Questions to ask on a first visit for primary radiation therapy (IGRT/IMRT)

IGRT/IMRT Questions for Doctors

1. How many have you planned? 
2. How has your practice of IMRT changed over the years? 
3. What is your 5-yr freedom from recurrence rate for patients at my risk level? 
4. What proportion of your recurrences were local? (see this link) 
5. What kind of urinary and rectal reactions can I expect? 
• How long can I expect them to last? 
• What medications or interventions do you typically give for that? 
• Should I expect those symptoms to recur later? 
6. What is your rate of serious (Grade 3) adverse events? 
7. Do you see urinary strictures? 
8. Urinary retention requiring catheterization? Fistulas? 
9. Rectal bleeding requiring argon plasma or other interventions? 
10. What is the margin you will treat around the prostate? 
• Is it less on the rectal side? 
11. Will you include the pelvic lymph nodes? 
12. What about the seminal vesicles -proximal or entire? 
13. What are the prescribed doses to the planned target volumes? 
14. If applicable, in light of my unfavorable risk cancer: 
• do you think I need a brachytherapy boost to the prostate? (see this link) 
• do you think I need hormone therapy? For what duration?
15. In light of the 8 major randomized clinical trials on hypofractionation reported in the last year (see this link), do you recommend hypofractionation (fewer treatments) for me? 
16. Does your hospital do SBRT monotherapy for patients like me? Why not? 
17. Do you work off a fused MRI/CT scan for the plan? 
18. What machine do you use? (any brand of VMAT or Tomotherapy are good) 
19. Do you use fiducials or Calypso transponders? 
• Do you do transperineal placement of them? 
20. What system do you use for inter-fractional tracking? (cone beam CT or stereoscopic X-ray, probably) 
21. Is the alignment automated? 
22. In my treatment plan, what do you identify as “organs at risk” and what dose constraints do you put on them? 
• What dose will my penile bulb receive? 
23. Do you use angiography to locate and spare the pudendal artery? (see this link) 
24. How long does each treatment take? 
25. How will I be immobilized during each treatment? 
26. Are there any bowel prep or dietary requirements? 
27. Should I avoid taking antioxidant supplements during treatment? 
28. In your practice, among men who were fully potent, what percent remained fully potent 3-5 years later? 
29. Have any men retained some ability to produce semen? 
30. What is your opinion of taking Viagra preventatively? (see this link) 
31. Do you monitor side effects with the EPIC questionnaire? 
32. In your practice, what percent of men experience acute urinary side effects? 
33. In your practice, what percent of men experience acute rectal side effects? 
34. In your practice, what percent of men experience late term urinary side effects? 
35. In your practice, what percent of men experience late term rectal side effects? 
36. What kind of PSA pattern should I expect following treatment? 
37. What is the median PSA nadir you are seeing in your practice, and how long does it take to reach that, on the average?
38. If there should be a biochemical (PSA) recurrence, what would the next steps be? (they have to prove it’s local but not distant) 
39. Have you ever used SBRT, brachy, or cryo for salvage after a local IMRT failure, and was that focal or whole gland? 
40. Are you open to email communications between us?

Site of recurrence after primary radiation therapy

This is the first of a two-part commentary. In this part, we look at studies that identified the site of failure after primary radiation treatment. In next part, we will look at how SBRT is being used to treat such local recurrences.

Before any kind of treatment is given for a recurrence only detected via rising PSA, it’s important to assure that it is indeed only a local recurrence. If there are already distant metastases, local salvage treatment would only create side effects without cancer control. In the past, we only had bone scans and CT scans that could detect only the larger metastases. New imaging technologies are enabling us to better assess the recurrence site.

Hannequin et al. posted the results of their study (abstract 23) at last week’s Genitourinary Conference. The authors retrospectively looked at 89 patients treated in Paris, France between 2010 and 2014 with either brachytherapy (23 patients) or EBRT (66 patients) and who had a biochemical recurrence detected as a rising PSA of at least 2.0 ng/ml over its lowest level.  The patients were classified at diagnosis as favorable risk (28%), intermediate risk (39%) or unfavorable risk (33%). They all had an 18-FCH-PET scan and may have had a multiparametric MRI as well. In 20 patients (22.5%), no target lesion could be clinically identified. Among the 69 patients in whom a clinically detected recurrence was identified, the recurrence site was as follows:

• ·      Local recurrence in 35 patients (51%)
• ·      Lymph node recurrence in 22 patients (32%)
• ·      Distant metastases in 12 patients (17%)

All of those 57 patients with local or lymph node recurrence (83%) were deemed eligible for salvage radiation, but only 17 (25%) could have it. The reasons for not having salvage radiation included advanced age, poor performance status, extensive disease, and patient refusal.

Zumsteg et al. published a retrospective analysis of 2,694 patients treated with external beam RT (IMRT or 3D-CRT) at Memorial Sloan Kettering Cancer Center between 1991 and 2008. The patient diagnosis and treatment characteristics were as follows:

• ·      Risk category:

o   Low risk: 22%

o   Intermediate risk: 48%

o   High risk: 30%

• ·      Median age: 69
• ·      Adjuvant ADT received: 54%, median of 6 months
• ·      Radiation dose received:

o   75.6 Gy (17%)

o   79.2-82.8 Gy (43%)

o   86.4 Gy (40%)

Local recurrence (prostate and seminal vesicles) was clinically detected mostly (71%) via biopsy, the rest radiographically (MRI or PET scan). Lymph node recurrences were detected by CT scan, and distant recurrences were clinically detected via biopsy, by radiographic response to ADT, or by rapidly rising PSA during the castrate-resistant phase. After 83 months of followup overall, and 111 months of followup on clinically recurrent patients:

• ·      22.6% had a biochemical recurrence, defined as nadir+2
• ·      17.6% had a clinically detected recurrence.
• ·      Recurrence by risk category:

o   Low risk: 5.8%

o   Intermediate risk: 13.4%

o   High risk:  32.8%

• ·      Recurrence by radiation dose:

o   75.6 Gy: 29.1%

o   79.2-82.8 Gy: 14.6%

o   86.4 Gy:  15.8%

• ·      Recurrence was also higher in men under 70, higher stage, PSA>10, >50% positive cores.

Among those in whom a clinical recurrence was detected within 8 years of primary treatment, the site of the first recurrence was as follows:

• ·      Local recurrence in 55%

o   74% in low-risk recurrent patients

o   68% in intermediate-risk recurrent patients

o   45% in high-risk recurrent patients

o   in 87% of local recurrences, it was the only recurrence site

• ·      Pelvic lymph nodes (PLN) in 21%*

o   None in low-risk recurrent patients

o   in 38%, of PLN recurrences, it was the only recurrence site

• ·      Abdominal lymph nodes in 9%
• ·      Thoracic lymph nodes in 2%
• ·      Bone in 34%

o   40% in high-risk recurrent patients

o   in 66% of bone recurrences, it was the only recurrence site

• ·      Viscera in 2%

*Patients who presented with enlarged nodes were excluded, and no one received whole pelvic radiation.

The authors also note that a first isolated PLN recurrence was a rare event among all the men treated with EBRT, only occurring in 1.5% of them.

The site of recurrence was strongly correlated with prostate cancer-specific mortality. Compared to locally recurrent prostate cancer, the risk of prostate cancer death after a median of 111 months of followup was:

• ·      4.2 times higher for lymph recurrences
• ·      8.1 times higher for bone recurrences
• ·      9.6 times higher for multi-organ/visceral recurrences

In fact, after accounting for the site of recurrence, only the Gleason score, but none of the other risk factors (e.g., PSA kinetics, stage, age, time to recurrence), predicted prostate cancer mortality. This, and the fact that a first recurrence site was often the sole recurrence site, suggests that there are different types of prostate cancer (phenotypes) with characteristic patterns of spreading and characteristic virulence.

The authors draw 3 conclusions:

“1) The prostate is the most common initial site of recurrence in patients in all risk groups with an increasing absolute incidence that correlates with increasing NCCN risk group.  

2) Isolated PLN relapse is rare in all patients, including those at high risk treated without elective PLN irradiation, at least when using CT for detection.

3) Tumors in many patients display a tropism for specific anatomical compartments and these anatomical patterns of recurrence independently predict prostate cancer specific mortality after clinically detected recurrence.

Unfortunately, their report doesn’t show the time to first recurrence broken down by recurrence site. It may be that the much shorter followup in the French study (patients were treated 2-6 years ago) may explain the lower incidence of bone metastases in that study. Detection methods may explain the differences as well.

In both studies, more than half of the recurrences after primary radiation therapy were local and were at least potentially treatable with salvage therapies. That may not hold true for other kinds of radiation. There isn’t a lot of data on recurrence sites, but the higher biologically effective doses available with SBRT, HDR monotherapy, and multi-modal radiation may be better able to overcome the more radio-resistant cells. In a recent commentary, we saw that a novel kind of radiation, called Carbon Ion Radiotherapy, could kill cancer cells even in a low-oxygen (hypoxic) tumor environment.

The table below shows the range of biologically effective doses for various radiation modalities, and the percent of local failures in all treated patients (not just those with a recurrence), broken out by risk group where available.

Percent Local Failures by Risk Group

	EBRT	SBRT	HDR brachy monotherapy	EBRT+HDR brachy boost
Relative biologically effective dose*	.89-1.02	1.06-1.17	1.27-1.36	.97-1.17
Low Risk	4%	0.9%	2.5%	1%
Intermediate Risk	9%	2.6%		1%
High Risk	15%	7%		9%
Followup	9 years	6/7 years	10 years	4 years
Reference	Zumsteg et al.	Katz and Kang Katz and Kang	Hauswald et al.	Kamrava et al.

*Relative to 80 Gy of IMRT for cancer control

The local failure rates seem to be higher for EBRT than for SBRT, HDR brachy monotherapy, or HDR brachy boost therapy. Only a randomized comparative trial can decide what relative role biologically effective doses, radiation intensity, patient selection, and detection techniques play in determining the extent of local control. It would be useful to know as well whether genetic tests like Prolaris or Oncotype Dx can predict local response to radiation, and whether there are identifiable subtypes that metastasize to lymph nodes, bones or viscera. Better detection of local and distant recurrence is needed as well.

In the next commentary, we will look at how SBRT is being used in salvage treatment of those isolated local recurrences.

written January 13, 2016

Adverse Effects of Primary IMRT

A recent commentary listed some of the most common adverse effects of prostatectomy, some of which (e.g., perceived penile shrinkage, climacturia, Peyronie's, stress incontinence) are seldom mentioned by urologists to prospective patients, and are not routinely included in standardized quality-of-life questionnaires. In the interest of providing equal time to the potential adverse effects of radiation, below is a list of such effects, ranked by approximate incidence, for primary IMRT.

This list only applies to primary IMRT and not to salvage treatments, which may have a very different side effect profile. These data are not purely for IMRT – they include some patients treated with 3D CRT as well. Some patients in these studies may have had adjuvant ADT, so it is impossible to distinguish the effects of radiation from the effects of concurrent hormone treatment. None of this applies to SBRT or brachytherapy.

Most of the data on acute side effects are pulled from the Sanda et al. study, which represents the patient-reported outcomes at 9 of the top US institutions, and is not indicative of community practice. Many of the late-terms side effects are given as their absolute incidence. Acute side effects are given as increases over baseline function (indicated by “+”). Unless otherwise specified, they are acute side effects (within 3 months of treatment), rather than late-term or chronic side effects. Acute side effects are typically transient. Contrary to “common knowledge,” new side effects rarely emerge after 2 years.

In general, urinary, rectal and sexual adverse effects will be worse among men whose function is impaired before treatment, and those with certain comorbidities. Radiation dose, image guidance techniques, margins, anatomic differences, and sensitivity to radiation contribute to individual variances in side effects. Most of the side effects are attributable to inflammation (cystitis, urethritis, proctitis), spasms (diarrhea, bladder spasms), and the destruction/fibrosis of vascular and other tissues (ED, urinary retention). There are treatments available for many of these adverse effects. Patients are advised to discuss them with their doctors.

Loss of semen (5 yrs) 89%

Fatigue 32%

Sexual function- big/moderate problem (1 yr) 31%

Frequent urination +18%

Vitality/hormonal function – big/moderate problem (1 yr) 18%

Bowel urgency  +15%

Bowel frequency +14%

Urinary irritation or obstruction – big/moderate problem (1 yr) 14%

Bowel/rectal function – big/moderate problem (1 yr) 11%

Dysuria (pain while urinating) +11%

Weak stream +10%

Leaking >1x per day +9%

Rectal pain +5%

Fecal incontinence +5%

Dribbling +4%

Urinary incontinence – big/moderate problem (1 yr) 4%

Any pad use +3%

Bloody stools +2%

Other rare effects with <1% incidence:

Rectourethral fistula

Bladder neck contracture requiring surgical intervention

Second primary pelvic cancer

------------

Sources:

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors (Sanda et al.)

Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial

Radiotherapy-induced second primary cancer (RTSPC) risk is low and may differ by radiation technique.

Urorectal fistulae following the treatment of prostate cancer

Second primary cancers after radiation for prostate cancer: A systematic review of the clinical data and impact of treatment technique

ADT and radiation for first-line treatment of node-positive (N1) prostate cancer (STAMPEDE trial details)

In a previous commentary, we mentioned the early top-line results of the STAMPEDE trial, which demonstrated a benefit to whole-pelvic radiation and ADT for treatment of high risk prostate cancer when positive pelvic lymph nodes have been detected. We now have some additional details.

James et al. analyzed data from the control arm of the STAMPEDE trial. The control arm excluded patients with distant metastases and those who had previous treatment. All patients were high risk and were treated between 2005 and 2014 with a minimum of two years of ADT. At physician’s discretion, some were also treated with RT 6-9 months after the start of ADT. Patients with lymph nodes larger than 10 mm were typically staged as “node positive” (N1). Patient counts for this analysis were as follows:

• ·      N0 and RT – 121 patients – 43% received whole pelvic radiation
• ·      N0 and no RT – 46 patients
• ·      N1 and RT -  71 patients - 82% received whole pelvic radiation
• ·      N1 and no RT -  86 patients

Age, Gleason scores, and performance status were similar in all groups. Pre-treatment PSA was higher in patients who had RT, although the differences were not statistically significant. The planned radiation dose to the prostate and seminal vesicles was 74 Gy in 37 fractions or the equivalent hypofractionated dose. The planned dose to the pelvic lymph nodes was 46-50 Gy in 23-25 fractions or 55 Gy in 37 fractions. Increased doses were allowed if the physician was experienced in delivering nodal doses.

Although overall survival was measured, there was too little mortality as of this interim analysis to be worth reporting. Instead, the authors focused on 2-year Failure-Free Survival (FFS), defined as no biochemical recurrence, and no radiographically-detected progression among survivors. Patients would have been ADT-free for 12-15 months by that point, unless they showed early evidence of progressing.

Among the men with no detected nodal involvement( N0):

• ·      The 2-yr FFS was:

o   96% among men who received RT

o   73% among men who did not receive RT

• ·      Late GI toxicity was:

o   Proctitis: Grade 2: 7%, Grade 3: 2%

o   Diarrhea: Grade 2: 3%, Grade 3: 1%

o   Rectal ulcer: Grade 3: 1%

• ·      Late GU toxicity was:

o   Cystitis: Grade 2: 2%, Grade 3: 1%

o   Hematuria: Grade 2: 3%, Grade 3: 1%

Among the men with detected nodal involvement (N1):

• ·      The 2-yr FFS was:

o   89% among men who received RT

o   64% among men who did not receive RT

• ·      Late GI toxicity was:

o   Proctitis: Grade 2: 8%

o   Diarrhea: Grade 2: 6%

• ·      Late GU toxicity was:

o   Cystitis: Grade 2: 5%

o   Hematuria: Grade 2: 2%, Grade 3: 2%

Although this was a prospective study, patients were not randomized to receive RT or not, so there may be selection bias at work. The higher pretreatment PSA in the patients who did not get RT suggests that they may have been considered to be too far progressed to benefit from radiation. However, the benefit of RT was maintained even after adjustment for pretreatment PSA, age and Gleason score.

The planned radiation dose, 74 Gy, is lower than the 80 Gy now considered to be curative. The dose delivered to the pelvic lymph nodes is still within the standard of care. Although almost half of those with no nodal involvement were treated with whole pelvic RT, there was no analysis of benefit in that subgroup.

RT clearly delayed the time to relapse among high-risk patients, regardless of nodal status. The FFS curves continued to diverge after 2 years, indicating a lasting effect of treatment, at least out to 5 years post-treatment. Long-term toxicity was low among all patients who received RT.

Subject to the above caveat on selection bias, this early analysis indicates that men with high risk prostate cancer, whether they had detected nodal involvement or not, benefited from long-term ADT+RT. As there was little long-term toxicity attached to this decision, there seems little reason to withhold such treatment.

The questions mentioned in our earlier commentary continue to be important:

• What is the most appropriate radiation dose?
• Is there a limit to the number of infected nodes beyond which it is fruitless to use RT?
• Should simultaneous integrated boost RT be used on infected nodes?
• Can SBRT equal or improve the risk/benefit profile over IMRT?
• What is the best timing for neoadjuvant/concurrent/adjuvant ADT?
• Can outcomes be improved with docetaxel?
• Can outcomes be improved with immunotherapy?
• Is whole pelvic RT or ePLND more effective?
• Can staging be improved with new imaging techniques?
• What are the patient risk factors that affect oncological control and toxicity?
• How much of the improved survival is a delay due to cytoreduction, and how much is actual cure?

Declining use of RT in treating clinical stage T3 patients and those with adverse pathology after surgery

Patients clinically diagnosed with prostate cancer outside of the prostate capsule (stage cT3), are increasingly treated with radical prostatectomy (RP) rather than with primary radiation therapy (RT). In addition, patients who have adverse pathological features after first-line surgery (stage pT3 and/or positive margins) are increasingly not receiving either adjuvant or early RT.

Nezolosky et al. looked at the SEER database records of 11,604 patients clinically diagnosed with stage T3 prostate cancer from 1998 to 2012. They found:

• ·      RP use increased from 12.5% to 44.4%.
• ·      RT use decreased from 55.8% to 38.4%
• ·      “No treatment” decreased from 31.7% to 17.2%
• ·      For extracapsular extension (stage T3a), RP use was 49.8% vs. 37.1% for RT in 2012.
• ·      For seminal vesicle invasion (stage T3b), RP use was 41.6% vs. 42.1% for RT in 2012.
• ·      RT use exceeded RP by 59% if the biopsy Gleason score was 8-10.
• ·      RT use exceeded RP by 3% among those with higher PSA, and by 7% among older patients.

This trend is troubling because RP for cT3 is often not curative. The following biochemical recurrence-free survival rates have been reported and are very consistent:

• ·      Mitchell et al. (Mayo Clinic): 41% after 20 years for cT3 patients.
• ·      Freedland et al. (Johns Hopkins): 49% at 15 years for cT3a patients.
• ·      Carver et al. (Memorial Sloan Kettering): 44% at 10 years for cT3 patients.
• ·      Hsu et al. (Leuven, Belgium): 51% at 10 years for cT3a patients.
• ·      Xylinas et al. (Paris, France): 45% at 5 years for cT3 patients.

The rates are similar among those diagnosed with stage T3 at pathology. Hruza et al. reported bRFS of 47% and 50% for those staged pT3a and pT3b respectively. Pagano et al. reported bRFS of 40% for those staged pT3b. Watkins et al. found that 40% of pT3 surgical patients had already biochemically relapsed after a median of 18 months.

There are other factors that affect recurrence prognosis after surgery. Age, a high pre-treatment PSA, high Gleason score, positive surgical margin (including its size and Gleason score at the margin), and the length of extraprostatic extension (EPE) are all risk factors (see Fossati et al., Djaladat et al., Ball et al., Jeong et al.). In the Watkins et al. study, patients with EPE and negative surgical margins biochemically relapsed at the rate of 0%, 28% and 63% for Gleason scores of 6, 7 and 8-10, respectively. However, if the surgical margins were also positive, the relapse rates were significantly worse: 33%, 50%, and 71% for Gleason scores of 6, 7 and 8-10, respectively. Briganti et al. found that the 5-year bRFS was 55.2% among surgical patients categorized as high risk, which includes stage T3, Gleason score 8-10 or PSA>20 ng/ml.

Can primary radiation alone do any better? I haven’t seen breakdowns for stage cT3 patients specifically, but we have long-term follow up in many clinical trials where high-risk patients were treated with radiation and ADT. Here are some bRFS results we discussed recently:

• ·      HDR brachy monotherapy: 77 – 93% (3-8 years)
• ·      HDR brachy boost + EBRT: 66 - 96% (5-10 years)
• ·      LDR brachy monotherapy: 68% (5 years)
• ·      LDR brachy boost + EBRT:  83% (9 years)
• ·      EBRT monotherapy: 71 - 88% (5 years)

While primary radiation typically does about 50-100% better than primary surgery at controlling the cancer, urologists often argue that adjuvant or salvage RT will bring the numbers into line. There is an ongoing randomized clinical trial (NCT02102477) among men diagnosed with stage T3 comparing initial radiation treatment to prostatectomy plus salvage radiation. While we wait for those results, we have to rely on retrospective studies. In many of the studies cited above, about a quarter of the patients received salvage/adjuvant RT following surgery. In the Mayo study, 72% were recurrence-free after 20 years, which does bring the combination close to what radiation alone often delivers. However, that comes at a cost. Adjuvant and salvage RT usually has worse quality-of-life outcomes than the patient would have suffered had he had radiation to begin with.

This brings us to the second alarming trend: adjuvant and early salvage RT rates have been declining among men with adverse pathology after prostatectomy. We discussed this previously (see this link). So not only are T3 patients receiving a therapy upfront that is less likely to control their cancer, they also may not be receiving the adjuvant or salvage RT that might control it if used early enough.

It is especially troubling that there has been no corresponding shift to later salvage RT. Sineshaw et al. conjecture as to the reasons for the trend:

“This pattern of declining use could be due to multiple factors, including patient preference, physician and referral bias, concern about toxicity, lack of a consistent survival benefit seen in the updated randomized trials, or a growing preference for salvage radiation at time of biochemical failure, rather than immediate adjuvant RT. With respect to the last point, our data did not show a rise in RT use after 6 mo and within the first 5 yr post-RP, suggesting that a shift to salvage RT does not likely entirely explain the declining use of immediate (within 6 mo) postoperative RT.” [emphasis added]

I’d like to believe that the decline in salvage radiation utilization is attributable to better selection of patients. Utilization was higher in those with positive surgical margins and those with Gleason scores 8-10. However, Dr. Sandler may very well be right in attributing the drop-off to urologists who don’t immediately refer patients with adverse pathology to radiation oncologists. In my experience, many patients making the primary therapy decision also never consult with a radiation oncologist. High-risk patients are especially needful of guidance from the first doctor they see – almost always a urologist – to seek second opinions. It would be unconscionable if they are not receiving that guidance.

Hypofractionation – no long-term effect on quality of life

Reducing the number of radiation treatments had no long-term differential effect on urinary, rectal or sexual quality of life, according to a study from Fox Chase Cancer Center that was recently presented at the ASTRO meeting.

These findings compliment their 2013 report of equivalent rates of cancer control from the two treatment schedules. Between 2002 and 2006, they randomly assigned 303 patients to either hypofractionation or conventional fractionation:

• ·      Hypofractionation: 70.2 Gy in 26 fractions (2.7 Gy per fraction)
• ·      Conventional fractionation: 76 Gy in 38 fractions (2.0 Gy per fraction)
• ·      High-risk patients received long-term adjuvant ADT; some intermediate risk patients received short-term ADT (there were no low risk patients).
• ·      Mean age was 67 years in both groups.
• ·      Patients evaluated their quality of life using the EPIC and IPSS questionnaires

The findings that were presented at ASTRO or included in a Medscape article about it were:

• ·      Urinary irritative symptoms declined by less than the amount considered to be minimally clinically detectable at both 3 years and 5 years, and were not different between the two groups.
• ·      Urinary continence symptoms declined by 7% at 3 years and by 9% at 5 years in the hypofractionated group. Compared to the conventionally fractionated group, it was significantly different at 3 years but not significantly different at 5 years. (The EPIC categories that are lumped together as “urinary incontinence” may not mean what most people mean by the term. It may include patient perception of any leaking or dribbling, as well as any pad use. The decline was large enough to be noticeable, but were not very large. The fact that they were not significantly different between the two groups at 5 years may speak to common age-related declines.)
• ·      Patients with poor baseline genitourinary function had worse quality of life outcomes with hypofractionated radiation than with conventionally fractionated radiation
• ·      Bowel symptoms declined by less than the amount considered to be minimally clinically detectable at both 3 years and 5 years, and were not different between the two groups.
• ·      Sexual function declined by a clinically detectable degree at both 3 years and 5 years, but was not different between the two groups.
• ·      Baseline function was an important predictor of long-term quality of life outcomes.

These findings echo the results just reported in the CHHiP trial in the UK. While caution is warranted among men with poor baseline urinary, rectal and sexual function, these two studies provide strong Level 1 evidence that hypofractionated radiation is not inferior to conventionally fractionated radiation. Most patients should be able to complete primary IMRT treatments in about 5 weeks rather than 8 weeks, and at considerably reduced cost.