Radiotherapy (RT) Protocol for Prostate Cancer

Radiotherapy (RT) Protocol for Prostate Cancer CGMH-2010-02 *This document is aimed to set up RT protocols for prostate cancer. The treatment guideline for prostate cancer will not be covered here. A. Pre-RT work-up and preparations 1. MRI is recommended for all patients because it is important for staging and treatment choice 1. Staging of primary tumor will base on DRE (for T1-2) and MRI (for T3-4). DRE findings should be described. 2. Pre-treatment PSA level is required for all patients 2 and recommended to be measured by EIA instead of RIA 3. 3. Gleason score should be recorded 4. If pathology report is from other hospital, a review by CGMH is highly recommended. The number of positive piece /total piece for each side should be recorded. involvement in each section should be described. The percentage of positive tumor 4. Bone scan is suggested when either PSA >10, Gleason score > 6 or T2b or above 5. 5. The pre-treatment urination (including night and daytime) and sexual function should be recorded. The urination function should record the number of time needed to wake up for urination and the interval tolerable at the daytime. The sexual function should include (full or partial) erection and penetration. 6. When CT simulation shows that rectum is distended with gas or stuff or the bladder is not distended with water, a repeated CT simulation with good bowel and bladder preparation is necessary 7. Before CT simulation and each treatment, the rectum must be emptied to reduce the anterior displacement for prostate 6. Patients will be educated to take 350 ml water 30 minutes (more water and/or waiting time, if necessary) before treatment or CT simulation. 8. To improve the treatment quality, insertion of fiduical marker and image-guided radiotherapy is strongly recommended 7,8. B. Definitions for RT treatment planning A. CTV for pelvic lymph node (CTVn): the anatomical component of pelvic nodes. The upper margin is higher than the junction of ext. and int. iliac vessels, but not higher than the junction of common iliac vessels. 1

B. CTV for seminal vesicles (CTVsv): visible prostate and SV shown in CT scan. C. CTV for prostate (CTVp): visible prostate and the junction between prostate and SV. D. Rules for creating PTV by expanding each CTV: Since fiducial markers are inserted into prostate and the position and shape of seminal vesicle will change with the distension of bladder and rectum, the margin between CTV and PTV is larger for SV than prostate in patients with fiduical markers. A. PTVn: 0.8 cm expansion in 3 axis from CTVn B. When fiducial marker is inserted for image guidance (PTV with i prefix): i. iptvsv1: 7 mm in dorsal direction and 1 cm for the rest from CTVsv ii. iptvsv2: 7 mm in all directions from CTVsv. iii. iptvp: 5 mm in 3 axis from CTVp C. Without fiduical marker i. PTVsv1: 7 mm expansion in dorsal direction and 1 cm for rest from CTVsv. ii. PTVsv2: 7 mm in ventral-dorsal axis and cranial-caudal axis, 1 cm in left-right axis from CTVsv. iii. PTVp1: 7 mm in dorsal direction and 1cm for rest from CTVsv. iv. PTVp2: 7 mm in ventral-dorsal axis and cranial-caudal axis, 1 cm in left-right axis from CTVsv. C. General principles for radiation dose 9 1. The dose escalation (> 75.6 Gy) will be only given to patients who are inserted with fiduical marker and treated with image-guided RT (IGRT) because these techniques improve the positional precision. 2. The reduction of RT dose is allowed if the dose constraints for rectal and bladder can not meet the safety criteria, especially for patients with multiple co-morbidity or taking anti-coagulant. 3. Radiation dose to primary tumors by external beam: RT dose to prostate: 75.6 Gy without marker and 78.4 Gy with marker, in 42 fractions. RT dose to SV: 50.4 Gy/28 fx for T1-2, 75.6 78.4 for T3. RT dose to pelvic node 10 : 45 Gy (by box) 50.4 Gy (by IMAT). Boost dose to gross LN is allowed. D. Treatment guidelines for prostate cancer 1. Prostate irradiation for patients with evidence of distant metastasis 2

RT to primary tumor is not routinely recommended except for those tumors refractory to hormone therapy and cause clinical symptoms. If RT is given under this condition, it will be considered as long-term palliation and the dose is recommended to be < 72 Gy (usually less than 66.6 Gy); dose will depend on patients disease extension and general condition. 2. Prostate irradiation for patients with evidence of regional nodal metastasis Patients whose disease spread to pelvic lymph nodes, but not to para-aortic LN or other organs are still candidates for curative RT after neo-adjuvant hormone therapy. Following 45 (box field) - 50.4 Gy (RapidArc) to whole pelvis, final dose to prostate/seminal vesicles will be 75.6 Gy if DVH for rectum and bladder tolerance is allowed. Additional boost dose to gross lymph node (by field-in-field or other techniques) will be decided individually. 3. Treatment for localized disease without surgery Low risk group, T1-2a and PSA<10 and Gleason score <7, M0 A. Radiotherapy (RT) 1. Combination of high-dose-rate (HDR) implant plus external radiotherapy (EXRT) 11 HDR implant: 5.5 Gy/per fx., 3 fractions/24 hour with interval between fractions at least 6 hours. EXRT: 50.4 Gy/28 Fx to prostate and seminal vesicle. The PTV is the CTV plus 1 cm margin in all the directions. In the case whose covering index is < 88% or underdose region is not limited in the anterior part, the underdose region will be boosted by the external beam with the IMRT (IMAT) field-in-field technique. The minimal dose to the underdose region will be 110% of the prescribed dose, and the maximal dose is< 120%. 2. EXRT alone: For patients whose condition is not appropriate for surgery or HDR implant, or who chooses EXRT treatment. With marker (Total dose to prostate = 78.4 Gy/42 fx). - Dose prescription and delivery technique: 50.4 Gy/28 fx to prostate and seminal vesicle, and boost with 28 Gy/14 fx to prostate. RT is given by image-guided radiotherapy (IGRT) with either RapidArc 3

radiotherapy technology or Novalis Tx Radiosurgery. - Requirement of dose coverage: 100% dose to CTV, and PTV is treated by 95% of prescribed dose. Maximal dose inside the PTV is < 110% of prescribed dose. The maximal dose to bladder and rectum is less than 105% of prescribed dose. Less than 10 % volume receives > 100% prescribed dose. Less than 25% volume of bladder and rectum receives dose > 70 Gy (90% prescribed dose) 12. Without marker (Total dose to prostate = 75.6 Gy/42 fx) - Dose prescription and delivery technique: 50.4 Gy to prostate and seminal vesicle and 75.6 Gy to prostate by RT to prostate will be given by intensity modulated radiotherapy (IMRT). The dose prescription is - Requirement of dose coverage: 100% CTV is treated by prescribed dose 1.8 Gy, and PTV is treated by 95% of prescribed dose. Maximal dose inside the PTV is < 110% of prescribed dose. The maximal dose to bladder and rectum is less than 105% of prescribed dose. Less than 10 % volume receives > 100% prescribed dose. Less than 25% volume of bladder and rectum receives dose > 72 Gy (95% prescribed dose). Dose will be reduced to 72 Gy (or even lower) if patient s bladder is so small that large volume of bladder is included in the PTV. However, repeated CT simulations and large volume of water intake will be tried to confirm the small bladder volume. Intermediate risk, T1-2, 10 PSA 20 and Gleason score 7, M0 A. RT Neoadjuvant and concurrent total androgen blockade for 4 months, initiated 2 months before RT 13. However, patients might be treated without hormone therapy if there is only one risk factor (10 PSA 20 or GS =7, and no palpable T1). Patients will be treated by either HDR + EXRT or EXRT alone, based on the same criteria as in low risk group. Treatment methods are also same as those in the low risk group except pelvic RT is given for those with risk of pelvic node >=15%. CTVn and PTVn will be No adjuvant hormone therapy is given after RT. 4

For those treated by EXRT alone Risk of pelvic node >=15%, as calculated by Roach s formula: 50.4 Gy/28 fx (for those with marker) or 45 Gy/25 fx (for those without marker) to pelvic node will be given for patients < 75 Y/O old, good performance and no severe co-modality. Risk of pelvic node< 15%: 50.4 Gy to prostate and seminal vesicle and 78.4 Gy/42 fx to prostate by IGRT for those with marker, or 75.6 Gy/42 fx for those without marker. Dose will be reduced to 72 Gy (or even lower) if patient s bladder is small or rectum is highly distended so that large volume of bladder or rectum is included in the PTV. However, repeated CT simulation with good rectal preparation and taking large volume of water to confirm the bladder and rectal volume should be tried. High risk group: T3a, or Gleason score 8, PSA > 20, Very high risk group: T3b-4, but M0 PSA > 20 is considered as high risk group in the literature, however, our experience of high-dose-rate brachytherapy suggested patients had good treatment outcome if they had only one risk factor of 20 < PSA< 80. We assign patients with one risk factor of 20 < PSA< 80 as high risk group, but their treatment follows the protocol of intermediate risk group. Patients who only have one risk factor that GS = 8 can be treated as intermediate risk. A. RT Neoadjuvant hormone therapy by total androgen block, starting 2 months before RT and given during RT, was recommended as a treatment standard. HDR given to T3a patients will be limited to those with < 3 mm extracapsular extension shown in MRI, otherwise patients will be treated by EXRT alone 11. Two-year adjuvant hormone therapy with monthly leuplin will be given 14-16. However, adjuvant hormone therapy may be omitted if patient only have one risk factor of GS = 8. Initial dose of EXRT is 50.4 Gy to prostate and seminal vesicle. For T3b, the dose to P+SV will be 78.4 Gy/42 fx (with marker); SV is 5

excluded from CTV after 50.4 Gy for those <=T3a. 4. RT for patients with biochemical failure or impending biochemical failure after radical prostectomy Patients had PSA levels > 0.2 after radical prostectomy should be defined as biochemical failure 17. If systemic work-up does not detect distant failure, local RT should be considered. Progressive elevation of PSA in three consecutive measurements is also accepted as an indication for local RT, even the PSA is <0.2, However, when the PSA doubling time is less than 4-6 months, distant metastasis is more favored even negative system work-up. Only about 50% patients can get tissue proof for the local relapse. For patients who have no pathological proof of local relapse, 66 Gy cgy/37 fx will be given to the target which includes prostate fossa, posterior bladder wall (1 cm) and anterior rectal wall (7 mm). The treatment is given by IMRT. For patients with pathological proof of relapse in the urethra anastomosis but without visible tumor by MRI, 63 cgy/35 Fx to prostate target (as above) will be given. Further 9 Gy/5 fx will be boosted to urethra site and the final dose is 72 Gy/40 fx. For patients with any visible tumor in the MRI, the dose to the target (as above) is 63 cgy/35 fx and final boost to gross tumor up to 75.6 Gy/42 fx will be given. 5. RT for patients with high risk factors in the pathological specimen after RP Patients who receive radical prostectomy and pathological reports show extracapslar extension, seminal vesicle invasion, or positive margin, are considered to receive post-operative radiotherapy 18. 63 Gy/35 Fx to prostate target (as above) will be given for those with free margin. Dose will be increased to 66.6 Gy to prostate target for those with multiple positive margin, or to urethra anastomosis if only distal positive resection margin. Risk of pelvic node >=15%, as calculated by Roach s formula: If LN dissection is performed and adequate number of LN is reported, pelvic RT is omitted for pathological N0 case. Otherwise, 45 Gy to pelvic node will be given for patients < 75 Y/O old and has good 6

performance and no severe co-modality. E. Follow-up schedule PSA is checked at the day of RT completion. Patients will come back to RTO OPD at 1 month after RT, and then every 3 months. PSA is regularly checked q3 m for 2 years, q4-6 months up to 5 years, and q6 m afterward. However, if elevation of PSA is found, the frequency can be shifted to q 1-2m. Follow-up interval can be prolonged if patient has poor general performance or inconvenience for transportation. Biochemical failure is defined by nadir + 2; the day of failure is defined as at the day of meeting this criterion 19. For patients who are treated with short-term hormone therapy, the PSA will rebound after withdraw of hormone therapy, and the nadir is defined as the nadir after the rebound. The day of failure should be recorded. For those primarily treated with RT and found to have biochemical failure but PSA is <4, systemic work-up usually can not detect metastasis and is not required. MRI is not recommended either for those with negative DRE. Clinical failure is defined as local or distant failure. Local failure is defined when tumor is palpable by DRE and/or MRI shows positive findings. Biopsy is not an absolute indication for diagnosis of local relapse because many patients might refuse biopsy and tissue proof of local failure does not help further management for most of the patients. However, a strong suggestion to patients should be made to patients. F. Schema of RT guidelines 7

Low risk: T1-2a and PSA<10 and Gleason score <7, M0 Intermediate risk: T1-2, 10 PSA 20 and Gleason score 7, M0 T1 with single risk No hormone therapy indicated Short-term hormone therapy Total androgen block, started 2 months before RT, ended with RT HDR brachytherapy: T1-2, or T3a with ECE part < 3mm. 550 cgy x 3 fx in 2 days External beam radiotherapy 75.6 Gy/42 fx H E EXBRT boost by 3D CRT: 50.4 Gy/28 fx to PTVp1 + PTVsv1 EXBRT boost by IMRT (obvious underdose region): 50.4 Gy/28 fx to PTVp1 + PTVsv1 with FIF local b t For both post HDR brachytherapy or EXBRT without IG Pelvic nodal metastatic risk < 15%: 45 Gy/25 fx delievered to PTVn by 3D-CRT Pelvic nodal metastatic risk < 15%: 50.4 Gy/28 fractions delivered to PTVp1 + PTVsv1 by IMRT H EXBRT boost: 5.4 Gy/ 3 fx to PTVp1 + PTVsv1 by E H No further treatment for good brachytherapy plan Local boost to compensate underdose region SV are involved: 12.6 Gy/7 fractions delivered to PTVp1+PTVsv1 followed by 12.6 Gy/7 fractions delivered to PTVp2+PTVsv2. SV are not involved: 12.6 Gy/7 fractions delivered to PTVp1 followed by 12.6 Gy/7 fractions delivered to PTVp2. High risk: T3a, or Gleason score 8, PSA > 20, Very high risk group: T3b-4, but M0 T2 with single risk Long-term hormone therapy 1. Total androgen block, started 2 months before RT, till the end of RT, followed by LHRH analogue injection for 2 years to life-long. or 2. Orchiectomy IGRT with fiducial marker assistance: 78.4 Gy/42 x G Pelvic nodal metastatic risk < 15%: 50.4 Gy/28 fx delivered to iptvsv by IMAT or Novalis Tx Radiosurgery Pelvic nodal metastatic risk 15% or N1:50.4 Gy/25 fx delievered to PTVn by IMAT G SV are not involved: 28 Gy/14 fx delivered to iptvp. SV are involved: 1. iptvp: 28 Gy/14 fx 2. 14 Gy/7 fx to iptvsv1 14Gy/7 fx delivered to 8

This document is the consensus of RT technique for prostate cancer and approved by Yen-Chao Chen, M.D. Kang-Hsing Fan, M.D. Chien-Sheng Tsai, M.D. (also the director of the department in Keelung) Ji-Hong Hong, M.D., Ph.D. (also the director of the department) 9

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