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Erectile dysfunction after prostate three-dimensional conformal radiation therapy. Correlation with the dose to the penile bulb, "Beyond the Abstract," by Alessandro Magli, MD

BERKELEY, CA (UroToday.com) - Prostate cancer is the most common non-skin cancer and the second most common cause of cancer death in men.[1] For the majority of men with incident prostate cancer (approximately 85%), the disease is diagnosed as localized (T1-2). When the disease is organ confined the definitive treatment options commonly include: radical prostatectomy, external beam radiation therapy (EBRT), and brachytherapy.

Evidence suggests that among these treatment modalities, brachytherapy is associated with the lowest risk of erectile dysfunction (ED). In a meta-analysis of patients treated for localized prostate cancer, the predicted probability of maintaining erectile function after 1 year was 76% with brachytherapy, 55% with EBRT, and 34% with nerve-sparing radical prostatectomy.[2] However, this improved rate of potency preservation may not persist with longer follow-up.[3]

Few studies have evaluated sexual function after 3D-CRT as compared to pre-treatment baseline [4] but complete pre and post 3D-CRT sexual-function data are critical for mandatory assessment. The purpose of this study was to determine whether the radiation dose delivered to the penile bulb (PB) during definitive 3D-CRT for prostate cancer correlates with the development of impotence.

In our study, the Dmean was found to be more predictive than the D50 normally quoted, because differences only became apparent as the dose accumulated with the increasing volume irradiated. Nevertheless the difference between these two dose–volume parameters is small and clinically negligible. Most studies suggest a median dose (D50) of 350 Gy as a cut-point over which there is a higher chance of developing potency.[5, 6, 7] Our results illustrate that impotent patients received Dmean ≥50 Gy compared to those who maintained potency above this dose level.

Although the number of patients in our study is small and the range of doses to the PB is broad and overlapping, we believe that these results warrant the use of pelvic magnetic resonance imaging (MRI) in addition to CT to improve the localisation of the prostate apex and of the penile bulb and consequently resulted in a reduction of the dose to the bulb, independently of the delivery technique (intensity modulated radiotherapy – helical tomotherapy).[8, 9] By contrast, other authors [10, 11, 12] have reported on the use of IMRT to administer a reduced dose to critical structures such as the rectum and bulb of the penis. These techniques have the potential to improve the preservation of potency further by minimizing the bulb dose. Also the incorporation of adaptive image-guided radiotherapy (IGRT) reduces the risk of geometric miss and results in excellent biochemical control and low toxicities to organs at risk.[13]

Since 2009, in our department, patients with localized prostate cancer were treated with IGRT with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers and the definition and delineation of PB and CTV by MRI-3T images. Sildenafil improves the erectile function in 71% of patients with radiation-induced erectile dysfunction.[14] It is likely that sparing the PB during radiotherapy will improve the efficacy of such medical therapies for impotence.

Our data suggest that a dose-volume relationship between the dose to the PB and radiation-induced impotence may exist. The SF scores have a significant decrease from baseline at 6 months after EBRT, compared to degradation from 6 to 24 months. Moreover, in agreement with other investigators, there is a correlation between SF after RT and SF score before the initiation of treatment.[15,16] This information can help patients to have realistic expectations of the treatment outcomes.

Since Dmean ≥ 50 Gy is associated with a significant risk of erectile dysfunction, we propose a threshold dose for preservation of potency lie between 40-45Gy. Longer follow-up is needed to validate our results as potency appears to decrease with time after radiotherapy.[17] We hope to incorporate the findings from this study into the development of future studies looking at refining the dose constraints for the PB and associated proximal penile tissue for high-dose IMRT with gold fiducial markers.

References:

  1. Merrick GS, Butler WM, Lief JH, Dorsey AT. Is brachytherapy comparable with radical prostatectomy and external-beam radiation for clinically localized prostate cancer? Tech Urol 2001; 7: 12–9.
  2. Robinson JW, Moritz S, Fung T. Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma. Int J Radiat Oncol Biol Phys 2002 ; 54: 1063 – 8.
  3. Merrick GS, Wallner KE, Butler WM. Management of sexual dysfunction after prostate brachytherapy. Oncology (Wilston Park) 2003; 17: 52–62.
  4. Turner SL, Adams K, Bull CA, Berry MP. Sexual function after radical radiation therapy for prostate cancer: A prospective evaluation. Urology 1999; 54: 124 –9.
  5. Fisch BM, Pickett B, Weinberg V, Roach M. Dose of radiation received by the bulb of the penis correlates with risk of impotence after three-dimensional conformal radiotherapy for prostate cancer. Urology 2001; 57: 955–9.
  6. Merrick GS, Wallner K, Butler WM et al. A comparison of radiation dose to the bulb of the penis in men with and without prostate brachytherapy-induced erectile dysfunction. Int J Radiat Oncol Biol Phys 2001; 50: 597–04.
  7. Roach M, Winter K, Michalski JM et al. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: findings from a prospective, multi-institutional, phase I/II dose–escalation study. Int J Radiat Oncol Biol Phys 2004; 60: 1351–6.
  8. Perna L, Fiorino C, Cozzarini C et al. “Sparing the penile bulb in the radical irradiation of clinically localised prostate carcinoma: A comparison between MRI and CT prostatic apex definition in 3DCRT, Linac-IMRT and Helical Tomotherapy” Rad Oncol 2009;93:57–63.
  9. Hentschel B, Oehler W, Strauss D et al. Definition of the CTV prostate in CT and MRI by using CT-MRI image fusion in IMRT planning for prostate cancer. Strahlenther Onkol 2011; 187: 183-90.
  10. Ghadjar P, Gwerder N, Manser P et al. High-dose (80 Gy) intensity-modulated radiation therapy with daily image guidance as primary treatment for localized prostate cancer. Strahlenther Onkol 2010; 186: 678-92.
  11. Guckernbergen M, Ok S, Polat B et al. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. Strahlenther Onkol 2010; 186: 535-43.
  12. Geier M, Astner ST, Duma MN et al. Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy. Strahlenther Onkol 2012; 188: 1-7.
  13. Park SS, Di Yan, McGrath S, Dilworth JT et al. Adaptive image-guided radiotherapy (IGRT) eliminates the risk of rectal distension in prostate cancer treatment planning: clinical evidence. Int J Radiat Oncol Biol Phys 2012; 83: 947–52.
  14. Kedia S, Zippe CD, Agarwal A et al. Treatment of erectile dysfunction with sildenafil citrate (Viagra) after radiation therapy for prostate cancer. Urology 1999; 54: 308 –12.
  15. Di Blasio CJ, Malcolm JB, Derweesh IH, et al. Patterns of sexual and erectile dysfunction and response to treatment in patients receiving androgen deprivation therapy for prostate cancer. BJU Int 2008; 102: 39–43.
  16. van der Wielen GJ, van Putten WL, Incrocci L et al. Sexual function after three-dimensional conformal radiotherapy for prostate cancer: Results from a dose-escalation trial. Int J Radiat Oncol Biol Phys 2007; 68: 479–84.
  17. Zelefsky MJ, Eid JF. Elucidating the etiology of erectile dysfunction after definitive therapy for prostatic cancer. Int J Radiat Oncol Biol Phys 1998; 40: 129 –33.

 

Written by:
Alessandro Magli, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Radiotherapy Dept.
Ospedale S. Maria della Misericordia
Piazzale S.Maria della Misericordia, 15
Udine, Italy

Erectile dysfunction after prostate three-dimensional conformal radiation therapy. Correlation with the dose to the penile bulb - Abstract

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