Questions to ask an SBRT doctor

SBRT doctor questions

1.     How many have you performed?

2.    How has your practice of SBRT changed over the years?

3.    What is your 5-yr freedom from recurrence rate for patients at my risk level? What proportion of your recurrences were local-only?

4.    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?

5.     What is your rate of serious (Grade 3) adverse events? Do you see urinary strictures? Urinary retention requiring catheterization? Fistulas? Rectal bleeding requiring argon plasma or other interventions?

6.    What is the margin you will treat around the prostate? Is it less on the rectal side?

7.     What is the prescribed dose to the planned target volume?

8.    Do you work off a fused MRI/CT scan?

9.    What machine do you use (e.g., VMAT, CyberKnife, step-and-shoot, Tomotherapy, etc.)?

·      If CyberKnife: Do you use the IRIS or a new multileaf collimator?

·      Do you set a limit on “hot spots”?

10.  Do you use fiducials or Calypso transponders? Do you do transperineal placement of them?

o   What system do you use for inter-fractional tracking?

o   What system do you use for intra-fractional tracking?

11.   In my treatment plan, what do you identify as “organs at risk” and what dose constraints do you put on them?

o   What dose will my penile bulb receive?

12.  How long does each treatment take?

13.  How will I be immobilized during each treatment?

14.  Are there any bowel prep or dietary requirements?

15.  Should I avoid taking antioxidant supplements during treatment?

16.  In your practice, among men who were fully potent, what percent remained fully potent 3-5 years later?

o   Have any men retained some ability to produce semen?

o   What is your opinion of taking Viagra preventatively?

17.  Do you monitor side effects with the EPIC questionnaire?

o   In your practice, what percent of men experience acute urinary side effects?

o   In your practice, what percent of men experience acute rectal side effects?

o   In your practice, what percent of men experience late term urinary side effects?

o   In your practice, what percent of men experience late term rectal side effects?

18.  What kind of PSA pattern should I expect following treatment?

19.  What is the median PSA nadir you are seeing in your practice, and how long does it take to reach that, on the average?

20. In your practice, what percent of men experience biochemical recurrence?

o   What % of those have been local?

o   If there should be a biochemical (PSA) recurrence, what would the next steps be?

o   Have you ever used SBRT, brachy, or cryo for salvage after a local SBRT failure, and was that focal or whole gland?

21.  Are you open to email communications between us?

Record 10-year SBRT study among low risk patients

Alan Katz has now published the study with the longest-running follow-up of any study of external beam radiation therapy for prostate cancer among low risk patients, in this case, using SBRT. 10-year follow-up among intermediate and high-risk patients will be presented at next year's ASTRO meeting. This study ties in longest length of follow-up with the Memorial Sloan Kettering (MSK) study of IMRT. IMRT involves 40-45 radiation treatments over the course of about 9 weeks; SBRT shortens the number of treatments to 4 or 5 over the course of about 11 days.

Focusing on their low risk cohort only, the Katz study has a distinct advantage over the MSK study in sample size:

• The Katz study started with 230 low risk patients and, because of later start dates and some loss to follow-up, had 57 evaluable low-risk patients who were tracked for 10 years.
• The MSK study started with 49 low risk patients and, because of later start dates and loss to follow-up, ended with only 2 patients tracked for 10 years.
• Median follow-up was 108 months for Katz and 99 months for MSK

The IMRT study used a prescribed dose of 81 Gy in 45 fractions. The Katz study used a dose of 35 Gy in 5 fractions on 42 patients and 36.25 Gy in 5 fractions on 188 patients (average = 36 Gy). The biologically effective dose for cancer control was 17% higher in the Katz study.

It is risky to compare SBRT and IMRT when patients are not randomized to treatment with one or the other. There has been such a randomized trial, and partial results have been reported (see this link). The median age was the same in both studies (69 years of age), and the same definitions for the low risk category, and for biochemical failure were used. To highlight some of the differences and similarities in outcome:

• 10-year biochemical disease-free survival was 94% for Katz vs. 81% for MSK
• 10-year distant metastasis free-survival was 98.4% for Katz and 100% for MSK
• No prostate cancer-related deaths at 10 years in either study

Late-term urinary and rectal side effects were infrequent and mild in both studies:

• Late-term urinary side effects:
• Grade 2: 9%, Grade 3: 3% in the Katz study
• Grade 2: 9%, Grade 3: 5% in the MSK study
• Late-term rectal side effects:
• Grade 2: 4%, Grade 3: 0% in the Katz study
• Grade 2: 2%, Grade 3: 1% in the MSK study

Of those who were previously potent before radiation, 56% were potent (sufficient for intercourse) 10 years later (median age 79) in both studies.

Other interesting outcomes of the Katz study included:

• Median PSA fell to 0.1 ng/ml after a median of 48 months
• 21% experienced a PSA bounce along the way.
• Cure rates were independent of whether patients received 35 Gy or 36.25 Gy
• Urinary toxicity was higher in the group that got the higher dose
• Rectal toxicity was no different in the two groups
• Patient-evaluated urinary and rectal function declined acutely but returned to baseline within a year
• Sexual function declined by 23% at 6-12 months, and continued to decline by 38% by 8 years. It is unknown what percent of that decline was age related (but see this link).

Looking at the higher local control rates of SBRT and HDR brachytherapy, Dr. Katz sees evidence that IMRT is sub-optimal in delivering biological effective dose. He also believes that no more than 35 Gy in 5 fractions is necessary to achieve that control, and that it would minimize side effects.

Of course, probably half of the low risk men in this study might have gone those ten years without needing any kind of treatment at all. But for those who may not want or may not be good candidates for active surveillance, SBRT is a low cost, low bother, low side-effect alternative that delivers high rates of long-term oncological control.

Amazingly, I still hear that there are insurance companies that will not cover SBRT because longer follow-up is needed. Dr. Katz had already reported the nine-year follow-up (see this link), and with this addition and the 10-year higher-risk update at ASTRO next year, it's hard to see what any objection might be.

Dr. Katz is to be congratulated for continuing to update his study for 10 years. It is a lot of work to follow up with so many patients, and collect and tabulate their reported outcomes. He is a radiation oncologist not associated with a large tertiary care facility that might have more resources at its disposal.

SBRT Dose Escalation

Is there an optimum treatment dose for SBRT? At the low end of the spectrum, Alan Katz found that 35Gy in 5 fractions gave equivalent oncological outcomes with less toxicity compared to 36.5 Gy. At the other end of the dose spectrum, a clinical trial pushed the dose as high as 50 Gy in 5 fractions with disastrous consequences (see this link).  A trial of high dose rate brachytherapy, which is radiologically similar to SBRT, failed to find an optimum dose.

But radiation safety is not only just about dose. We saw that two treatment schedules using the same prescribed dose (40 Gy in 5 fractions) had disparate toxicity outcomes (see this link). In fact, the 12 month toxicity outcomes of Dr. King's high-risk study were recently presented and look excellent (see this link). It's also worth noting once again the outcomes of the 5-year multi-institutional SBRT clinical trial that used 40 Gy in 5 fractions and had excellent oncological and toxicity outcomes (see this link).

Helou et al. reported the outcomes of their SBRT (they call it SABR, but it's the same thing) trials at the Sunnybrook Health Sciences Centre in Toronto, Canada. There were sequential trials conducted from 2006-2014:

• 35 Gy/5 fractions/29 days - 82 low risk men only
• 40 Gy/5 fractions/11 days or 29 days - 177 low and intermediate risk men

A few (12) men had up to 6 months of androgen deprivation to shrink their prostates prior to radiation.

As an early measure of oncological effectiveness, they used PSA at 3 years (PSA3Y) after radiation. After correcting for the other variables like age, baseline PSA, T stage, and ADT use, the dose received remained the biggest predictor of PSA3Y. Median PSA3Y was:

• 0.64 ng/ml in those who received 35 Gy
• 0.27 ng/ml in those who received 40 Gy
• The difference was significant in both low risk men and intermediate risk men

The use of PSA3Y as a surrogate endpoint for biochemical recurrence is controversial. Because prostate cancer progresses very slowly and radiation, at the very least, reduces the cancer burden, it can take at least 5 years, and as long as 10 years, before we start to see concrete evidence that such therapy is curative. Also, a longer time until the nadir is achieved has been found to be correlated with failure-free survival (see this link). Nadir PSA has been proven to be a strong predictor of a lasting cure (see this link), but no one can tell when the nadir will be reached. In a recent study comparing the PSA at 1000 days after SBRT or HDR brachytherapy to the PSA at 1000 days after conventional IMRT, Kishan et al. reported that the PSA was lower for SBRT/HDR-BT. While the downward slope was about the same for the first 1000 days, the slope was steeper afterwards for SBRT/HDR-BT, indicating that a lower nadir would be achieved.

After correcting for confounders like age, baseline urinary function, and time between treatments, late term urinary toxicity of grade 2 or higher was 17 times greater among those who received 40 Gy compared to those who received 35 Gy.

The authors previously reported late term rectal toxicity. After 2 years, the cumulative probability of  grade 2 or higher rectal toxicity was suffered among:

• 5% of the men who received 35 Gy with 4mm margins
• 27% of the men who received 40 Gy with 5 mm margins
• 42% of the men who received 40 Gy with 5 mm margins +  30 Gy to seminal vesicles received 

Grade 3 and 4 rectal toxicity was especially high (10%) in the group that had their seminal vesicles irradiated. There were 3 cases of fistulas that may be attributable to rectal biopsies. [Patients should be very careful about the use of any kind of instrumentation within at least 6 months of radiation. That includes cystoscopies and colonoscopies.] Since this study, the authors have changed their radiation planning to include faster (VMAT) linacs and improved rectal dose constraints. Other changes that might mitigate rectal toxicity may include use of intrafractional tracking, rectal immobilization, and a rectal spacer.

There was clearly a trade-off between SBRT dose and late-term side effects of treatments. Perhaps we will one day be able to identify those cancers that are curable with a lower dose, and treat only those with the more radio-resistant cancers with a higher dose. Some believe that such techniques as simultaneous integrated boosts or heterogeneous planning may cure the cancer in the prostate better with less damage to organs at risk. But they remain to be proved in randomized clinical trials.

Note: Thanks to Dr. Andrew Loblaw for allowing me to review the full text of the study.

SBRT for High Risk Prostate Cancer (update)

One of the more interesting developments in the use of radiation to cure high risk prostate cancer is to use SBRT (see this link). The standard of care remains external beam radiation with a brachytherapy boost. But SBRT, if successful for this purpose, may afford equal oncological outcomes with less toxicity and completion in only 5 treatments.

(update 11/18/2018) Alayed et al. reported the 5-year outcomes of 60 men treated with SBRT (which they call SABR) for high-risk prostate cancer at Sunnybrook Hospital in Toronto. The prospective pilot trial comprised 2 cohorts of 30 men each, treated as follows:

1. 40 Gy in 5 fractions to the prostate + 30 Gy in 5 fractions to the seminal vesicles
2. 40 Gy in 5 fractions to the prostate + 25 Gy in 5 fractions to the seminal vesicles AND the pelvic lymph nodes

12-18 months of adjuvant ADT were used in both groups.

Median follow-up was 5.6 years for Group 1 and 4.0 years for Group 2. The 5-year outcomes were:

• Biochemical failure was 15% in Group 1 and 0% in Group 2
• 4-year PSA was < 0.4 ng/ml for 63% of Group 1 and 93% of Group 2
• Late sexual and rectal side effects were worse for Group 1 than Group 2, urinary side effects were similar

This suggests that SBRT provides oncological outcomes that are similar to brachy boost therapy, while the side effects may be lower, especially if the dose to the seminal vesicles is 25 Gy/ 5 fractions. It also suggests that whole pelvic treatment is probably beneficial in high-risk patients and that toxicity is not higher.


Katz and Kang have presented the largest and longest follow-up trial of SBRT for high risk patients, with 98 patients and 8 years of follow up. Of those, 46 were treated with an SBRT boost following whole pelvic IMRT radiation, and 52 were treated with SBRT monotherapy. The 8-yr biochemical disease-free survival was 61%. This did not differ significantly whether they received the SBRT boost or monotherapy. It also did not differ significantly whether they received adjuvant ADT (55% did). Several different doses were used, but none had significantly better performance. Higher stage and higher grade cancers were cured equally well. Only patients with high initial PSA, perhaps indicative of metastases, fared worse than patients with lower initial PSA. Late Grade 2 rectal toxicity was higher for the combo IMRT+SBRT treatment. Late urinary and rectal toxicity were low (5% grade 2 + 3% grade 3 urinary, 7% grade 2 bowel toxicity), and transient, with none after two years.  This was reflected in patient-reported quality-of-life scores, which declined immediately after treatment but returned to baseline in less than a year.

Kishan et al. presented early toxicity outcomes of the UCLA SBRT trial for high risk patients, which was described here and here. They treated 61 patients, 40 with adjuvant androgen deprivation therapy, 23 also received radiation to the pelvic lymph nodes. ADT and nodal radiation had no effect on toxicity.

After 1 year of median follow-up, the physician-reported toxicities were as follows:

• There were no grade 3 or higher toxicities
• Acute grade 2 urinary toxicity - 13%
• Acute grade 2 rectal toxicity - 7%
• Late grade 2 urinary toxicity  - 7%
• Late grade 2 rectal toxicity - 8%

At 12 months, the percent of patients who reported at least minimally detectable changes were:

• Urinary incontinence: 14%
• Urinary obstructive symptoms: 31%
• Bowel symptoms: 28%

There is also a recent report on SBRT boost therapy for high risk patients (see this link). Paydar et al. reported on 108 patients treated at Georgetown University,  59 of whom were high risk. The toxicities reported were as follows:

• Acute urinary toxicity - 18% grade 2 ,  1% grade 3
• Acute rectal toxicity - 7% grade 2
• Late urinary toxicity  - 40% grade 2, 6% grade 3
• Late rectal toxicity - 12% grade 2, 1% grade 3

SBRT boost therapy seems to increase toxicity significantly more than SBRT monotherapy. We will have to wait for reports of oncological outcomes to see whether the trade-off is worthwhile.

Less treatment regret with SBRT and when patients are fully informed at UCLA

There is growing recognition that the patient's satisfaction or regret with his treatment decision is more than just a matter of whether he is happy with the oncological outcome. Satisfaction/regret is the product of many variables, including how well he understood his options, his interactions with his doctors, the side effects he suffered and when he suffered them, his expectations about the side effects of treatment, and cultural factors.

Shaverdian et al. explored the issue of treatment regret with patients treated at UCLA with three kinds of radiation therapy: Intensity Modulated Radiation Therapy (IMRT), Stereotactic Body Radiation Therapy (SBRT), and High Dose Rate Brachytherapy (HDR). Questionnaires were sent to 329 consecutive low or favorable intermediate risk patients treated from 2008 to 2014 with at least one year of post-treatment follow-up. There was a high (86%) response rate. The number of responses were:

• IMRT -  74 patients
• SBRT - 108 patients
• HDR  -   94 patients

Patient characteristics were similar across treatments. The only significant differences were:

• HDR patients were a median of 5 years younger
• IMRT patients disproportionately African- American and Asian-American
• Length of follow-up was longer for IMRT patients
• HDR patients were more likely to be taking medication for erectile dysfunction.

Decision-making process

Those that chose IMRT spent less time making their decision. The percent that spent less than a month making their decision was:

• IMRT: 47%
• SBRT: 31%
• HDR:  12%

Although most patients felt they had learned enough about the treatment options before making their decision, those who chose IMRT were least likely to say so:

• IMRT: 83%
• SBRT: 91%
• HDR: 86%
• 11% of the IMRT patients wished they had learned more about active surveillance.

There was widespread agreement that they had worked mutually with their doctors to arrive at a decision.

• IMRT: 85%
• SBRT: 91%
• HDR: 84%

Treatment regret

The percent who felt that they would have been better off with a different choice was least for SBRT:

• IMRT: 19%
• SBRT: 5%
• HDR: 18%
• This rate of treatment regret for IMRT and HDR is similar to the rate expressed for surgery (see this link).

Of those who expressed treatment regret, the biggest reason for it (36%) was because they could have had better sexual function. 72% of those with treatment regret would have chosen active surveillance if they had it to do over again.

 
After correcting for patient characteristics, the factor most associated with treatment regret was whether they had learned enough about other treatments. Those with treatment regret were 53 times as likely (odds ratio) to say that they had not learned enough. The next biggest factor predicting treatment regret was whether the long-term side effects were worse than expected (odds ratio = 42). Expectations and the disappointment of those expectations have a large impact on treatment regret. Those who chose IMRT were 11 times more likely to have treatment regret than those who chose SBRT, and those choosing HDR were 7 times more likely to experience treatment regret compared to SBRT. The table below shows the odds ratio for all statistically significant factors.

	Relative impact on treatment regret  (odds ratio)
Decision-Making Factors
Learned enough about treatments	53
Mutually worked with physicians	16
Doctors fully informed me	11
Side Effects
Short-term side effects worse than expected	8
Long-term side effects worse than expected	42
Bowel function	8
Sexual function	5
Urinary function	5
Treatment
IMRT vs SBRT	11
HDR vs SBRT	7
HDR vs IMRT	1

While IMRT was the highest cost treatment, it also gave the lowest value to the patient. Conversely, SBRT, the lowest cost treatment, provided patients with the highest value. To increase value to patients, doctors must assure that patients are fully informed about all their treatment options, and the side effects that they may reasonably expect. Patients should be encouraged to take their time investigating options, especially active surveillance.

All patients in this study were treated at UCLA, which has a policy of fully informing patients of all their options and expected outcomes. It is impossible to entirely separate the effect of superior patient counseling on the part of the physician from the superior treatment outcomes as the reasons for increased patient satisfaction. Perhaps if this questionnaire were used across multiple institutions those effects could be distinguished. Because UCLA is a nationally-renowned tertiary care center, these results are not at all applicable to what goes on in the community setting. If expanded, we would like to see comparisons with other treatment modalities: surgery (robotic and open), low dose rate brachytherapy, active surveillance, proton beam therapy, hypofractionated IMRT, and focal ablation therapies. It would also be instructive to compare the value attached to adjuvant treatment modalities (e.g., brachy boost therapy and hormone therapy) given to patients with more advanced disease and in the salvage setting. It is a good start, however, and provides a validated questionnaire by which treatment centers can assess their performance and set goals for improvement. We would love to see this "report card" expanded nationally.

Questionnaire

For those who have been treated and would like to see how your treatment falls on the treatment regret questionnaire, I've copied it below. It may also be useful for those who have not yet been treated to help assure you minimize your treatment regret.

Prostate Cancer Patient Voice Questionnaire

This questionnaire is designed to better evaluate your treatment experience so that we can continue to improve the quality of the care we provide. To help us get the most accurate measurement, it is important that you answer all questions honestly and completely.

Name: _______________________________________

Today’s Date (please enter date when survey completed): Month ________ Day_______ Year________

Question 1:
What is the highest level of education you have received? 
a) Less than high school
b) Graduated from high school
c) Some college
d) Graduated from college 
e) Postgraduate degree

Question 2:
How much time did you think about your diagnosis and treatment options before deciding on your treatment?
a) Less than 1 month 
b) 1-2 months
c) 2-4 months
d) 4-6 months
e) Over 6 months

Question 3:
Do you believe you learned enough about the different treatment approaches for treating prostate cancer before undergoing treatment? (circle all that apply)

1. a)  Yes
   
2. b)  No, I wish I had learned more about intensity
   modulated radiation therapy (IMRT)
   
3. c)  No, I wish I had learned more about stereotactic body
   radiation therapy (SBRT)
   
4. d)  No, I wish I had learned more about brachytherapy
5. e)No, I wish I had learned more about active surveillance
6. f) No, I wish I had learned more about surgical treatments
7. g) Other (please specify): _______________________ ___________________________________________

Question 4:
How true or false has the following statement been for you? “I felt that I worked with my doctors to mutually decide on the best treatment plan for me.”
a) Definitely false
b) Mostly false
c) Neither true nor false 
d) Mostly true
e) Definitely true

Question 5:
During the past 4 weeks, how much of the time have you wished you could change your mind about the kind of treatment you chose for your prostate cancer? 
a) None of the time 
b) A little of the time 
c) Some of the time 
d) A good bit of time 
e) Most of the time

f) All of the time

Question 6:
How true or false has the following statement been for you during the past 4 weeks?
“I feel that I would be better off if I had chosen another treatment for my prostate cancer.”
a) Definitely false
b) Mostly false
c) Neither true nor false 
d) Mostly true
e) Definitely true

Question 7:
If you do have regret about your treatment, which one of the following most accurately describes the reason why you have regret?

1. a)  I could have had fewer urinary symptoms with another treatment.
   
2. b)  I could have had fewer rectal symptoms with another treatment.
   
3. c)  I could have had better sexual function with another treatment.
   
4. d)  I could have had a less costly treatment.
   
5. e)  I could have had another more effective treatment.
   
6. f)  I could be better off now without having had any active treatment.
   
7. g)  Other (please specify): _______________________ ___________________________________________
   

Question 8:
If you do have regret about your treatment, which one of the following most accurately describes the treatment you now wished you had received?

1. a)  I would rather have had surgery (robotic or open prostatectomy).
   
2. b)  I would rather have had stereotactic body radiation therapy (SBRT).
   
3. c)  I would rather have had Brachytherapy.
   
4. d)  I would rather have had Intensity Modulated Radiation Therapy (IMRT).
5. e) I would rather have gone forward without active treatment (Active Surveillance).
6. f) Other (please specify):__________________________________________________________________

Question 9: 
This question asks about the short-term side effects. While undergoing treatment, were the short-term side effects you actually experienced less than or more than you had originally expected?
a) The side effects I actually experienced were exactly as I had expected.
b) The side effects I actually experienced were significantly less than I had expected. 
c) The side effects I actually experienced were slightly less than I had expected.
d)  The side effects I actually experienced were slightly more than I had expected.
e)  The side effects I actually experienced were significantly more than I had expected.

Question 10: 
This question asks about the long-term side effects. After completing treatment, were the long-term side effects you actually experienced less than or more than you had originally expected?

1. a)  The side effects I actually experienced were exactly as I had expected.
   
2. b)  The side effects I actually experienced were significantly less than I had expected.
   
3. c)  The side effects I actually experienced were slightly less than I had expected.
   
4. d)  The side effects I actually experienced were slightly more than I had expected.
   
5. e)  The side effects I actually experienced were significantly more than I had expected.
   

Question 11:
How strongly do you agree or disagree with the following statement? 

“Based on my experience, I believe my doctors fully informed me about possible side effects before I started treatment.”
a) Strongly disagree
b) Disagree
c) Neither agree nor disagree 
d) Agree
e) Strongly agree

Question 12:
Overall, how big a problem have your urinary, bowel, and sexual functions been for you during the last 4 weeks? (circle one number on each line) 

             (0) No problem  (1)Very small problem (2)Small problem  (3)Moderate problem (4)Very big problem 
Urinary function  0 1 2 3 4 
Bowel function    0 1 2 3 4 
Sexual  function   0 1 2 3 4 

note: Thanks to Dr. King for allowing me to review the full text.