Thursday, April 23, 2009

Bladder Preservation

MP presents today on Bladder Preservation Therapy:

Presents an 80 yo WM with BPH s/p several local therapies, developed hematuria. Cystoscopy revealed 3 nodulear lesions L posteriolateral bladder. TURBT demonstrated grade 3 transitional cell carcinoma with invasion into the muscularis propria.

T stage:
Ta - non-invasive papillary carcinoma
Tis - carcinoma in situ, "flat tumor"
T1 - invades subepithelial connective tissue
T2 - invades muscle
T2a - invades superficial muscle (inner half)
T2b - invades deep muscle (outer half)
T3 - invades perivesical tissue
T3a - microscopically
T3b - macroscopically (extravesical mass)
T4 - invades other organs
T4a - invades prostate, uterus, vagina
T4b - invades pelvic wall, abdominal wall
N1 - single LN, 2 cm or less
N2 - single LN 2-5 cm; or multiple LN <> 5 cm

Risk Factors: smoking, cytoxan, aromatic compounds, chronic irritation, s. hematobium
95% TCC, 5% SCC in the US

1.Partial Cystectomy
2.Radical Cystectomy
3.Bladder Preservation

Note there is an RCT which is accruing (the SPARE trial) randomizing between cystectomy and bladder preservation.

Partial Cystectomy – Smalden J Urol 2008. T2 and T1 high grade. in 25 selected pts 5yr CSS 84%, 5yr OS 70%. Primarily this is done with dome lesions. Invasion of the trigone is a contraindication.

Initial Work:
Shipley NEJM 1993: 53 pts 40Gy + CDDP, 28/53 with CR, 90% functioning bladder.
University Paris JCO 1993: 54 pts neoadjuvant CTRT, majority had pCR.

Bx proven muscle invasion → TURBT → XRT with CT → reevaluate at around 40-45Gy → if CR continuation of CTRT / if no CR cystectomy.

RTOG trial overview: T2-4 primary, no hydronephrosis

85-12 TURBT, CDDP/RT: CR 67%, 5yr OS 52% 4yr IBS 41%
88-02 TURBT, MCV, CDDP/RT: CR 76% 5yrOS 51% 5yr IBS 36%
89-03 TURBT, +/- MCV, CDDP/RT: CR 59% 5yr OS 49% 5yr IBS 38% (no difference between arms)

MCV – methotrexate, cisplatin, vinblastine

More RTOG:

95-06 TURBT, 5FU+CDDP+RT hypofx to 44Gy (Based on Paris experience): CR 67%, 3yr OS 83%, 3yr IBS 66%
97-06 TURBT, CDDP+BID RT, MCV: CR 74% 3 yr OS 61%, 3yr IBS 48%
99-06 TURBT, paclitaxel+CDDP+BID RT, CDDP/GEM: CR 84% 5yr OS 56%,

total dose 45.6Gy to pelvis, 64.8Gy to bladder tumor.

Rodel JCO 2002: 415 with T2-4 TURBT, CTRT or RT. 72% had CR and were observed. Cystectomy for all recurrences and persistent disease after CTRT. 1980s-2002 f/u 60months. 5yr OS around 50%, with about 40% IBS. 3% late Grade 3 GU toxicity.

R0 resections do better. Pts receiving CDDP did better than no chemo or Carbo.

Shipley Urol 60:2-88, 2002. CR rate 68%, DSS at 5 yrs. 5yr OS around 50%. 2/3 kept bladder. 46% had 5yr DSS.

The current US trial is looking at QD RT + Gem vs BID RT + CDDP/5FU. Also accuring in the UK is the SPARE trial (Cystectomy vs CTRT) and another looking at RT alone vs CTRT (with an additional dose question)

Conclusion: Bladder conservation results in similar 5yr OS of 50-60% compared to cystectomy. Concurrent CDDP based chemotherapy should be used. About 60-70% of patients will have an intact and functional bladder.

Initial fields were 4 field low pelvis (superior aspect at mid SI), to 38.6Gy, then boost tumor bed with 1.5cm margins to 64.8Gy. Weekly CDDP was used (doses 30-40mg/m2).

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