1. What happens if a man has already had a flow test done prior to when I approach him about UPSTREAM? Can he be considered, and if so, is another flow test required for the purpose of the study?

Approaching men that have already had a flow test is absolutely fine; a flow test recorded up to 6 months prior to the date of informed consent is acceptable and you would not need to repeat another flow post-randomisation unless the doctor would prefer another. Similarly it is not mandatory for men to have had a flow test prior to randomisation. Remember, UPSTREAM is a trial evaluating the diagnostic pathway of men with bothersome LUTS, and flows form part of this pathway.

We do advise, however, that staff do not look at the flow results before approaching men for the study, as that should be done when the doctor is making the treatment decision (i.e. at the end of the diagnostic pathway). Some centres have incorrectly excluded patients based on flow tests. 

2. Can we invite patients who have previously had urodynamics, or are they automatically excluded?

Men who previously had urodynamics can be included in the trial if the urodynamics was not within the past 12 months (from date of possible consent). 

3. Do centre staff need to undertake a specified urodynamics training course prior to taking part in UPSTREAM? Are there certain standards required for the purpose of the study?

There is no expectation that centre staff must do a specified course; we’re assuming each unit trains staff. We do request a copy of the urodynamics traces for each relevant participant and plan to check practice is compatible with ICS standards. For further details, please refer to the Protocol (v4, 29.09.16; page 21) and the UPSTREAM Monitoring Plan (page 7). 

4. Do the operations for UPSTREAM participants need to be done by certain surgeons (i.e. those registered with the trial)?

No; as UPSTREAM is a pragmatic trial, surgery should be done according to local, usual practice. 

5. Does having a flexi as part of the diagnostic pathway make a difference?  I am hoping to offer TURP, PAE, Urolift and HoLEP in due course and for various reasons think a flexi (done by the eventual operating surgeon) would help to select the most appropriate treatment option for each patient. Some may get one if concern about marked storage LUTS in a smoker or haematuria too obviously. 

No problem, we would rank flexi as a “discretionary test”; we ask that this data be captured in the baseline CRF. We are not specifying treatment modality, nor type of surgery (if that is what treatment turns out to be); we are just expecting practice will be in line with NICE/relevant guidelines, and will be done to adequate standard to relieve obstruction (checked with a flow test after ~4 months (+/- 1 month). 

6. Does the eventual treatment modality matter? As mentioned in point 5, some may choose Urolift or HoLEP; will that matter? 

No, please see response to point 5.

The treatment decision is between the urologist and the patient and there are no treatment ‘requirements’ imposed by the UPSTREAM study.

7. I have been presented with a patient that has mixed symptoms.  He seems to be able to only pass small amounts (<150 mls vv) with variable residuals. I notice that this is not exclusionary in terms of the protocol, but you are requesting > 150mls vv for flow rate in the baseline CRF.  

I would appreciate some advice on the best way forward with this situation.

Most units try to check flow tests with a minimum voided volume, commonly 150 mls. However, for some men this proves difficult, either because the largest volume they ever manage is small, or because the circumstances of the flow test influence their urinary behaviour. We have to accept what the gentleman manages on the day; it will be fine to invite this patient in the example given.

8. If prostate cancer is identified at the time of surgery, can the patient remain in the study (given they have gone through the diagnostic pathway), or should they be withdrawn?

Newly diagnosed prostate cancer at the time of surgery; they can remain in study, and it will be a useful secondary outcome of the UPSTREAM study to be able to assess the incidence of previously undiagnosed prostate cancer. It will be appropriate to keep the patient in the study. It will be important to record the management of the prostate cancer (e.g. watchful waiting, radiotherapy or radical prostatectomy), as this will alter the urinary behaviour of the patient. We suggest if such a situation arises you inform us to review on an individual basis.

9. One of the exclusion criteria listed in the protocol is "Men will not be invited to participate is they are unable to pass urine without a catheter (urinary retention)."

What about men who use clean intermittent self catheterisation (CISC)?

CISC is acceptable in situations where it is used occasionally to drain a post void residue. However, entire reliance on CISC for all bladder emptying, or use of CISC to dilate a urethral stricture is not acceptable. Happy to review on an individual basis, so contact us if in doubt.