D de Jong, Prostate cancer brachytherapy


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  • The most commonly registered cancer in 2008 was prostate cancer, which accounted for 14 percent of registrations. Equates to 2500 new cases this year Treatments for various stages: Surgery Radiation therapy Androgen deprivation therapy (ADT) Active surveillance High dose rate Brachytherapy in combination with EBRT ( external-beam radiation therapy used for intermediate & high risk Used with and without ADT)
  • Low grade, normal except for a few key points. High grade, cells look nothing like original tissue. Adenocarcinoma, cancer made up of cells that surround the gland, epithelial cells
  • T describes the cancer itself, with different numbers explaining how large the cancer is. N stands for nodes and tells us if the cancer has spread to the lymph nodes. M tells if the cancer has spread, or become metastatic.
  • the cancer has started to grow outside of the gland, but with no spread to bones or lymph nodes. It can be seen growing into the fat that surrounds the prostate, or into the seminal vesicles or even into the base of the bladder.
  • Called interstitial radiotherapy, or brachytherapy , these improved methods offer the promise of a quick, minimally invasive treatment option, with good control in men with cancer confined to the prostate. Originally, gold or iodine seeds were placed surgically, but men continued to have problems with the return and spread of cancer. Newer seeds were developed, including iodine, iridium, palladium and more recently cesium . Each of these types of radioactive pellets gives off a calculated amount of radiation. Different seeds give off different levels of radiation Need to make the point that the radiation that we are looking at deals with effects of both beam and brachytherapy radiation Most often they are inserted through the skin of the perineum, just under the scrotum and in front of the anus. Because this procedure would otherwise be painful, it is done under anesthesia. This could be either general anesthesia where you are put to sleep, or a spinal or epidural anesthesia where just the area below the waist is anesthetized. Each seed is carefully placed in a predetermined location and depth as follows: A specially designed plastic template steers the preloaded needles into correct position. The position is confirmed with rectal ultrasound that is used to monitor the seed placement. The radioactive seeds are then inserted through these needles. external-beam radiation therapy (EBRT)? This is the term for a specific radiation technique used to treat many types of cancers in the body. Beams of high-energy radiation are focused from outside the body (hence external-beam ) onto the target area. 3-D conformal and IMRT (intensity modulated radiation therapy) therapy
  • When the hormone is eliminated from the body, the cancer generally stops growing and may actually go into a dormant phase, like going into hibernation.
  • QoL stuff: Note, possibly due to cancer as well as treatment Bowel symptoms might include irritation and blood in stools Likely that the QoL falls are down to IPSS, IIEF and other issues related to cancer.
  • Cesaretti, says that EF probably has also got to do with age as well as the prostate cancer
  • high dose rate brachytherapy
  • Cancer occupying one side and growing outside of the capsule, Fibrous outer lining of the prostate.
  • C30-Quality of life, measure designed to look at QoL in general for those suffering from cancer. QoL, PF, RF, SF, PA etc IPSS-Looks specifically at urinary function - 7 Questions, incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia PR25-Prostate cancer module. Looks at measures directly related to prostate cancer and its treatment. Urinary, incontinence, Bowel related, Treatment related, and sexual function Looks at androgen deprivation, in this case, looked to see whether hormone therapy interacted with the measures above EORTC stands for European Organisation for Research and Treatment of Cancer The IIEF is the International Index of Erectile Function, a 15 item scale, but we used the short form or IIEF-5 for this study.
  • These results will be spoken about when they appear to show a trend that actually started prior to the 6-18 month period. As groups were different, a t-test was done at baseline to test for comparability.
  • AGE GROUP INTERACTIONS NOT SIGNIFICANT WHEN EXAMINED FURTHER Of 83% with symptoms at baseline, 49% mild, 23% moderate and 1% severe. At 6-18 months, 37% mild, 28% moderate, 2% severe. At 22-27 months, 30% mild, 16% moderate, 3% severe. Here is the IPSS scoring guide.   0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic
  • Tells a nice overall story Also a short term effect going on here. In short term [1] young men sig worse at 3/12 than baseline [2] mid men sig worse at 3/12 than the young men at baseline [3] mid men sig worse at 3/12 than baseline
  • Bowel 74.52% with no symptoms, 44.35% at 6-18 months and 57.14% at 22-27 months
  • Treatment is based on issues surrounding side effects, a lot to do with maleness (e.g. Enlarged breasts or soreness etc) Also a short term effect happening:
  • Note also a significant fall here. And a short term effect happening also 4.08% functioning at 100% this fell to 0% from baseline
  • Again, a significant fall in these symptoms early on after treatment 16% reported 100% sexual function, fell to 0% at 22-27 months
  • All these findings are regardless of percentage affected.
  • All these findings are regardless of percentage affected.
  • D de Jong, Prostate cancer brachytherapy

    1. 1. Prostate Cancer Brachytherapy: Effects on Quality of Life & Sexual Function Dennis de Jong, Helen M Conaglen Leanne Tyrie, & John V Conaglen Sexual Health Research Unit Waikato Clinical School, Hamilton
    2. 2. Prostate Cancer
    3. 3. Types & Grades <ul><li>24 different types of prostate cancer identified (Palanisamy et al, 2010) </li></ul><ul><ul><li>Many slow growing, but some fast and aggressive </li></ul></ul><ul><li>On average 7 types of prostate cancers present in patients diagnosed </li></ul><ul><li>Most common type of prostate cancer is adenocarcinoma </li></ul><ul><li>Measures of malignancy </li></ul><ul><li>Low-grade to high grade </li></ul><ul><li>Gleason Scale (1-10) </li></ul><ul><ul><li>Cell appearance </li></ul></ul><ul><ul><li>Cell arrangement </li></ul></ul><ul><ul><ul><li>2-4 (Low Grade) </li></ul></ul></ul><ul><ul><ul><li>5-7 (Intermediate) </li></ul></ul></ul><ul><ul><ul><li>8-10 (High Grade) </li></ul></ul></ul><ul><li>Cancer tends to become more aggressive as it grows </li></ul>
    4. 4. Stages Treatments T1a Low grade cancer - active surveillance, radiation or prostatectomy T1b Aggressive treatment, radiation or prostatectomy T1c Depends on age, general health, and grade of cancer T2a/b Prostatectomy, radiation, hormone therapy an option for older men T3a/b/c Larger cancers - radiation, surgery, hormone treatment, or a combination of these T4a/b Usually spread beyond the prostate and to the lymph nodes. Treatment depends on health and age, but no known cure
    5. 5. Stages Treatments T1a Low grade cancer - active surveillance, radiation or prostatectomy T1b Aggressive treatment, radiation or prostatectomy T1c Depends on age, general health, and grade of cancer T2a/b Prostatectomy, radiation, hormone therapy an option for older men T3a/b/c Larger cancers - radiation, surgery, hormone treatment, or a combination of these T4a/b Usually spread beyond the prostate and to the lymph nodes. Treatment depends on health and age, but no known cure
    6. 6. Brachytherapy for PCa <ul><li>Seeds are inserted through the skin of the perineum </li></ul><ul><li>Each seed is placed in a predetermined location </li></ul><ul><li>Beams of high-energy radiation are focused on the target area </li></ul><ul><li>The radiation attempts to kill cancer cells in the affected area </li></ul>
    7. 7. Androgen Deprivation Therapy <ul><li>Prevents cancer cells absorbing testosterone, thereby reducing PSA </li></ul><ul><li>Often used along with other measures to prevent aggressive cancers from returning </li></ul><ul><li>Also used prior to surgery as it may reduce the size of the prostate, making surgery easier </li></ul>
    8. 8. Known Impacts of Brachytherapy <ul><li>Urinary and bowel issues </li></ul><ul><ul><li>Include urethritis (irritation) & incontinence, & minor bowel symptoms </li></ul></ul><ul><ul><li>Often improve over time (usually within months) </li></ul></ul><ul><ul><li>Percentage affected varies across studies </li></ul></ul><ul><ul><li>(Bottomley et al., 2010; Quek & Penson, 2005) </li></ul></ul><ul><li>Quality of life </li></ul><ul><ul><li>Reductions in physical well being and role functioning compared to baseline* </li></ul></ul><ul><ul><li>(Quek & Penson, 2005) </li></ul></ul>
    9. 9. <ul><li>Sexual dysfunction </li></ul><ul><ul><li>Many studies report  in erectile dysfunction after brachytherapy (Bottomley et al., 2005; Cesaretti et al., 2007; Quek & Penson, 2007) </li></ul></ul><ul><ul><li>High levels of Erectile Function (EF) and younger age before treatment strongly predict maintenance of EF after brachytherapy </li></ul></ul><ul><ul><li>(Cesaretti et al., 2007) </li></ul></ul>Known Impacts of Brachytherapy
    10. 10. Known Impacts of Brachytherapy <ul><li>Probable that issues associated with prostate cancer and brachytherapy are multi-factorial </li></ul><ul><ul><li>Age </li></ul></ul><ul><ul><li>General health </li></ul></ul><ul><ul><li>Lifestyle factors </li></ul></ul><ul><li>Effects can be described as </li></ul><ul><ul><li>Short term: occurring < 6 months from start of treatment </li></ul></ul><ul><ul><li>Long term: occurring after 6 months into treatment </li></ul></ul>
    11. 11. Study Aims <ul><li>To investigate the impact on the prostate symptoms of brachytherapy </li></ul><ul><li>To understand the impact on a man’s quality of life as result of brachytherapy </li></ul><ul><li>To compare the effect of ADT on all of these areas – did QoL, prostate symptoms and sexual function worsen due to ADT? </li></ul>
    12. 12. Methodology <ul><li>Data collected by the Waikato Regional Cancer Unit over 5 years - entered but not analysed </li></ul><ul><li>Studentship task to analyse data relating to quality of life </li></ul><ul><li>Involved conversion of data to form useable in statistics package; challenges due to non-return of questionnaires, and thus intermittent time-points across group </li></ul><ul><li>Dataset describes men with ≥ 3 assessment data points; baseline, mid-point (6-18 months) & 2 years (22-27 months) </li></ul>
    13. 13. Study Sample Participants 161 men aged 48-84 years [Mean 66.4 yrs, SD 6.9] Cancer Grades T1c to T3c, with a mode of T3a Gleason Scores Range: 6 to 10 [Mean 7, SD 0.9] PSA Range: 2.2 to 230 [Mean 17.1, SD 21.8] Brachytherapy without ADT 89 men Brachytherapy with ADT 72 men Short-term effects sub-group (0-3 months) 48 men with age, grades, Gleason Scores, & PSA similar to men above
    14. 14. Measures <ul><li>IPSS: prostate symptom scale </li></ul><ul><li>EORTC-C30: quality of life with cancer </li></ul><ul><li>EORTC-PR25: prostate specific queries </li></ul><ul><li>ADT data from patient notes </li></ul><ul><li>IIEF-5: Brief erectile function scale </li></ul>
    15. 15. Analyses <ul><li>Repeated measures analysis of variance over time for each variable </li></ul><ul><ul><li>Time: Baseline, 6-18 months, 22-27 months </li></ul></ul><ul><li>Between subjects factors were: </li></ul><ul><ul><li>Age group (3 groups: <60, 60-69, 70+ years) </li></ul></ul><ul><ul><li>ADT Tx (2 groups – no Tx or ADT Tx) </li></ul></ul><ul><li>Where apparently significant ANOVAs found, post hoc analyses were not always significant because of uneven group sizes etc </li></ul><ul><li>Reporting today on significant findings </li></ul>
    16. 16. IPSS: Total <ul><li>83% with symptoms at baseline </li></ul><ul><li>69% with symptoms at 22-27 months </li></ul><ul><li>IPSS did not worsen over time with therapy, but ADT Tx effect was significant, p <.05 </li></ul><ul><li>Men on ADT Tx sig worse: </li></ul><ul><ul><li>at baseline than non-ADT men at 6-8 months, p <.01, </li></ul></ul><ul><ul><li>and 22-27 months, p <.05 </li></ul></ul>
    17. 17. EORTC-30: However, all NZ levels significantly better than general EORTC norms taken across all treatment options Scale Main Effect Post hoc General QoL Time, p <.05 Sig worse at two years than baseline, p <.05 Physical Function Time, p <.01 Sig worse at two years than baseline, p <.05 Role Function Time, p <.05 Sig worse at two years than baseline, p <.05 Social Function Time, p <.01 Sig worse at mid-point than baseline, p <. 05, and two years than baseline, p <. 001
    18. 18. EORTC PR25: Urinary <ul><li>15% men had no symptoms at baseline </li></ul><ul><li>5% men had no symptoms at 22-27 mths </li></ul><ul><li>Sig main effect of Time, p <.0001 </li></ul><ul><li>Post hoc: Baseline values sig lower than 6-18 months, p <.01 or 22-27 months, p <.0001 </li></ul><ul><li>Sig interaction with ADT Tx, p <.05 </li></ul>
    19. 19. PR25: Urinary – short term <ul><li>Significant interaction between age group and time effect on urinary symptoms, p <.05 </li></ul>
    20. 20. PR25: Bowel <ul><li>Baseline: 75% men had no symptoms </li></ul><ul><li>6-18 mths: 44% men had no symptoms </li></ul><ul><li>22-27 mths: 57% men had no symptoms </li></ul><ul><li>Main effect of Time, p <.01, worse at 22-27 months than baseline </li></ul><ul><li>Short term sig more symptoms at 3 months, </li></ul><ul><li>p <.01 </li></ul>
    21. 21. PR25: Treatment side effects <ul><li>Main effect of Time, p <.0001. </li></ul><ul><ul><li>Post hoc: More side effects at 6-18 months, p < .0001 & 22-27 months, p < .0001 than baseline </li></ul></ul><ul><li>Sig interaction with Age Group, p < .05 </li></ul><ul><ul><li>Younger men had more side effects than two older groups at 6-18 & 22-27 months </li></ul></ul><ul><li>Short term analysis showed this impact present at 3 months also </li></ul>
    22. 22. EORTC PR25: Sexual Function <ul><li>Sig main effect of Time, p <.0001 </li></ul><ul><li>Function at baseline better than at mid-pt, p <.01 or 22-27 months, p <.0001 </li></ul><ul><li>Hormone deprivation therapy analysis, ns </li></ul>NO ADT ADT Tx
    23. 23. EORTC PR25: Sex Cond Fn <ul><li>Questions men about sexual function if sexually active </li></ul><ul><ul><li>16% reported 100% sexual function at baseline </li></ul></ul><ul><ul><li>0% @ 22-27 months </li></ul></ul><ul><li>Too few men in each age group to analyse with age & hormone factors over time </li></ul><ul><li>1-way ANOVA shows oldest men sig less functional at baseline, p < .01 </li></ul><ul><ul><li><60 yrs: M=82.9 ± 15.3 [n=19] </li></ul></ul><ul><ul><li>60-9 yrs: M=74.8 ± 24.3 [n=39] </li></ul></ul><ul><ul><li>70+ yrs: M=52.5 ± 25.5 [n=17] </li></ul></ul><ul><li>No sig diffs at other times </li></ul>
    24. 24. IIEF-5 Sexual Function
    25. 25. Effect of Time & ADT on IIEF-5 Sig effect of time: F(2, 60)=10.888, p =.00009 No effect of ADT, nor interaction.
    26. 26. IIEF-5 sub-scales over Time
    27. 27. Short or Long Term Effects? Sig change from baseline to 3 months: t (15) = 2.96, p < .01
    28. 28. Conclusions <ul><li>IPSS symptoms did not significantly worsen over time Impact was affected by ADT and the age of the men </li></ul><ul><li>Men undergoing brachytherapy reported worsening urinary prostate symptoms initially and these continued to get worse </li></ul><ul><li>Men undergoing brachytherapy reported negative impacts on general quality of life, physical function, role function and social function over the two year time-frame </li></ul><ul><li>Impacts on QoL less in NZ study than in EORTC data </li></ul>
    29. 29. Conclusions <ul><li>Sexual Function from EORTC-PR25, was reduced in the short term and did not improve with time </li></ul><ul><li>Sexual function from IIEF-5 worsened at each time point </li></ul><ul><ul><li>Short-term impact found at 3 months was ongoing </li></ul></ul><ul><li>What is impact over longer time-frame? </li></ul><ul><ul><li>At ~ 2 years, nothing appears to return to normal functioning </li></ul></ul><ul><ul><li>However, other studies show many functions and symptoms do appear to stabilize, and claim improvement, over longer time periods </li></ul></ul><ul><li>What is impact on partners of these men, and their relationships? </li></ul><ul><ul><li>Seeking funding for studies, pilot just underway </li></ul></ul>
    30. 30. Acknowledgements <ul><li>Thanks go to: </li></ul><ul><li>The men who have completed all the paperwork over the years the data has been collected </li></ul><ul><li>Those who have entered the data at various times – special mention of Ali Gisler, who managed the data collection </li></ul><ul><li>The Waikato Clinical School for the Summer Studentship opportunity to analyse the data </li></ul>