Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control

Table 1 The 5-yr overall survival and complete response rates from the University of Erlangen resulting from changes in therapeutic approach over the years[11-14]

Treatment	Complete response	Overall survival
RT alone	61%	40%
RT + carboplatin	66%	45%
RT + cisplatin	82%	62%
RT + cisplatin + 5-FU	87%	65%

RT: Radiotherapy; 5-FU: 5-fluorouracil.

Table 2 Series of trimodality bladder-sparing treatment for muscle-invasive bladder cancer

Study	No. of patients	A’ phase	CR	B’ phase 6 wk later
RTOG 85-12[17]	42	TURBT, 20 × 2 Gy = 40 Gy + CDDP	66%	12 × 2 = 24 Gy + CDDP
RTOG 88-02[18]	91	TURBT, NACT 2 × MCV, 22 × 1.8 = 39.6 Gy + CDDP	75%	14 × 1.8 = 25.2 Gy + CDDP
RTOG 89-03[8]	123	TURBT, NACT 2 × MCV vs no NACT-22 × 1.8 = 39.6 Gy + CDDP	61% vs 55%	14 × 1.8 = 25.2 Gy + CDDP
RTOG 95-06[19]	34	TURBT, (3 Gy × 2 per day) × 4 = 24 Gy + 5-FU/CDDP	67%	(2.5 Gy × 2 per day) × 4 = 20 Gy + 5-FU/CDDP
RTOG 97-06[20]	47	TURBT, (1.8 Gy + 1.6 Gy per day) × 12 = 40.8 Gy + CDDP	74%	(1.5 × 2 per day) × 8 = 24 Gy + CDDP→ACT 3MCV1
RTOG 99-06[21]	80	(1.6 + 1.5 per day) × 13 d = 40.3 + CDDP/paclitaxel	81%	(1.5 x 2 per day) × 8 = 24 Gy + CDDP/paclitaxel
Housset et al[10]	54	(3 Gy × 2 per day) × 4 = 24 Gy + CDDP/5-FU	74%	(2.5 Gy × 2 per day) × 4 = 20 Gy +CDDP/5-FU)
Given et al[22]	93	NACT 2-3 × MVAC/MCV→36 × 1.8 = 64.8 Gy + CDDP	63%
Fellin et al[23]	56	NACT 2 × MCV→20 × 2 = 40 Gy + CDDP	50%	12 × 2 = 24 Gy + CDDP
Kachnic et al[24]	106	TURBT, NACT 2 × MCV→RCT: 25 × 1.8 = 45 Gy + CDDP	66%	11 × 1.8 = 19.8 Gy + CDDP)
Arias et al[25]	50	TURBT, NACT 2 × MVAC→25 × 1.8 = 45 Gy + CDDP	68%	10 × 2 = 20 Gy
Zapatero et al[26]	40	TURBT, NACT 3 × MCV→30 × 2 = 60 Gy	70%
Chen et al[27]	23	TURBT, 30 × 2 = 60 Gy or 34 × 1.8 Gy = 61.2 Gy + CDDP/FU/leucovorin	89%
Peyromaure et al[28]	43	TURBT, (3 Gy × 2 per day) × 4 = 24 Gy + CDDP/FU	74%	(3 Gy × 2 per day) × 4 = 24 Gy + CDDP/FU
Danesi et al[29]	77	NACT 2 × MCV→(3 × 1 Gy per day) × 23 = 69 Gy or (2 × 1.5 Gy per day) × 23 = 69 Gy	90%
George et al[30]	60	NACT 2 × MVAC/MCV→65 Gy (median dose) + CDDP/carbo/5-FU	75%
Kragelj et al[31]	84	32 × 2 = 64 Gy + concurrent vinblastine	78%
Cobo et al[32]	29	NACT 2 × MCV/GC→25 × 1.8 = 45 Gy + CDDP	86%	4 wk later: RT-alone 11 × 1.8 Gy = 19.8 Gy
Perdonà et al2[33]	43	NACT 2 × MCV→median dose 65 Gy standard fractionation	74.40%
Perdonà et al2[33]	78	NACT 2 × MCV→median dose 65 Gy standard fractionation + CDDP	89.70%
Gamal El-Deen et al[34]	186	None vs NACT 2 × MCV/MVAC/GC→25 × 1.8 = 45 Gy + CDDP	81.60%	11 × 1.8 Gy = 19.8 Gy + the same chemo
Sabaa et al[35]	104	NACT 3 × GC→20 × 2 = 40 Gy + CDDP	78.80%	10 × 2 = 20 Gy + CDDP
Gogna et al[36]	113	32 × 2 = 64 Gy RT + CDDP	70%
Choudhury et al[37]	50	20 × 2.625 = 52.5 weekly Gemcitabine	88%
James et al[15]	71 111 RT/CT arm	20 × 2.75 Gy = 55 Gy + mitomycin C and 5-FU or 32 × 2 Gy = 64 + mitomycin C and 5-FU	80.7%3
Coppin et al[16]	51 RT/CT-arm	30 × 2 Gy = 60 Gy with CDDP	47%
Sauer et al[11]	95	50.4-59.4 Gy at 1.8 Gy plus carboplatin	66%
Rödel et al[12]
Weiss et al[13]
Ott et al[14]
Sauer et al[11]	145	50.4-59.4 Gy at 1.8 Gy plus cisplatin	82%
Rödel et al[12]
Weiss et al[13]
Ott et al[14]
Sauer et al[11]	49	50.4-59.4 Gy at 1.8 Gy plus Cisplatin/5-FU	87%
Rödel et al[12]
Weiss et al[13]
Ott et al[14]

¹Number of fractions in RT or number of cycles in chemotherapy; ²In this study neoadjuvant CT followed by RT was compared to neoadjuvant CT followed by combined RCT (radio-chemotherapy);

³Calculated from Kaplan-Meier curves. CDDP: Cisplatin; 5-FU: 5-fluorouracil; MCV: Methotrexate, cisplatin and vinblastine; GC: Gemcitabine-Cisplatin; CR: Complete response; TURBT: Transurethral resection of bladder tumor; RT: Radiotherapy; CT: Chemotherapy; NACT: Neoadjuvant CT; ACT: Adjuvant CT; RTOG: Radiation therapy oncology group; MVAC: Methotrexate, vinblastine, doxorubicin and cisplatin.

Table 3 Local control rates after external beam radiotherapy-alone for different dose and fractionation schedules

Study	No. of patients	RT fractionation schedule	CR rate
Gospodarowicz et al[38]	254	15 × 2.33 Gy + 5 × 3 Gy	57%
Cowan et al[39]	60	20 × 2.63 Gy = 52.5	75%
Cowan et al[39]	45	16 × 3.44 = 55 Gy	71%
Cowan et al[39]	44	20 × 2.88 = 57.5 Gy	80%
Pos et al[40]	50	20 × 2.75 Gy = 55	74%
Scholten et al[41]	123	6 × 6 = 36 Gy (1 fraction per week)	44%
Shipley et al[7]	58	36 × 1.8 = 65 Gy	56%
De Neve et al[42]	67	33 × 2 = 66 Gy	55%
Yavuz et al[43]	87	(25 × 1.8) + (15 × 1.5 as a second fraction per day the last 3 wk) = 67.5 Gy	64%
Borgaokar et al[44]	163	20 × 2.625 = 52.5 Gy	61%
James et al[15]	71	20 × 2.75 Gy = 55 Gy	69.70%
	106	32 × 2 Gy = 64
Coppin et al[16]	48, RT-alone arm	30 × 2 Gy = 60 Gy	31%
Sauer et al[11]	126	50.4-59.4 Gy at 1.8 Gy	61%
Rödel et al[12]
Weiss et al[13]
Ott et al[14]
Edsmyr et al[45]12	85	32 × 2 = 64 Gy (in 8 wk) 2 wk rest after half of total dose	36%
	83	(3 × 1 Gy per day) × 28 = 84 Gy (in 8 wk) 3 fractions per day, 4 h apart	59%
Gobolenko et al[46]12	43	30 × 2 = 60 Gy, (in 8 wk)	16%
2	26	2 × 1 Gy per day) × 30 = 60 Gy, (in 8 wk)	23%
2	61	(2 × 1 Gy per day) × 35 = 70 Gy (in 9 wk)	34%
2	47	(2 × 1.2 Gy per day) × 28 = 67.2 Gy (in 7.5 wk)	23%

¹In those two randomized studies hyperfractionation was used with a high total dose and resulted in a significantly superior complete response (CR) and survival. However they were not included in our analysis as they were conducted in 70 s and 80 s (see “Methods and Material”);

²The studies below were not included in the present analysis. They are presented to show the advantage of hyperfractionated radiotherapy (RT)-schedules and the higher biologically effective dose delivered.