateral Medial Medial Lateral

22 Prostate Cancer 1 7/17 cores positive, Gleason 3+4, T1c, PSA 5.3 Prognosis: Radical prostatectomy: 10-year PFP 84% EBRT: 5-year PFP 93% Brachytherapy: 5-year PFP 82% Pathological Staging: ECE: Right 6%, Left 9%

23 Prostate Cancer 1 What would you recommend this patient? Open radical prostatectomy Robotic or laparoscopic radical prostatectomy External-beam radiation therapy Brachytherapy Continued active surveillance Other (HIFU, cryotherapy, focal therapy) Other?

24 Prostate Cancer 1 Patient elected to undergo bilateral NS-RRP Final pathology: Established extraprostatic extension (bilateral), Gleason 3+4, negative margins, volume cc, 12 negative LN 10-year PFP by nomogram: 73% 8 wks postop: pad-free, erections adequate for intercourse with PDE5i, PSA NMA

25 Prostate Cancer 1 pt3a, Gleason 3+4, SM negative, PSA NMA Next step: Observation Adjuvant Radiotherapy Adjuvant ADT Observation and salvage radiotherapy at BCR Observation and ADT at BCR Other

26 Prostate Cancer 1 pt3a, Gleason 3+4, SM negative, PSA NMA Next step: Observation Adjuvant Radiotherapy Adjuvant ADT Observation and salvage radiotherapy at BCR Observation and ADT at BCR Other What if positive surgical margin?

27 Prostate Cancer 1 pt3a, Gleason 3+4, SM negative, PSA NMA Next step: Observation Adjuvant Radiotherapy Adjuvant ADT Observation and salvage radiotherapy at BCR Observation and ADT at BCR Other What if seminal vesicle invasion?

28 Prostate Cancer 1 pt3a, Gleason 3+4, SM negative, PSA NMA Next step: Observation Adjuvant Radiotherapy Adjuvant ADT Observation and salvage radiotherapy at BCR Observation and ADT at BCR Other What if detectable PSA level postop?

29 Prostate Cancer 1 Patient elected observation 2009: PSA NMA; continent, potent

30

31 Prostate Cancer 2 53 y.o. healthy male CC: Prostate cancer PSA history: 11/ / / / PSA velocity: 3.0 ng/ml/year DRE: nodules bilaterally, EPE+ (R. mid-base) Gleason 8, 12/12 cores positive, PNI+

32 Prostate Cancer 2 Left Right 1/1+ 1/1+ 1/1+ 1/1+ Base Glsn 4+3 Gleason 8 Glsn 3+4 Glsn % 80%, PNI+ 80%, PNI+ 100%, PNI+ Mid 1/1+ Gleason 8 1/1+ Glsn 4+3 1/1+ Glsn 3+4 1/1+ Glsn %, PNI+ 95%, PNI+ 60% 80%, PNI+ Apex 1/1+ Glsn 4+3 1/1+ Glsn 4+3 1/1+ Glsn 3+4 1/1+ Glsn % 95% 50% 90% Lateral Medial Medial Lateral

33 Prostate Cancer 2 PMH: none PSH: none Family history: no prostate Ca, both parents alive 75 and 83 yrs Erections slightly diminished (not sexually active) No voiding dysfunction

34 Prostate Cancer 2 Bone scan: No mets CT AP WWO contrast: 2.2 x 0.9 left external iliac node 1.6 x 0.7 right external iliac node Prognosis: RRP: 5-year PFP 28% EBRT (+ ADT): 5-year PFP 46% Pathology: ECE: Left 93%, Right 93% SVI: 72% LNI: 56%

35 Prostate Cancer 2 T3a, Gleason 8, PSA 27.6 ng/ml, clinically LN+, M0 Treatment options: Lymph node biopsy Open or laparoscopic radical prostatectomy Neoadjuvant ADT followed by RP EBRT + 6 mos ADT EBRT yrs ADT ADT as primary therapy Enroll in clinical trial neoadjuvant docetaxel + ADT Radical prostatectomy (CALGB - PUNCH) EBRT (RTOG)

36 Prostate Cancer 2 Patient opted for open radical prostatectomy Bilateral nerve resection Pathology: Bilateral established extraprostatic extension Left SVI Gleason 4+3 Negative margins 3 of 18 positive nodes (bilateral) 10-year PFP by nomogram: 12%

37 Prostate Cancer 2 6 weeks postop: PSA 0.11 ng/ml No erections, 1 pad daily for incontinence Treatment options: Immediate EBRT Immediate ADT Immediate chemotherapy and ADT Observation with salvage EBRT at PSA relapse Observation with salvage ADT at PSA relapse (use PSA DT) Observation with salvage ADT at clinical progression

38 Prostate Cancer 2 Elected to follow patient close with plan for deferred ADT based on PSA level and PSA DT PSA history: 05/ / /2007 PSA doubling time: < 3 months months postop: started on ADT (LHRH agonist + AA) Continuous vs. intermittent? Need for bone densitometry? Calcium + vitd3 supplementation? Assess cardiac risk factors? Fasting glucose? Lipid profile?

39 Prostate Cancer 2 Started on intermittent ADT continue if nadir PSA < ADT Start 16 PSA level, ng/ml ADT Start ADT Stop ADT Stop ADT Stop Ser i es Months from Radical Prostatectomy

40 Prostate Cancer-Specific Mortality after Radical Prostatectomy Gleason 8-10 Seminal Vesicle Invasion Lymph Node Metastasis PCSM by Specimen Gleason Score PCSM by Pathologic Stage Stephenson et al. ASCO 2009

41

42 Prostate Cancer 3 53 y.o. healthy male CC: Localized prostate cancer PSA history: 04/ / / / PSA velocity: 3.32 ng/ml/year DRE: Nodule R. mid, T2a Gleason 8, 4/12 cores positive

43 Prostate Cancer 3 Left Right 0/1 1/1+ 0/1 0/1 Base ASAP Glsn 3+4 HG PIN HG PIN 25% Mid 0/1 HG PIN 1/1+ Gleason 8 1/1+ Gleason 8 0/1 HG PIN 10% 50% Apex 1/1+ Gleason 6 0/1 HG PIN 0/1 0/1 10% Lateral Medial Medial Lateral

44 Prostate Cancer 2 PMH: none PSH: none Family history: none Erections Normal (sexually active) No voiding dysfunction

45 Prostate Cancer 3 Bone scan: No mets CT AP WWO contrast: No mets Prognosis: RRP: 10-year PFP 81% EBRT (+ ADT): 5-year PFP 79% Pathology: Organ-confined: 46% ECE: 45% SVI: 30% LNI: 9%

46 Prostate Cancer 3 Standard options discussed for high-risk cancer Erections very important but wants to be cured Treatment options: External-beam radiotherapy +/- ADT Radical prostatectomy Nerve-sparing? Unilateral? Bilateral? Partial vs. complete resection? Decision-making?

47 Cancer Control: Positive Surgical Margins Open RP No. Pts pt2 pt3 Touijer et al % 22% Harris % 48% Smith et al % 60% Han et al % 23% RALRP or LRP* Menon et al % 35% Patel et al % 35% Smith et al % 50% Zorn et al % 48% Touijer et al. 2006* 485 8% 17%

48 Positive Surgical Margins Surgeon is independent predictor of SM+ SM+ risk of PSA recurrence by 2-4 fold Eastham et al. J Urol 2003 Swindle et al. J Urol 2005; Stephenson et al. J Urol 2009 SM+ are frequent indicator for secondary therapy Van der Kwast et al. J Clin Oncol 2008 SM+ may risk of PCSM (HR 1.14, P < 0.001) Stephenson et al. ASCO 2009

49 Side-Specific Risk of Extraprostatic Extension Ohori et al. J Urol 2004;

50 Prostate Cancer 3 Bone scan: No mets CT AP WWO contrast: No mets Prognosis: RRP: 10-year PFP 81% EBRT (+ ADT): 5-year PFP 79% Pathology: ECE: Left 30%, Right 23% SVI: 30% LNI: 9%

51 Prostate Cancer 3 Patient elected to undergo RALRP Bilateral nerve-sparing Pathology: pt2, Gleason 4+3, SM negative, 0/14 LN+ Follow-up: 6 months postop PSA NMA Continent Sexually active with PDE-5 inhibitor

52

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