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Controversies in Prostate Cancer. Radiation Therapy. Curtiland Deville, MD Assistant Professor . April 24, 2013 Lancaster General Health CME. Disclosures. None. Outline . Objective: to review current controversies and hot topics in prostate RT: Background Conformality 3DCRT vs. IMRT

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Controversies in prostate cancer

Controversies in Prostate Cancer

Radiation Therapy

Curtiland Deville, MD

Assistant Professor

April 24, 2013

Lancaster General Health CME


  • Objective: to review current controversies and hot topics in prostate RT:

    • Background

    • Conformality

      • 3DCRT vs. IMRT

    • Motion management (IGRT)

    • Dose escalation

      • Hypofractionation

      • SBRT

    • Modality

      • Proton vs. IMRT


  • Controversies and Hot Topics in Prostate RT (not covered):

    • Erectile dysfunction prophylaxis using a PDE-5 inhibitor

    • Brachytherapy:

      • Role in high risk prostate cancer

      • Benefit of androgen deprivation (ADT)

    • Post-prostatectomy RT

      • Adjuvant vs. early salvage

    • Clinically node positive (N1M0)

      • Benefit of definitive RT with ADT

    • Intermediate risk prostate cancer

      • Benefit of short-term ADT in the setting of dose escalation

    • High risk prostate cancer

      • Benefit of elective pelvic nodal irradiation

      • Duration of long-term ADT (are 28-36 months needed)


  • The role of radiotherapy across all risk groups as curative management for prostate cancer is well-established.

2d rt

Evolution of conformality



Rapid Arc

Imrt vs 3d crt

  • No randomized trials comparing IMRT with 3D-CRT for localized prostate cancer.

  • Retrospective data suggest an improved toxicity profile.

    • Medicare Surveillance, Epidemiology, and End Results (SEER) analysis of 12,000 men.

      • IMRT less GI “morbidity,” hip fractures, and additional cancer therapy

        Sheets NC, et al, JAMA 2012

    • MSKCC series of 1571 men

      • IMRT 81 Gy vs. 3D-CRT at lower doses (358 at ≤70.2 Gy and 472 at 75.6 Gy).

      • IMRT significantly reduced grade ≥2 GI toxicity at 10 years (5% vs. 13% 3D-CRT).

        Zelefsky M, et al, Red Journal 2008

Motion management
Motion Management

  • Interfraction Motion

    • Changes in position between fraction, “day to day”

    • External: set-up error

    • Internal: Mostly due to daily changes in rectal and bladder volume

    • Image-guided radiotherapy (IGRT) - daily imaging to provide prostate localization to account variable motion

  • Intrafraction Motion

    • Changes in position while the treatment beam is on, “second by second”

Motion management pre igrt era
Motion Management (pre-IGRT era)

  • Rectal size at RT planning prognostic for PSA-free survival

de Crevoisier, Red Journal 2005

Motion management1
Motion Management

  • Daily localization IGRT techniques to account for interfraction motion:

    • intraprostatic fiducial markers with daily imaging

    • transabdominal US

    • daily in-room CT imaging

    • endorectal balloon immobilization

  • All of these methods employ daily imaging of the prostate in the treatment room.

Motion management2
Motion Management

In this technique, the isocenter is shifted until the bony contours (setup error) or the implanted markers are in agreement (total error).

Graf, RO Journal 2009

reference (simulation film) online (port film) co-registered (right)

Motion management3
Motion Management

  • Cone beam computerized tomography (CBCT) allows volumetric visualization of the prostate and adjacent organs.

    • Daily online correction allows for PTV margins:

      • 4 mm in all directions and 3 mm posterior (Pawlowski, Red Journal 2010)

      • 5 mm all around and 3 mm posterior (Hammoud, Red Journal 2008)

2 stages of image registration: Top: pelvic bone region of interest

Bottom: prostate/sv represented by masked area.

Motion management4
Motion Management

  • Intrafraction Motion

    • Changes in position while the treatment beam is on (“second by second”)

    • Mostly from peristalsis/gas, pelvic floor movement, respiration coughing, etc.

    • Techniques to account for intrafraction motion:

      • RGRT (radiofrequency-guided RT techniques)

      • Rectal balloon

      • Bowel prep (anti-gas tablets and daily bm)

      • Consistent Bladder filling

Motion management5
Motion management

  • Electromagnetic transponders

  • Benefits:

    • localize the prostate similar to fiducial markers but without additional radiation dose

    • real-time tracking, allowing for immediate intervention if prostate moves outside the radiation field.

  • Limitations:

    • Subsequent difficulty of prostate post-treatment follow-up with MRI

    • Patient factors: pacemakers, obese/abdominal girth.

Motion management6
Motion management

  • Endorectal balloon

    • Used for prostate immobilization/fixation

    • Ensures reproducibility of rectal filling and spares posterior rectum

      Teh, Red Journal 2001

78 Gy IMRT plans without (left) and with balloon (right)

Contours: rectal wall (green), anal wall (purple) and PTV (blue).

Dose escalation
Dose escalation

  • Biologic models support dose escalation beyond 80 Gy

  • Improved conformality and IGRT techniques have allowed for dose escalation

  • Multiple randomized trials show improved control rates:

    • MD Anderson: 8-yr freedom from biochemical or clinical failure improved significantly with dose escalation from 70 to 78 Gy (59% vs. 78%).

      Kuban, Red Journal 2008

    • Proton Radiation Oncology Group (PROG) 95-09 collaborative trial compared 70.2 GyE to 79.2 GyE using proton beam after standard photon 50.4/28, finding significantly improved 10-year biochemical PFS.

      Zietman, JCO 2010


  • Shorter courses of RT using larger treatment fractions

    • 2.5 - 3.1 Gy per fraction, rather than standard 1.8 - 2.0 Gy

  • Method of dose escalation

  • Preliminary reports suggest similar outcomes and favorable toxicity profiles:

    • Fox Chase

    • Cleveland Clinic

    • Italian NCI


  • Italian NCI randomized trial

    • 168 men with high-risk prostate cancer.

    • 3DCRT + 9 mo ADT

    • 80 Gy/40 vs. 62 Gy/20 fractions

    • Median f/u 70 months

    • No differences in biochemical, local, or distant failure (right).

    • No differences in toxicity.

      Arcangeli, Red Journal 2010, 2012


  • Multiple multi-institutional randomized trials are ongoing:

    • RTOG 0415 NCT00331773

      • Patients: cT1-T2c, PSA <10

      • Arms: 73.8/41 vs. 70/28

      • Closed: 12/2009

    • Ontario Clinical Oncology Group NCT00304759

      • Patients: Intermediate risk PCA

      • Arms: 78/39 vs. 60/20

      • Target: 1204 patients, completion by 6/2013

    • UK NCT00392535

      • Patients: cT1b-T3a, PSA <= 30, risk of SV+ <30%

      • Arms: 37 fxs vs. 20 fxs vs. 19 fxs

      • Target: 2163 men, completion by 9/2012

  • Long-term results are required before hypofractionation can be considered a standard alternative

Hypofractionation at penn medicine
Hypofractionation (at Penn Medicine)

  • Mild Hypofractionation With Proton Therapy or Intensity Modulated Radiation Therapy (IMRT) for Intermediate-Risk Prostate Cancer

  • 70 Gy/ 28 fractions (2.5 Gy per fractions)

  • currently recruiting

  • Abramson Cancer Center of the University of Pennsylvania

  • Identifier: NCT01352429

  • Eligibility:

    • Clinical stages T1a-T2c N0 M0

    • Gleason score must be in the range 2-7

    • PSA values < 20 ng/ml within 90 days prior to registration.

  • Androgen deprivation at discretion of the treating radiation oncologist.

Stereotactic body radiotherapy sbrt
Stereotactic Body Radiotherapy (SBRT)

  • Extreme hypofractionation

  • Entire dose is administered in a very limited number (~5) of fractions.

  • Requires high degree of precision in defining the target and administering the radiation

    • Immobilization

    • Imaging

    • Motion management


  • Longer follow-up in larger numbers of patients is required to establish the safety and efficacy of this approach

  • Presently SBRT should be performed within the context of a clinical trial

Proton therapy
Proton Therapy

  • Theoretical advantage is its dose distribution.

  • The physical characteristics of the proton beam result in the majority of the energy being deposited at the end of a linear track, “Bragg peak”

  • Dose then falls rapidly to zero beyond the Bragg peak.

Proton therapy vs imrt1
Proton Therapy vs. IMRT

  • Dosimetric study:

  • 10 IMRT vs.10 proton beam to 78 Gy

  • Mean rectal dose-volume histograms

    Vargas et al. IJROBP 2007

Proton therapy vs imrt2
Proton Therapy vs. IMRT

  • No randomized trials comparing proton therapy to photon therapy or brachytherapy in men with clinically localized prostate cancer.

  • Retrospective analyses have not established whether proton beam therapy (either alone or in combination with photon therapy) is less toxic than photon therapy alone or brachytherapy

Proton therapy vs imrt retrospective
Proton Therapy vs. IMRT (retrospective)

  • Medicare-SEER analysis of 684 men treated with proton therapy 2002-2007 vs. matched IMRT cohort

    • IMRT associated with less GI “morbidity”

    • No significant differences in other toxicities

    • No difference in additional cancer therapy

      Sheets NC, et al, JAMA 2012

  • Medicare analysis of 421 men treated with proton therapy with 842 2008-2009 vs. matched IMRT cohort

    • Less GU toxicity at 6 mo for protons, which disappeared by 1 yr

    • No other significant differences

    • Proton therapy associated Medicare reimbursement costs were 75% higher than IMRT

      Yu JB, et al, JNCI 2013

Proton therapy vs imrt at penn medicine
Proton Therapy vs. IMRT (at Penn Medicine)

  • Proton Therapy vs. IMRT for Low or Low-Intermediate Risk Prostate Cancer

  • Currently recruiting

  • Sponsor: Massachusetts General Hospital

  • Collaborators:

    • University of Pennsylvania

    • National Cancer Institute (NCI)

  • Identifier: NCT01617161

  • Anticipated enrollment: 461

  • Primary Outcome Measures:

    • Compare the reduction in mean EPIC bowel scores at 24 mo