0
Ahmed Zeeneldin
¨   Cancer: An abnormal growth of cells which tend to    proliferate in an uncontrolled way and, in some    cases, to meta...
Anatomy1.   Position2.   5 Lobes:          •     Ant,          •     Post : cancer          •     Median: BPH          •  ...
A: normal                             B: BPHC: intraepitjrlial neoplasia          D: Prostatic Adeno CANB: IHC of p501s   ...
Tumor Grade                                          Gleason’s GradeG1: Well differentiated (slight anaplasia)           2...
Ahmed Zeeneldin   6
¨   The sum of first and    second most common    tumor pattern¨   G pattern of 1st +    G pattern of 2nd                 ...
T1                T2                T3               T4            N1          M1  Clinically       Confined to        Ext...
T1a         T1b,c             T2        T3         T4N0M0              G1: I          II                II        III     ...
¨       Clinically Localized: T1-3a, N0M0        ¡   Low: ALL            ú Very low: as Low + T1a + PSA desity: <0.15 ng/m...
¨   PSA¨   DRE          Ahmed Zeeneldin   11
¨   In 2008:    ¡   25% of Men cancer    ¡   29,000 deaths¨   PSA screening:    ¡   Detect early stage        (asymptomati...
¨   Options    ¡   Active surveillance    ¡   Surgery    ¡   Radiotherapy (RT)    ¡   Systemic therapy¨   Treatment depend...
¨   Possible for groups & challenging for individuals¨   Social Security Administration tables    ¡   http://www.ssa.gov/O...
¨       Clinically Localized: T1-3a, N0M0        ¡   Low: ALL            ú Very low: as Low + T1a + PSA desity: <0.15 ng/m...
¨   Surgery: radical prostatectomy¨   RT: EBRT and Brachytherapy¨   Systemic therapy:    hormonal therapy or chemotherapy ...
¨      Prostate and seminal                  vesicles are removed           ¨      Pelvic LNs can also                  re...
¨   EBRT (3D, IMRT):    ¡ 70-79 GY (8-9 w)    ¡ Localized (LR, IR, HR) &      locally advanced¨   Brachytherapy:    ¡   12...
Surgery        RT                                                Radical       EBRT (3D, IMRT:                            ...
¨   Castration:    ¡ Surgical: orchiectomy    ¡ Medical: LHRH¨   Combined androgen    blockage (AB):    ¡   Castration+ant...
Ahmed Zeeneldin   21
¨   Suppress testosterone levels to castrate level    (< 50 ng/mL)    ¡ With surgical castration this can take few weeks  ...
¨   Combined or triple androgen blockage    provides no proven benefit over castration    alone    ¡   Meta-analysis showe...
¨   Primary for metastatic disease: immediate    therapy¨   With Definitive RT:    ¡   Localized high-risk    ¡   Locally ...
¨       Localized disease (T1-3a, N0M0):        ¡ VLR: LE< 20 Y à active surveillance (PSA q 6m, DRE q 12 m): 2010 update ...
Anthony et al, Cancer.                                             LOCALIZED2002 ;95(2):281-6.                   Risk     ...
Low risk and intermediate risk with low biopsy tumor volume                               Ahmed Zeeneldin                27
intermediate risk with high biopsy tumor volume and high-risk                                Ahmed Zeeneldin              ...
Potters et al, Oncol. 2004;71:29-33.Prospective, T1-T2Primary endpoint: (failure from Biochemical RecurrenceFFBR)Mono-ther...
Ahmed Zeeneldin   30
¨   Survival Following Primary Androgen        Deprivation Therapy Among Men With        Localized Prostate Cancer    ¨   ...
¨   McLeod et al, J Urol. 2006;176:75-80.¨   Standard of care (RT, RP (Adj)) -> then¨   Randomization to bicalutamide 150 ...
Ahmed Zeeneldin   33
¨   Adverse Effects of ADT:    ¡ Osteoporosis, sarcopenia ( - mucsle) & - lean BM      ú Greater incidence of clinical fra...
¨   Options:    ¡   Early ADT: may be better    ¡   Late ADT: acceptable, upon progression¨   Criteria for early ADT    ¡ ...
¨   Messing et al, Lancet Oncol. 2006;7:472-479.¨   Following RP and Pelvic LND¨   +ve LN¨   Immediate vs delayed ADT    ¡...
Ahmed Zeeneldin   37
¨    Life expectancy:        ¡   <5 Y:            ú Not high-risk for mets or hydronephrosis AND asymptomatic:            ...
T1               T2                  T3              T4¨   LE<10y    ¡   Active surveillance             Clinically       ...
¨    Johansson et al, AMA. 2004;291:2713-2719.¨    Prospective, FU 21 years¨    233 patients, T0-T2 NX M0¨    Untreated an...
¨   Bill-Axelson et al, J Natl Cancer Inst. 2008;100:1144-1154.¨   Prospective, RCT, FU 10 years¨   ~700 patients, T0-T2 N...
T1               T2                  T3              T4¨   LE<10y    ¡   Active surveillance             Clinically       ...
Goserlin (3.6 mg       RTOG 8610                                EBRT             EBRT+ 4mADT    SC M)+             (bulky ...
T1               T2                  T3              T4¨   RT + long term ADT    (2-3y)                            Clinica...
¨   Bolla et al, N Engl J Med. 1997 Jul 31;337(5):295-300.¨   Prospective, RCT, FU 7 years¨   ~415patients, locally advanc...
T1                T2               T3               T4¨   long term ADT    alone:                            Clinically   ...
¨   Used in    ¡   Low risk regardless of LE    ¡   Intermediate risk with LE<10y    ¡   Not undifferentiated tumors even ...
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Prostate cancer update 1_2010

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Comprehensive overview of Prostate Cancer: staging, diagnosis, risk stratification and treatment

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Transcript of "Prostate cancer update 1_2010"

  1. 1. Ahmed Zeeneldin
  2. 2. ¨ Cancer: An abnormal growth of cells which tend to proliferate in an uncontrolled way and, in some cases, to metastasize (spread). Ahmed Zeeneldin 2
  3. 3. Anatomy1. Position2. 5 Lobes: • Ant, • Post : cancer • Median: BPH • 2 Laterals Ahmed Zeeneldin 3
  4. 4. A: normal B: BPHC: intraepitjrlial neoplasia D: Prostatic Adeno CANB: IHC of p501s Ahmed Zeeneldin 4
  5. 5. Tumor Grade Gleason’s GradeG1: Well differentiated (slight anaplasia) 2-4G2: Moderately differentiated (moderate anaplasia) 5-6G3: Poorly differentiated (severe anaplasia) 7-8G4: undifferentiated (marked anaplasia) 9-10 Ahmed Zeeneldin 5
  6. 6. Ahmed Zeeneldin 6
  7. 7. ¨ The sum of first and second most common tumor pattern¨ G pattern of 1st + G pattern of 2nd Pattern 1¨ Min: 2 Max: 10 1 2 3 4 5¨ Prognostication, the 1 2 higher the worse 2¨ GS=7: 3+4 > 4+3 3 7 4 7 Pattern 2 5 10 Ahmed Zeeneldin 7
  8. 8. T1 T2 T3 T4 N1 M1 Clinically Confined to Extends Fixed or Regional inapparent prostate through the invades LN (clinical, prostatic adjacent imaging) capsule structures M1a: non-T1A: incidental<=5% of TURP T2A: <=½ of T3A: capsule organs, regional LN one lobe only muscles, bonesT1B: incidental M1B: bone>5% of TURP T2B: >½ of one lobe T3B: seminal M1C: othersT1C: +ve FNA vesicledue to + PSA T2C: both lobes Ahmed Zeeneldin 8
  9. 9. T1a T1b,c T2 T3 T4N0M0 G1: I II II III IV G2-4: IIN1 and /or M1 IV IV IV IV IV Ahmed Zeeneldin 9
  10. 10. ¨ Clinically Localized: T1-3a, N0M0 ¡ Low: ALL ú Very low: as Low + T1a + PSA desity: <0.15 ng/mL/g + Fewer than 3 biopsy cores positive, 50% cancer in each core ¡ intermediate: One* ¡ high-risk: One* ¡ If more than one move to the next higher category¨ Locally advanced : T3b-4, N0M0 ¡ very high-risk¨ Metastatic: any T, N1 and or M1 LOCALIZED Locally Metastatic advanced Risk Low Intermediate High Very high Extremely high N/M N0M0 N0M0 N0M0 N0M0 N1/M1 T 1-2a AND 2b,2c OR 3a OR 3b-4 Gleason’s Score 2-6 AND 7 OR 8-10 OR PSA (ng/mL) <10 AND 10-20 OR >20 OR Ahmed Zeeneldin 10
  11. 11. ¨ PSA¨ DRE Ahmed Zeeneldin 11
  12. 12. ¨ In 2008: ¡ 25% of Men cancer ¡ 29,000 deaths¨ PSA screening: ¡ Detect early stage (asymptomatic, localized) ¡ and low-risk disease Ahmed Zeeneldin 12
  13. 13. ¨ Options ¡ Active surveillance ¡ Surgery ¡ Radiotherapy (RT) ¡ Systemic therapy¨ Treatment depends on: ¡ Life expectancy ¡ Stage ¡ PSA ¡ Gleason’s score Ahmed Zeeneldin 13
  14. 14. ¨ Possible for groups & challenging for individuals¨ Social Security Administration tables ¡ http://www.ssa.gov/OACT/STATS/table4c6.html¨ Adjusted to the health status 66+16 =92 ¡ Best quartile of health - add 50% 66+16+6=98 ¡ Worst quartile of health - subtract 50% 66+16-6=88 ¡ Middle two quartiles of health - no adjustment 66+16 =92¨ LE: < 5y: no treatment unless symptomatic or high-risk¨ LE:<10y no surgery LE>10y: best therapy Ahmed Zeeneldin 14
  15. 15. ¨ Clinically Localized: T1-3a, N0M0 ¡ Low: ALL ú Very low: as Low + T1a + PSA desity: <0.15 ng/mL/g + Fewer than 3 biopsy cores positive, 50% cancer in each core ¡ intermediate: One* ¡ high-risk: One* ¡ If more than one move to the next higher category¨ Locally advanced : T3b-4, N0M0 ¡ very high-risk¨ Metastatic: any T, N1 and or M1 LOCALIZED Locally Metastatic advanced Risk Low Intermediate High Very high Extremely high N/M N0M0 N0M0 N0M0 N0M0 N1/M1 T 1-2a AND 2b,2c OR 3a OR 3b-4 Gleason’s Score 2-6 AND 7 OR 8-10 OR PSA (ng/mL) <10 10-20 >20 Treatment PR or RT RP or RT RT+ ADT RT+ADT ADT+/-RT Ahmed Zeeneldin 15
  16. 16. ¨ Surgery: radical prostatectomy¨ RT: EBRT and Brachytherapy¨ Systemic therapy: hormonal therapy or chemotherapy ¡ Hormonal therapy: ú Orchiectomy, LHRL ú Ani-androgens ú Fenasteride ú Combinations ADT: two or three ¡ Chemotherapy: ú Mitoxantrone & steroids ú paclitaxel Ahmed Zeeneldin 16
  17. 17. ¨ Prostate and seminal vesicles are removed ¨ Pelvic LNs can also removed. ¨ The urethra is joined to the bladder. ¨ Impotence: cavernous N ¨ No ejaculation ¨ Indications: localized LR, IR (T1-T2) with life expectancy > 10yearsAhmed Zeeneldin 17
  18. 18. ¨ EBRT (3D, IMRT): ¡ 70-79 GY (8-9 w) ¡ Localized (LR, IR, HR) & locally advanced¨ Brachytherapy: ¡ 125-145 GY (once) ¡ LLR¨ Combined (EB->BR): ¡ LIR¨ PALLIATIVE RT: ¡ Prostate ¡ bone Ahmed Zeeneldin 18
  19. 19. Surgery RT Radical EBRT (3D, IMRT: prostatectomy 70-80Gy)Bleeding and Possible Notransfusion-related effectsAnesthesia ( myocardial infarction and Possible Nopulmonary embolusurinary incontinence and stricture (Urethera) More Very lowpreservation of erectile function Less MoreCavernous nsRT complications: No YesBladder or bowel symptoms 8-9 weeks courseIndication T2, Any T Life expect> Any Life expect 10ySalvage RT Surgery (difficult) Ahmed Zeeneldin 19
  20. 20. ¨ Castration: ¡ Surgical: orchiectomy ¡ Medical: LHRH¨ Combined androgen blockage (AB): ¡ Castration+antiandrogen¨ Triple AB ¡ Castration+antiandrogen +5aReductase inhibitor¨ NB: LHRH cause initial flare, premedicate with anti-androgen for 7 days Ahmed Zeeneldin 20
  21. 21. Ahmed Zeeneldin 21
  22. 22. ¨ Suppress testosterone levels to castrate level (< 50 ng/mL) ¡ With surgical castration this can take few weeks ¡ With medical castration (LHRH) this takes longer (several weeks) ¡ If this not achieved, we add antiandrogens, estrogens or steroids¨ With LHRH: there is initial surge in FSH and LH by pituitarty (LHRH is agonist/antagonist) leading to surge in testosterone that can lead to tumor flare (clinically (pain, obstruction) and radiologically). This flare can last for a week ¡ To avoid flare use androgen receptor blocker for a week before and few weeks during LHRH (Bicalutamide 150 mg)¨ Rapid fall and undetectable PSA is of good prognosis Ahmed Zeeneldin 22
  23. 23. ¨ Combined or triple androgen blockage provides no proven benefit over castration alone ¡ Meta-analysis showed: ú No OS benefit at 2 years ú 2-3% increase in OS at 5 years ú Combinations are better reserved for resistance¨ Antiandrogen monotherapy appears to be less effective than castration, with the possible exception of patients without overt metastases (M0). Ahmed Zeeneldin 23
  24. 24. ¨ Primary for metastatic disease: immediate therapy¨ With Definitive RT: ¡ Localized high-risk ¡ Locally advanced ¡ Timing: ú Before RT: neo-adjuvant ú During: concomitant ú After: adjuvant¨ Aim: early ADT delays mets and symptoms Ahmed Zeeneldin 24
  25. 25. ¨ Localized disease (T1-3a, N0M0): ¡ VLR: LE< 20 Y à active surveillance (PSA q 6m, DRE q 12 m): 2010 update ¡ LR: RT (EB=BT) or Surgery ¡ IR: RT (+/- ADT NCA x 4-6 months) or Surgery ¡ HR: RT + ADT (Neoadj/conccurrent/adjuvant =NCA) x 2-3 years¨ Locally advanced disease (T3b-T4, N0M0): ¡ RT + ADT (NCA) x 2-3 years ú N=2m C=2m A=rest¨ Metastatic disease (any T, N1/M1): ¡ Local therapy; RT ¡ Systemic therapy: ú hormonal àchemo LOCALIZED Locally Metastatic advanced Risk Low Intermediate High Very high Extremely high N/M N0M0 N0M0 N0M0 N0M0 N1/M1 T 1-2a AND 2b,2c OR 3a OR 3b-4 Gleason’s Score 2-6 AND 7 OR 8-10 OR PSA (ng/mL) <=10 <=20 >20 Treatment PR or RT RP or RT+/-ADT 6m RT+ ADT RT+ADT 2- ADT+/-RT 2-3y 3y Ahmed Zeeneldin 25
  26. 26. Anthony et al, Cancer. LOCALIZED2002 ;95(2):281-6. Risk Low Intermediate HighRetrospective N/M N0M0 N0M0 N0M0 T 1-2a AND 2b,2c OR 3a ORPrimary endpoint: 8-y Gleason’s Score 2-6 AND 7 OR 8-10 ORPSA free survival PSA (ng/mL) <=10 <=20 >20 Surgery (RP) RTN 2254 381Low-Risk 88% 78% (S)Intermediate-Risk e low tumor 79% 65% (S)volumeIntermediate-Risk e high tumor 36% 35% (NS)volumeHigh-Risk 33% 40% (S) Ahmed Zeeneldin 26
  27. 27. Low risk and intermediate risk with low biopsy tumor volume Ahmed Zeeneldin 27
  28. 28. intermediate risk with high biopsy tumor volume and high-risk Ahmed Zeeneldin 28
  29. 29. Potters et al, Oncol. 2004;71:29-33.Prospective, T1-T2Primary endpoint: (failure from Biochemical RecurrenceFFBR)Mono-therapy with no adjuvant ADT Surgery RT Brachytherapy (RP)N 746 340 7337-y FFBR (NS) 79% 77% 74% (NS) Ahmed Zeeneldin 29
  30. 30. Ahmed Zeeneldin 30
  31. 31. ¨ Survival Following Primary Androgen Deprivation Therapy Among Men With Localized Prostate Cancer ¨ Lu-Yao et al, JAMA. 2008;300:173-181. ¨ Age 66 y and T1, T2 ¨ Orchiectomy or LHRH PADT SurvillanceN 7867 11,404ALL: 10-y prostate CA specific survival 80% 83% (NS)ALL: 10-y OS 30% 30% (NS)Poorly differentiated tumors 10-y PCSS 60% 54% (S)Poorly differentiated tumors 10-y OS 17% 15% (NS) Ahmed Zeeneldin 31
  32. 32. ¨ McLeod et al, J Urol. 2006;176:75-80.¨ Standard of care (RT, RP (Adj)) -> then¨ Randomization to bicalutamide 150 mg x 2y vs placebo¨ Localized or locally advanced (adj)¨ N+ not allawed No survillance bicalutamide placebo N 1,647 1,645 HR PFS = 1 (NS) 15% 15% HR OS = 1 (NS) 13% 12% HR PSA progression= 0.84 (S) 32% 38% Ahmed Zeeneldin 32
  33. 33. Ahmed Zeeneldin 33
  34. 34. ¨ Adverse Effects of ADT: ¡ Osteoporosis, sarcopenia ( - mucsle) & - lean BM ú Greater incidence of clinical fractures, ¡ Alterations in lipids (+Chol & TG), Obesity, insulin resistance, ú Greater risk for diabetes (+40%) and cardiovascular disease (coronary +15% and MI + 10%). ¡ Screen, prevent and early treat¨ Side effects are proportional to ADT duration¨ Intermittent ADT ¡ Reduce side effects ¡ Same survival effect ¡ Unproven long term efficacy¨ May be considered for those with stable or undetectable PSA Ahmed Zeeneldin 34
  35. 35. ¨ Options: ¡ Early ADT: may be better ¡ Late ADT: acceptable, upon progression¨ Criteria for early ADT ¡ High PSA >50 ¡ Shorter PSA doubling time (rapid velocity ¡ Long life expectancy) Ahmed Zeeneldin 35
  36. 36. ¨ Messing et al, Lancet Oncol. 2006;7:472-479.¨ Following RP and Pelvic LND¨ +ve LN¨ Immediate vs delayed ADT ¡ LHRH: goserlin or Orchiectomy (patient choice)¨ FU 12 years Early ADT Delayed ADT N 47 51 Improved OS HR = 1.8 (S) 1.8 1 Improved PCSS HR = 4 (S) 4 1 Improved PFS HR = 3 (S) 3 1 Ahmed Zeeneldin 36
  37. 37. Ahmed Zeeneldin 37
  38. 38. ¨ Life expectancy: ¡ <5 Y: ú Not high-risk for mets or hydronephrosis AND asymptomatic: - Observe till symptoms develop ú High-risk for mets or hydronephrosis OR symptomatic: - ADT or - RT ¡ >5Y OR symptomatic: ¡ BS and pelvic CT/MRI: ú T3-4: all cases ú T1-2: if PSA >20 or GS =>8¨ Recurrence risk LOCALIZED Locally Metastatic advanced Risk Low Intermediate High Very high Extremely high N/M N0M0 N0M0 N0M0 N0M0 N1/M1 T 1-2a AND 2b,2c OR 3a OR 3b-4 Gleason’s Score 2-6 AND 7 OR 8-10 OR PSA (ng/mL) 1-2a AND 2b,2c OR 3a OR Ahmed Zeeneldin 38
  39. 39. T1 T2 T3 T4¨ LE<10y ¡ Active surveillance Clinically inapparent Confined to prostate Extends through the Fixed or invades (clinical, prostatic adjacent ¡ RT T1A: incidental imaging) T2A: <=½ of capsule T3A: capsule structures <=5% of TURP one lobe only T1B: incidental T2B: >½ of one organs, LE=>10y >5% of TURP lobe T3B: seminal muscles, bones¨ vesicle T1C: +ve FNA T2C: both lobes ¡ As above + due to + PSA ¡ RP+/- pelvic LND: LOCALIZED Locally advanced ú + SM: observe/RT ú +LN: observe/ADT Risk Low Interm High Very high ediate T 1-2a AND 2b,2c OR 3a OR 3b-4 GS 2-6 AND 7 OR 8-10 OR PSA <10 10-20 >20 Ahmed Zeeneldin 39
  40. 40. ¨ Johansson et al, AMA. 2004;291:2713-2719.¨ Prospective, FU 21 years¨ 233 patients, T0-T2 NX M0¨ Untreated and followed up till progression where orchiectomy or estrogens were given¨ Most cancers had an indolent course during first 10 to 15 years.¨ The mortality rate was significantly higher (approximately 6-fold) after 15 years of follow-up when compared with the first 5 years.¨ These findings would support early radical treatment, notably among patients with an estimated LE>15 years. 0-15y >15Y N 233 49 PFS 45% 35% Prostate cancer specific survival 80% 55% Ahmed Zeeneldin 40
  41. 41. ¨ Bill-Axelson et al, J Natl Cancer Inst. 2008;100:1144-1154.¨ Prospective, RCT, FU 10 years¨ ~700 patients, T0-T2 NX M0 RP WW N 347 348 10 y mortality (due to PC) 137 (47) 156 (68) (NS) 12 y PC mortality (HR = 0.65) 13% 18% (S) 12 y mets (HR = 0.65) 19% 26% (S) Ahmed Zeeneldin 41
  42. 42. T1 T2 T3 T4¨ LE<10y ¡ Active surveillance Clinically inapparent Confined to prostate Extends through the Fixed or invades (clinical, prostatic adjacent ¡ RT +/- short term T1A: incidental imaging) T2A: <=½ of capsule T3A: capsule structures ADT 4-6 m <=5% of TURP one lobe only ú Neoadj T1B: incidental T2B: >½ of one organs, >5% of TURP lobe T3B: seminal muscles, bones vesicle ú Concurrent T1C: +ve FNA T2C: both lobes due to + PSA ú adjuvant ¡ RP+/- pelvic LND: LOCALIZED Locally advanced ú + SM: observe/RT ú +LN: observe/ADT Risk Low Interm ediate High Very high¨ LE=>10y T 1-2a AND 2b,2c OR 3a OR 3b-4 ¡ As above without GS 2-6 AND 7 OR 8-10 OR ¡ Active surveillance PSA <10 10-20 >20 Ahmed Zeeneldin 42
  43. 43. Goserlin (3.6 mg RTOG 8610 EBRT EBRT+ 4mADT SC M)+ (bulky T2-4 [5cm]/ LN + or -) flutamide (250 10 y OS (Median OS) 34% (8y) NS 43% (9y) x3xd PO)1. Clin Oncol. 10y DFS 3% (S) 11% 2008;26:585- 10y D Sp Mortality/mets/BF 36/47/80% (S) 23/35/65% 591. x 2 m before RTOG 9610 EBRT EBRT+ EBRT+ 2m concurrent 3MADT 6MADT2. Lancet Oncol. (locally advanced) 2005 ;6(11):841- 50. HR: LF/BFFS/DFS (S) 1 .56/.7/.65 .42/.58/.56x 2 m before 1m HR: DF/PCSS (S) 1 NS .67/.56 concurrentX 5 m before 1m DFCI EBRT EBRT+ 6M ADT concurrent3. JAMA. Unfavourable localized 2008;299:289- All cause Mortality (HR) (S) 1.8 1 295. Ahmed Zeeneldin 43
  44. 44. T1 T2 T3 T4¨ RT + long term ADT (2-3y) Clinically inapparent Confined to prostate Extends through the Fixed or invades ú Neoadj (clinical, prostatic adjacent imaging) capsule structures T1A: incidental T2A: <=½ of T3A: capsule ú Concurrent <=5% of TURP one lobe only ú adjuvant T1B: incidental T2B: >½ of one organs, >5% of TURP lobe T3B: seminal muscles, bones¨ RT + short term ADT T1C: +ve FNA T2C: both lobes vesicle (4-6m): single HR due to + PSA factor LOCALIZED Locally advanced¨ RP+pelvic LND (if Risk Low Interm High Very high possible): ediate ú + SM: observe/RT T 1-2a AND 2b,2c OR 3a OR 3b-4 ú +LN: observe/ADT GS 2-6 AND 7 OR 8-10 OR PSA <10 10-20 >20 Ahmed Zeeneldin 44
  45. 45. ¨ Bolla et al, N Engl J Med. 1997 Jul 31;337(5):295-300.¨ Prospective, RCT, FU 7 years¨ ~415patients, locally advanced¨ RT vs RT+ Goserlin x 3y starting with RT¨ cyproterone acetate (150 mg acetate (150 mg orally per month of treatment to cyproterone orally per day) during the first inhibit the transient during the first month of treatment to day) rise in testosterone inhibit the transient rise in testosterone EBRT EBRT+2y LHRH 5y OS 79% 62% (S) 5yDFS 85% 48% (s) Ahmed Zeeneldin 45
  46. 46. T1 T2 T3 T4¨ long term ADT alone: Clinically Confined to Extends Fixed or ¡ N1 and M1 inapparent prostate (clinical, through the prostatic invades adjacent¨ RT + short term T1A: incidental imaging) T2A: <=½ of capsule T3A: capsule structures ADT (4-6m) <=5% of TURP one lobe only ¡ N1 only not in M1 T1B: incidental >5% of TURP T2B: >½ of one lobe T3B: seminal organs, muscles, bones ¡ Neoadj T1C: +ve FNA T2C: both lobes vesicle ¡ Concurrent due to + PSA ¡ Adjuvant LOCALIZED Locally Meta¨ RP+pelvic LND (if advanced static possible): ¡ Not in M1 Ris Low Interm High Very high N1/M1 k ediate ¡ + SM: observe/RT T 1-2a 2b,2c 3a 3b-4 ¡ +LN: AND OR OR observe/ADT GS 2-6 7 8-10 AND OR OR PSA <10 10-20 >20 Ahmed Zeeneldin 46
  47. 47. ¨ Used in ¡ Low risk regardless of LE ¡ Intermediate risk with LE<10y ¡ Not undifferentiated tumors even if risk is low or intermediate ¡ Not in high or very high risk or mets¨ Protocol: LOCALIZED ¡ PSA: q 3-6m ¡ DRE: q6-12m Risk Low Interm High ¡ Repeat biopsy q 12 m ediate ¡ Less intense if LE<10y T 1-2a AND 2b,2c OR 3a OR¨ Upon progression: GS 2-6 AND 7 OR 8-10 OR ¡ RT or RP PSA <10 10-20 >20 Ahmed Zeeneldin 47
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