South East Scotland Cancer Network Prostate Cancer Management Protocol.

Transcription

1 South East Scotland Cancer Network Prostate Cancer Management Protocol. INTRODUCTION Prostate cancer is the second most common cancer in men in Scotland, accounting for 17% of all male cancer registrations. Its incidence has increased by 25% over the last 10 years, mainly as a result of increased PSA testing. Prostate cancer is the 3 rd most common cancer cause of death in males, accounting for 10% of Scottish male cancer deaths. Prognostic Categories 5yr PSA relapse Prognostic Features free survival Good Prognosis: T12 AND PSA 10 AND Gleason 6 85% Intermediate Prognosis: One of the prognostic indicators raised 65% Poor Prognosis: Two of the prognostic indicators raised 35% Scottish Male AllCause Survival Statistics Age Median Life Expectancy (deaths from all causes) years years years years years DIAGNOSIS Prostate Biopsy Protocol To comply with the 62 Day Rule (time from referral to first treatment), all patients should be offered a date for TRUS/prostate biopsies within two/three weeks of referral. Exceptions are those in whom the diagnosis of prostate cancer is unlikely to affect their management ( eg the elderly >75 years and/or other comorbid factors). Where numbers of referrals are such that prioritisations are necessary the following guidance is to be used. PROSTATE BIOPSY FOLLOW UP PATHWAY PROSTATE BIOPSY HIGH GRADE PIN ATYPIA UNCONFIRMED POSITIVE RESULT NEGATIVE BIOPSY REPEAT BIOPSY 2 MONTHS HIGH GRADE PIN ATYPIA UNCONFIRMED UROLOGIST HISTOLOGY CLINIC OR TELEPHONE CALL OR UROLOGIST STAGING MRI, BONE SCAN MDT MEETING REPEAT PSA 6 GP PSA < 10 REPEAT 6 MONTHS GP PSA > 10 REPEAT BIOPSY

2 Five cores from a representative area in each lobe, for example, Lateral, Apex, Base, Middle and Medial. Specimens can be fixed in blocks of 5 with reference to an agreed sequence or fixed separately. Pathology Report to include number, site (right or left), % core involved, Gleason and presence of microinvasion. Appointment Protocol: Patient information leaflets on PSA and prostate biopsies. Letter of appointment. Offer of counselling with nurse specialist. Histology to GP and urologist.. MDT MEETING AND STAGING. Issues to be discussed/reviewed: Fitness and Comorbidities. Symptoms (including LUTS Lower Urinary Tract Symptoms). T stage and Prostate volume. PSA (post retention/uti if relevant). Gleason. No. + % of cores involved. Bone Scan/CT/MRI workstation access preferable. Investigations: All patients: FBC, U+E, Creatinine, Alk. Phos. PSA. Staging Scans: Most will have had their scans before the meeting. The following guidance may be helpful for patients considered suitable for radical therapy PSA 10 OR GS 7 to undergo staging Bone Scan and CT/MRI abdomen + pelvis. T1c GS 6 and 50% of total biopsy core length is involved by cancer, consider MRI (since higher risk of extracapsular spread which would influence against Surgery/Brachytherapy). Urine flow studies and Residual urine volume esp. if Brachytherapy considered. Cystoscopy + EUA, IVU in selected cases. Consider MRI to support watchful waiting approach in selected patients. Scans may not be required if their result will not influence management. TNM Staging: TNM stage UICC 2002 classification (6 th edition). MANAGEMENT. Localised Disease Treatment Options. Watchful Waiting: Androgen Ablation: 2 groups of patients: 1) Good prognostic group who may be young/fit with low PSA/T stage/gs for whom the benefits of early radical therapy are unclear. 2) Older/less fit patient group with any prognostic features who are considered unlikely to require treatment within predicted lifetime or 10 years (or 5 years if GS 810). Active DRE/PSA/Symptom monitoring in clinic with intervention if symptoms/psa doubling time /target PSA reached. 2 groups of patients: 1) Patients at very high risk of occult metastatic disease PSA >20/GS810/T34 who are likely to be incurable and in whom the benefits of local radical therapies are unclear. 2) More elderly patients (+/ significant comorbidities) with organconfined disease who are potentially curable but who are not considered fit for local radical therapies. 3monthly LHRHa (e.g. Zoladex 10.8mg s.c.) with initial 3 weeks of antiandrogen cover (e.g. Casodex 50mg o.d.).

3 Associated toxicities: flushing/sweats, weight gain, fatigue, gynaecomastia, impotence, lack of libido, depression, bone demineralisation. Surgery: Radical Prostatectomy. In selected cases: nerve sparing, pelvic lymphadenectomy. Treatment option if: Fit for anaesthetic, PSA<20, Any GS, T stage <T3, seminal vesicles uninvolved, no extracapsular extension, severe LUTS (treats symptoms as well). Associated toxicities: Incontinence 3%, impotence 80%. Brachytherapy: External Beam: Radiotherapy Radioactive Iodine 121 seeds to whole prostate under USS guidance. Prescribed Dose 145Gy to prostate + 3mm margin around lateral borders and +1 mm posteriorly. 99.5% of volume to receive 145Gy, 6070% of prostate volume to receive 150%=217.5Gy, <25% of prostate to receive 200%=290Gy, Urethra to receive 150%=217.5Gy, Rectum to receive 100%=145Gy and 2cm 3 to receive 100Gy. Option if T12a (and small volume pt2b), prostate volume 50cc (consider 3 months LHRHa if larger), flow rate 10mls/second and low residual bladder volume (<150mls), International Prostate Symptom (IPSS) <20 with minimal obstructive symptoms, no prev. TURP, GS 6/PSA 20 OR GS 7/PSA 15 OR GS 810/PSA 10. High number/% of prostate biopsy cores involved is a relative contraindication. Pubic arch interference may be identified at volume study. Associated toxicities: Urethritis peak 3/12, most settled 6/12, occasional patients at 1 yr. Acute urinary retention 8%. Urethral stricture ~10% developing from 12 months onwards. Significant proctitis <10% improving over 1 year 2% persisting symptoms. Up to 20% pr bleeding persisting up to 4 years. Impotence despite medical therapy up to 50%. Decreased semen volume. Incontinence few patients incontinent at 1 year. T13,N0M0. All patients to receive 3 months neoadjuvant LHRHa (e.g. monthly Zoladex 3.6mg with initial antiandrogen cover). 3 or 4 field, CT planned conformal radiotherapy to prostate. 15MeV. PTV encompasses prostate with 1cm margins superoinferiorly and anterolaterally, 0.6cm margin posteriorly. 5500cGy in 20 fractions over 4 weeks (or equivalent) to isocentre. Dose limits: Rectum: <3% to receive 100% of dose to isocentre (=5500cGy). <25% to receive 95%. <30% to receive 90%. <50% to receive 75%. Bladder: <25% to receive 100% of dose to isocentre. <50% to receive 90% of dose to isocentre. Neoadjuvant Androgen Ablation. Femoral Heads: 2cm 3 to receive <70% of dose to isocentre. Include seminal vesicles if T2b, MRI involvement or T12a and [PSA+((GS6) x10)] 15%. Consider pelvic nodal irradiation if Partin risk [2/3PSA+((GS6) x10)] =1530%. Associated toxicities: Worsening acute cystitis in ~80%, acute proctitis in ~80%. Late severe bladder/bowel damage in 3%, impotence ~60%. Late rectal bleeding ( G2) ~30%. EBXRT: Minimum of 3 months LHRHa (with initial 3 weeks antiandrogen cover) for all patients treated with EBXRT reduces prostate volume by 2550% and decreases late toxicity. Possible survival advantage for selected patients (GS26 in RTOG 9413). Brachytherapy: May be used in selected patients considered otherwise suitable for brachytherapy who present with prostate volumes 5070mls. Surgery: Not used preprostatectomy reduces pathological positive margin rate but not outcome measures. Adjuvant Androgen Ablation. Following EBXRT survival advantage for GS810 patients (RTOG 8531). 3 monthly LHRHa (with initial 3 weeks antiandrogen cover) for 2 years. [Consider for GS7 patients considered at high risk e.g. T3, high PSA)]. Significant side effects of flushing, sweating, impotence, arthralgia, myalgia, oedema, weight gain, sleep and mood disturbance. Following Prostatectomy consider for poor risk patients.

4 Management Influences in Localised Disease. Severe Lower Urinary Tract Symptoms Prostatectomy or TURP EBXRT. T stage Prostatectomy and Brachytherapy contraindicated if T3. Gleason GS 810 more likely to be associated with extracapsular spread/seminal vesicle involvement and node positivity. PSA PSA more likely to be associated with extracapsular spread/seminal vesicle involvement and node positivity. [For predictions of local disease extent derived from AJCC T Stage/Gleason /PSA see Partin tables and calculator at Surgical fitness. Age/Concurrent disease Increased age and significant comorbidities increases likelihood of death from other causes before prostate cancer influences quality of life. Thus Watchful Waiting or Androgen Ablation alone are suitable treatment approaches. MRI findings Extracapsular spread or seminal vesicle involvement influence against Prostatectomy and Brachytherapy. Prostate volume preferred 50mls for Brachytherapy. Radical Salvage Therapies. Surgery failure EBXRT. For patients a) in whom PSA fails to fall to <0.1ng/ml, in whom MRI and bone scan show no evidence of metastases, b) in whom PSA falls to <0.1ng/ml and then rises slowly (doubling time >6 months) with negative staging. Treatment should be instituted before PSA rises above 1.5ng/ml. Technique and dose/fractionation schedule: 3 field, CT planned conformal radiotherapy to prostate. 15MeV. PTV = Prostate bed and surgical clips with 2cm margin in all directions. 5000cGy in 20 fractions over 4 weeks (or equivalent) to isocentre for microscopic disease (up to 5500cGy (or equivalent) if macroscopic disease). EBXRT failure Cryotherapy* / Surgery. Brachytherapy failure Cryotherapy / Surgery. * Mr Damien Green. Department of Urology, City Hospital NHS Trust, Kayll Road, Sunderland, SR4 7TP. Patients require prostate volume <50cm 3, biopsy proven recurrence, negative restaging MRI/IBS, three consecutive rises in PSA, fit for general/spinal anaesthetic. Usually discharged next day with suprapubic catheter in situ 1014 days. Metastatic Disease. Androgen Ablation: 1 st line LHRHa e.g. Zoladex 10.8mg 3 monthly subcut injection. 2 nd line Add antiandrogen (Maximal Androgen Blockade MAB) e.g. Casodex 50mg daily. 3rd line Stilboestrol 1mg od. + Aspirin 75mg od. 4 th line Prednisolone 5mg bd. [Selected patients may be started on Maximum Androgen Blockade (MAB) LHRHa + antiandrogen. Chemotherapy: Consider for fit patients who fail 2 nd or 3 rd line androgen ablation therapy. 1 st line: Docetaxel 75mg/m 2, 3 weekly + Prednisolone 5mg bd (awaiting decision of appeal to Scottish Medicines Consortium). Palliative Radiotherapy: 800cGy single fraction to 3000cGy in 10 fractions depending upon field size/site. Hemibody irradiation 600cGy (to MPD) upper hemibody. 800cGy (to MPD) lower hemibody. Bisphosphonates currently available on namedpatient basis. Palliative care services. Strontium MBq. Pure βemitter. Physical half life 50.5 days MeV. Max range in tissue 8mm. Excretion: ⅔ renal, ⅓ faecal. Time to analgesia 720 days. Warnings: Causes bone marrow suppression, esp WBC/Platelets ensure FBC checked before administration (caution if WBC < 2.4, Platelets <100). Care in renal failure. May require catheterisation if urinary incontinence. Contraindicated if short life expectancy.

5 OUTCOME STATISTICS. 5 and 10year PSA relapse, Disease Specific Survival, Overall Survival and toxicity results (+ outcomes specific to procedure e.g. brachytherapy d90, surgery positive margin rates) should be audited every five years. Longterm strategy should be the development of continuous outcomes database. ONGOING CLINICAL TRIALS. ProtecT: Study investigating management of early prostate cancer. PSA screening with prostatectomy vs conformal external beam radiotherapy vs active monitoring. STAMPEDE: For newly diagnosed patients with highrisk prostate cancer OR PSA relapsing after previous radical local therapy. Androgen suppression (AS) according to local practice vs AS+Zoledronic Acid vs AS + Docetaxel vs AS + Colecoxib. Exclusion criteria: Prior prolonged systemic therapy, CNS mets, peripheral neuropathy, surgery in last 4 weeks, Creatinine clearance <30 mls/min, Cox2inhibitor <6 months prior to trial entry, IHD/CVA. TRAPEZE: For patients with hormonerefractory prostate cancer (failing LHRHa/Antiandrogen) + bone mets. Docetaxel/Prednisolone vs Docetaxel/Prednisolone/Zoledronic Acid vs Docetaxel/Prednisolone/Strontium 89 vs Docetaxel/Prednisolone/Zoledronic Acid/Strontium 89. Exclusion criteria: Prior chemotherapy, prior XRT to >25% of bone marrow or pelvis, prior Strontium therapy, CNS mets, peripheral neuropathy.

6 PARTIN TABLES (1997 results and 2001 update). Figures represent % of patients with described pathologic stage. Gleason Gleason (8495) 9 (415) 0 (02) 0 (01) 82(7390) 17(926) 1 (03) 0 (02) 78(6888) 19(1129) 1 (03) 1 (07) 2001 PSA ng/ml / 1997 PSA T1a T1b T1c T2a T2b T2c T3a 80(7286) 95(8999) 91(7998) 88(7397) 86(7197) 19(1326) 5 (111) 9 (221) 12(327) 14(399) 1 (03 0 (01) 84(7582) 14(73) 1 (04) 0 (02) 66(5773) 32(2440) 2 (04) 1 (02) 61(5269) 35(2743) 2 (04) 2 (15) 43(3453) 44(3554) 6 (113) 6 (213) 31(2043) 34(2744) 9 (516) 4 (27) 90(8893) 9 (712) 0 (01) 79(8485) 17(1325) 2 (15) 1 (02) 71(6279) 25(1834) 2 (15) 1 (04) 66(5476) 28(2038) 4 (110) 1 (04) 81(7785) 17(1321) 1 (02) 0 (01) 64(5671) 29(2336) 5 (19) 2 (0*5) 53(4363) 40(3049) 4 (19) 3 08() 47(3559) 42(3253) 7 (216) 3 (09) 75(6981) 22(1728) 2 (03) 1 (02) 54(4663) 35(2843) 6 (212) 4 (010) 43(3354) 45(3556) 5 (111) 6 (014) 37(2649) 46(3558) 9 (220) 6 (016) 75(6381) 24(1733) 1 (04) 1 (04) 51(3863) 36(2648) 5 (113) 6 (018) 39(2654) 45(3259) 5 (112) 9 (026) 34(2148) 47(3361) 8 (219) 10(027) 40(2653) 51(3865) 7 (314) 2 (04) 35(2248) 53(4165) 7 (413) 5 (29) 19(1129) 52(4063) 19(1031) 9 (417) 2001 PSA ng/ml / ng/ml T1a T1b T1c T2a T2b T2c T3a 70(6079) 92(8298) 85(6996) 80(6195) 78(5894) 43(2758) 27(1837) 8 (218) 15(431) 20(539) 22(642) 44(3059) 2 (06) 10(323) 1 (03) 1 (05) 72(6085) 25(1436) 2 (05) 1 (05) 67(5582) 27(1539) 2 (06) 3 (015) 49(3468) 36(2051) 6 (019) 8 (032) 35(1862) 34(1758) 10(034) 18(055) 53(4463) 42(3251) 3 (17) 2 (15) 47(3857) 44(3553) 3 (16) 5 (211) 29(2138) 48(3860) 9 (218) 12(523) 18(1128) 42(2857) 15(429) 23(1043) 84(8186) 15(1318) 1 (01) 68(6274) 27(2233) 4 (27) 1 (02) 58(4867) 37(2946) 4(17) 1(03) 52(4163) 40(3150) 6 (312) 1 (04) 71(6675) 27(2331) 2 (13) 0 (01) 50(4357) 41(3548) 7 (312) 2 (04) 39(3048) 52(4361) 6(212) 2(06) 33(2444) 53(4463) 10(418) 3 (08) 63(5769) 34(2840) 2 (14) 1 (02) 41(3348) 47(4055) 9 (415) 3 (08) 30(3339) 57(4767) 7 (314) 4 (012) 25(1734) 57(4668) 12(522) 5 (014) 61(5070) 36(2745) 2 (15) 1 (04) 38(2750) 48(3759) 8 (217) 5 (015) 27(1840) 57(4470) 6 (216) 7 (021) 23(1434) 57(4470) 10(322) 8 (022) 27(1739) 57(4668) 12(620) 3 (17) 23(1434) 57(4767) 11(618) 9 (515) 11(617) 48(3758) 26(1736) 15(823) 6 (310) 34(2446) 35(2348) 24(1338)

7 Gleason PSA ng/ml T1c T2a T2b T2c 90(78898) 10(222) 80(7883) 19(621) 1 (01) 0 (01) 63(5868) 32(2736) 3 (25) 2 (13) 52(4360) 42(3550) 3 (16) 3 (15) 46(3656) 45(3654) 5 (39) 3 (16) 81(6395) 19(537) 66(6270) 32(2836) 1 (12) 1 (02() 44(3950) 46(4052) 5 (38) 4 (27) 33(2541) 56(4864) 5 (28) 6 (311) 28(2037) 58(4966) 8 (413) 6 (212) 75(5593) 25(745) 57(5263) 39(3344) 2 (13) 2 (13) 35(2940) 51(4457) 4 (411) 7 (415) 25(1852) 60(5068) 5 (39) 10(518) 21(1429) 59(4969) 9 (416) 10(420) 75(5293) 27(748) 55(4464) 40(3280) 2 (14) 3 (17) 31(2541) 50(4060) 6(211) 12(525) 21(1431) 57(4368) 4 (110) 16(632) 18(1128) 57(4370) 7 (215) 16(633) Gleason PSA ng/ml T1c T2a T2b T2c 87(7397) 13B327 75(7277) 25(2125) 2 (23) 0 (01) 54(4959) 35(3240) 8 (61) 2 (23) 43(3551) 47(4054) 8 (412) 2 (14) 37(2846) 48(3957) 13(819) 3 (15) 76(5694) 24(644) 58(5461) 37(3441) 4 (35) 1 (02) 35(3040) 49(4354) 13(918) 3 (26) 25(1932) 58(5166) 11(617) 5 (28) 21(1528) 57(4865) 17(1126) 5 (210) 69(4791) 31(953) 49(4354) 44(3949) 5 (38) 2 (13) 26(2231) 52(4658) 16(1022) 6 (410) 16(5268) 60(720) 8 (514) 9 (613) 15(1021) 57(4867) 19(1129) 8 (416) 67(4591) 33(955) 46(3656) 49(3755) 5 (29) 3 (16) 24(1732) () 13(625) 10(518) 16(1024) 58(4669) 11(421) 13(625) 13(820) 56(4369) 16(526) 6 (310)

8 Gleason PSA OVER 10 / 1997 PSA ng/ml T1a T1b T1c T2a T2b T2c T3a 61(4778) 80(6195) 65(4389) 57(3586) 54(3285) 33(1847) 20(539) 35(1157) 43(1465) 46(1568) 3 (09) 3 (014) 76(6588) 20(1032) 2 (07) 0 (07) 61(4778) 33(1847) 3 (09) 3 (014) 33(1957) 38(1861) 8 (028) 18(057) 40(3150) 50(3959) 5 (110) 5 (211) 33(2542) 49(3859) 4 (18) 13(624) 17(1124) 46(3460) 11(322) 24(1041) 9 (516) 33(2151) 15(432) 40(1960) 62(5864) 33(3036) 4 (3.5) 2 (1.3) 37(3242) 43(3848) 12(917) 8 (511) 27(2134) 51(4459) 11(617) 10(517) 22(1630) 50(4259) 17(1025) 11(518) 42(3846) 47(4352) 6 (48) 4 (37) 20(1724) 49(4355) 16(1122) 14(921) 14(1018) 55(4664) 13(720) 18(1027) 11(715) 52(4162) 19(1229) 17(929) 33(2838) 52(4656) 8 (511) 8 (512) 14(1117) 48(4053) 17(1224) 22(1530) 9 (613) 50(4060) 13(821) 27(1639) 7 (410) 46(3659) 19(1229) 27(1440) 30(2138) 51(4260) 6 (212) 13(622) 11(717) 42(3055) 13(6.24) 33(1849) () 43(2959) 10(320) 38(2058) 6 (310) 41(2757) 15(528) 38(2059) 18(1027) 59(4769) 15(825) 7 (315) 14(822) 54(4464) 14(821) 18(1027) 6 (310) 40(3050) 28(1839) 26(1638) 3 (15) 26(1737) 34(2147) 37(2452) Gleason PSA > 20.0 ng/ml T1a T1b T1c T2a T2b T2c T3a 38(2652) 58(4668) 41(3152) 29(2040) 47(3361) 34(2444) 48(3656) 52(3965) 9 (122) 7 (215) 10(320) 14(429) 4 (017) 1 (04) 1(05) 3(011) 23(1532) 57(4468) 10(221) 10(321) 17(1125) 51(3764) 8 (217) 23(1040) 3 (27) 24(1342) 20(643) 51(2572) 40(3249) 48(4056) 9 (514) 3 (16) 35(2742) 49(4356) 8 (612) 7 (411) 18(1323) 46(3954) 22(1528) 14(921) 10(616) 34(2745) 31(2142) 24(1536) 26(1933) 60(5268) 11(617) 3 (17) 22(1627) 60(5366) 10(715) 8 (513) 10(714) 51(4458) 24(1732) 14(922) 5 (39) 37(2848) 33(2245) 24(1535) 17(1222) 61(5369) 15(923) 7 (313) 13(1017) 57(5064) 13(919) 16(1123) 5 (48) 43(3550) 27(2034) 25(1833) 3 (24) 28(2037) 33(2445) 36(2548) 19(1426) 55(4664) 19(1128) 7 (313) 15(1120) 51(4359) 17(1124) 17(1125) 6 (49) 37(2945) 32(2442) 25(1634) 3 (25) 23(1631) 38(2651) 35(2348) 8 (414) 54(4067) 26(1441) 11(422) 6(310) 46(3458) 21(1333) 26(1638) 2 (14) 29(1940) 36(2549) 32(2045) 1(02) 17(1126) 40(2555) 42(2758) NB Based on AJCC/TNM 2002 (6 th edition) staging. Tables and calculator available online at or