Wednesday, December 27, 2017

Is ADT still needed for high risk patients receiving brachy boost therapy?

Brachy boost therapy (external beam plus a brachytherapy boost to the prostate) is the gold standard for high risk patients, reporting the best oncological outcomes of any therapy. While long-term adjuvant ADT has proven to be beneficial in prolonging survival in high risk patients when used in conjunction with dose-escalated external beam radiation (DART 01/05 GICOR), there has never been a randomized trial to determine if there is any benefit to ADT when used with brachy boost therapy.

All we have to go by are several single or multi-institutional studies and one large database analysis. Almost all of the studies so far show no effect to short-term (4 months, starting 2 months prior and running concurrent with the radiation therapy) adjuvant ADT.

Two of the studies used a boost of low dose rate brachytherapy, predominantly using Pd-103 seeds. Dattoli et al.  found there was no significant difference in 16-year PSA progression-free survival (PSA-PFS) whether 4 months of ADT were added or not. D'Amico et al. also found no significant difference in 8-year prostate cancer specific mortality (PCSM) with the addition of ADT. However, they felt that it was "approaching significance" (p=.08) and might become statistically significant with longer follow-up. In contrast to the Dattoli study, the D'Amico study did not treat the pelvic lymph nodes.

A recent analysis of the large National Cancer Database by Yang et al. did not detect any benefit to adding ADT on 8-year overall survival (OS). The database lacks specific information about type of brachytherapy, radiation doses, duration of ADT, and whole-pelvic treatment,

Several studies that used high dose rate brachytherapy as a boost also looked at this issue retrospectively. Demanes et al. was the earliest of those studies. They found no difference in 10-year PSA-PFS in their 113 high risk patients treated between 1991-1998. Several subsequent studies confirmed those findings. Galalae et al. concatenated the databases from 3 institutions: Kiel University, University of Washington Seattle and William Beaumont Hospital. Short-term adjuvant ADT failed to demonstrate improved 10-year PSA-PFS in the 359 high risk patients treated between 1986 and 2000. And the lack of effect was demonstrated at all three institutions. Kotecha et al. also failed to find any differential improvement in 5-year PSA-PFS among 61 high risk patients treated with HDR brachy boost at Memorial Sloan Kettering between 1998 and 2009.

There has been one "outlier" study. Schiffmann et al. reported on 211 consecutive high-risk patients treated at the University Medical Center Hamburg-Eppendorf from 1999 to 2009. After 10 years, the biochemical recurrence-free survival was 50% with the adjuvant ADT but only 39% without it - a very statistically significant and meaningful difference. However, even the "improved" outcome seems low compared to the ASCENDE-RT trial where everyone got early neoadjuvant and adjuvant ADT. In that trial, the 9-year PSA-RFS for high risk patients receiving the trimodality therapy was 83%. Another multi-institutional study of HDR-brachy boost therapy reported 10-year PSA PFS of 85% with ADT and 81% without ADT in high risk patients. It is plausible that the patients in the Hamburg study had more advanced disease and had more undetected micrometastases compared to the other studies.

The following table summarizes the treatments given in the aforementioned studies, and whether there was a statistically significant improvement (p<.05).




Relative BED is the biologically effective radiation dose as a percent of the BED of 79.4 Gy of IMRT in 44 fractions.


Short-term vs. Long-term Adjuvant ADT

ADT is believed to have two effects when used in conjunction with radiation. Used before radiation begins (neoadjuvant use) and during radiation treatments (concurrent use), it radio-sensitizes the cancer. Lab findings suggest that it interferes with cancer cell repair of the induced DNA double-strand breaks. Used after radiation (adjuvant use), ADT is believed to "clean up" any remaining local micrometastases that survived. The death of cancer cells from both the radiation and the ADT dumps antigens into the serum that may activate T-cells. Those T-cells may hunt out and destroy small amounts of cancer cells nearby (the bystander effect) or systemically (the abscopal effect).

The bulk of the above retrospective studies suggest that the radiosensitizing effect is unnecessary with the very high radiation doses given with brachy boost therapy. However, what remains to be shown is whether long-term ADT might confer any additional benefit. The DART 01/05 GICOR trial proved that there was a significant benefit to 28 months of ADT compared to 4 months in high risk patients treated with dose-escalated EBRT. It is possible that while short-term ADT may have no benefit, long-term ADT combined with brachy boost therapy might.

TROG 03.04 RADAR was an Australian randomized trial that was designed to detect whether Zometa and longer duration of ADT (18 months vs 6 months) could provide better cures when combined with varying doses of radiation (radiation dose received was stratified but not randomized). Some of the patients received brachy boost therapy. In general, it found that higher radiation doses combined with longer duration of ADT provided the best outcomes. However, among those patients who received HDR brachy boost therapy, there was no significant difference in progression (fig.2 - showing overlapping standard error bars) whether they received 18 months or 6 months of ADT.

The very high rates of cancer control (around 80%-85%) using brachy boost therapy may be as high as we can reasonably hope for, given that there will always be some patients with undetected occult micrometastases.

Better patient selection

High-risk patients are usually given a bone scan and CT to help rule out distant metastases. Bone scans are non-specific to prostate cancer and are not very sensitive when the PSA is below 20 ng/ml. CT scans detect metastases larger than about 1.2 cm, but most metastases are smaller than that. The newly-approved Axumin PET scan, and the experimental PSMA-based PET scans now in clinical trials may be able to detect those distant metastases earlier. However, there are currently no PET scans approved for high-risk patients outside of clinical trials (they are only approved for recurrent and advanced cancer patients). In the future, those high-risk men in whom metastases have been detected via PET scans may be better candidates for systemic therapies, while those in whom no metastases have been detected may be better candidates for brachy boost therapy. It may be economically justifiable to use PET scans for this purpose. Perhaps we will see another 5-10% increase in cancer control rates, even without ADT, with better patient selection. A recent analysis of recurrent patients after prostatectomy diagnosed using the Ga-68-PSMA PET/CT found that 12% had previously undetected metastases outside of the radiation treatment field.

Dose Escalation

At the high biologically effective doses (BEDs) used in all the brachy boost studies, there does not seem to be a significant interaction between dose used and whether ADT was effective. The Dattoli study had the lowest BED, but no benefit to added ADT, while the Galalae study had the highest BED, but also no benefit to added ADT. The Hamburg study had high BED but did demonstrate a benefit to added ADT. All of the brachy boost studies seem to have adequate radiation doses.

Whole Pelvic Radiation

It is possible that pelvic lymph nodes are best treated with a combination of radiation and ADT.  Bittner et al. looked at 186 high risk patients treated with the brachy boost  therapy. The 10-year PSA-PFS was:

  • 94% if they received both whole pelvic radiation and ADT
  • 82% if the received whole pelvic radiation without ADT
  • 90% if they received ADT without whole pelvic radiation
  • 75% if they received neither ADT nor whole pelvic radiation


ADT seemed to have a bigger effect than whole pelvic radiation. This may be because the whole pelvic radiation dose is inadequate. The doses given to the pelvic lymph nodes are quite a bit lower (about 50 Gy in 28 fractions) than the dose to the prostate. If Dr. King is right that prostate cancer is inherently radioresistant and requires a higher lethal dose (about 79.2 Gy/44 fx) to be effective, even when the cancer is only in the prostate bed (see this link), it is possible that pelvic lymph nodes require a higher dose as well. Because of the potential bowel toxicity of escalated pelvic doses, adjuvant ADT may be necessary to achieve effective cell kill rates without dose-limiting toxicity. We saw in a recent analysis that, in the salvage situation among patients with GS 8-10, whole pelvic radiation and ADT both had significant benefits. Whether whole pelvic radiation is effective in high risk patients treated with brachy boost therapy and ADT is the subject of a major ongoing randomized clinical trial (RTOG 0924).

Retrospective vs Prospective Trials

All of the published studies so far have been retrospective and are therefore subject to selection bias: those who received the ADT had more progressed disease than those who received the brachy boost without ADT. Therefore, it will always be impossible to convincingly resolve this issue without a prospective randomized clinical trial.

Patient decisions

Until we have definitive results from randomized clinical trials, the decision over whether to add ADT to brachy boost therapy will be challenging. Many patients are persuaded by the extra insurance ADT provides, and that only a short course seems to be necessary. Others are so ADT-averse that even a short course is unthinkable, especially with no concrete evidence of efficacy.

The decision over whether to include the whole pelvic area in the external beam radiation field may be an easier decision. High risk patients have a significant probability that there are small metastases harbored in pelvic lymph nodes. Recent studies have shown the treatment field must be wider than  was previously thought. For some patients with anatomical abnormalities, low visceral fat, and a history of bowel disease, this too may present a challenging decision.



Sunday, December 24, 2017

Salvage whole pelvic radiation after cancerous pelvic lymph nodes have been found

Is it still worthwhile to attempt salvage radiation (SRT) after positive pelvic lymph nodes (stage pN1) have been pathologically detected? Traditionally, patients with PLND-diagnosed pN1 prostate cancer have been considered to have incurable systemic disease. Therefore, they were either observed until distant metastases were identified or started on lifelong androgen deprivation. Retrospective studies of the benefit of salvage whole pelvic SRT for pN1 patients have been equivocal: Abdollah et al. and Rusthoven et al. showed a benefit to salvage RT, but Kaplan et al.showed no benefit.

In an analysis of the National Cancer Database of 7,791 prostatectomy patients (treated from 2003-2010) who were staged pN1 after PLND, Zareba et al. found that most (63%) were initially observed without treatment, and an additional 20% received androgen deprivation (ADT)-only within a year of diagnosis. Only 18% received SRT, most of those (72%) with adjuvant ADT. Those treated with whole pelvic SRT+ADT had worse disease characteristics than those who were observed only: higher Gleason score, higher stage, higher positive surgical margin rate, and greater number of positive lymph nodes.

After 5.9 years median follow-up on 3,680 patients:
  • Treatment with whole pelvic SRT+ADT decreased 10-yr mortality by 31% compared to observation only, and by 35% compared to ADT-only.
  • Treatment with ADT-only or SRT-only was not associated with an increase in survival

Touijer et al. reported on 1,388 pN1 patients treated at three top institutions: Memorial Sloan Kettering (MSK), the Mayo Clinic, and San Raffaele Hospital in Milan. The MSK cohort was primarily only observed, the Mayo cohort primarily received lifelong ADT-only, and the Milan cohort was primarily treated with whole pelvic SRT+ADT As in the Zareba study, SRT+ADT patients had worse disease characteristics.

After 5.8 years median follow-up:
  • Treatment with whole pelvic SRT+ADT decreased 10-yr mortality by 59% compared to observation only, and by 54% compared to ADT-only.
  • Those with worse disease characteristics benefited the most.
  • Treatment with ADT-only was not associated with an increase in survival compared to observation, although prostate cancer-specific survival was increased.

None of these studies reported the toxicity of the salvage treatment, but with improved external beam radiation techniques and scrupulous image guidance, toxicity has been improving.

These two studies had very similar outcomes. Although they were both retrospective studies rather than prospective randomized trials, it should be noted that the selection bias that typically plagues retrospective studies favored those who did not receive SRT+ADT. In spite of their worse disease characteristics, the patients who received pelvic SRT+ADT survived longer.

Recently we saw a similar advantage to pelvic SRT+ADT even in men who were not diagnosed as stage pN1 with a PLND (see this link). Taken together, these studies indicate a marked survival advantage to treating the whole pelvic area in men with pathologically diagnosed high-risk prostate cancer post-prostatectomy. A previous study found that among men with pN1, the ten-year incidence of distant metastases was 35%, suggesting that spread may be confined to pelvic lymph nodes for some time. This creates a unique window of opportunity during which salvage treatment may still be curative.

We have also seen evidence that high risk patients with imaging-detected positive lymph nodes benefited from whole pelvic radiation as primary therapy (see this link).

These studies also constitute better evidence than we currently have that whole pelvic radiation with ADT is a better idea than picking off lymph nodes one at a time (for which we have no evidence of survival benefit). As we have seen (see this link), our ability to detect all cancer-infected lymph nodes is poor.

There are several variables that the patient and doctor must decide upon, and for which there is no clear evidence: duration of adjuvant ADT, amount of radiation, and the pelvic lymph node field. Clinical trials show that at least 6 months of adjuvant ADT with SRT even without lymph node involvement increases oncological effectiveness, the optimal duration is unknown and may vary with disease characteristics (see this link). The amount of radiation to the pelvic lymph node field seems to be about 50 Gy in most cases, and the amount given simultaneously to the prostate bed will ideally be at least 70 Gy (see this link). The extent of the treated area has been questioned recently. Studies show that infected lymph nodes are often missed in the common iliac area (see this link). There will be variations due to individual anatomy and known bowel sensitivity.

Tuesday, December 19, 2017

Metastasis-Directed Therapy for Oligometastatic Recurrence

Metastasis-directed therapy (MDT) for recurrent oligometastatic prostate cancer is a very controversial topic. Researchers who should know better have made unjustified claims (see this link) and have even posted YouTube videos replete with "gee whiz" cases.

Now we have the first randomized clinical trial on the subject. It's a small trial (62 patients randomized to MDT or Surveillance) and it only ran for three years (not long enough to detect survival differences in early metastatic patients). The objective of the study was not to see if MDT extended survival (which is what we really want to know), but to determine whether it extended the period before salvage ADT was required. The authors believe that if that more modest claim is realized, then a larger, longer Phase 3 randomized trial to detect any survival improvement would be justified.

"Oligometastatic" was defined as 1 to 3 detected metastases. Metastases were detected using a Choline PET/CT scan. Metastases could be in the pelvic lymph nodes (stage N1) or in distant locations (stage M1). Due to the small sample size in this study there was a serious disparity in the number of mets: the MDT group had fewer detected mets (58% had only one met) than the Surveillance group (29% had only one met).

"Recurrent" means after primary prostatectomy or radiation therapy has failed, and in some cases, salvage therapies have failed as well. Primary therapy may have included extended pelvic lymph node dissection (ePLND) with prostatectomy or whole-pelvic radiation along with prostate radiation. In this study, most (76%) had prostatectomy and many of them (85%) had failed salvage radiation.

"Metastasis directed therapy" included spot radiation (SBRT) to detected metastases, or surgical removal of lymph nodes or soft-tissue metastases. In this study, 55% of patients had lymph node mets. If the patient had already had whole pelvic radiation or ePLND and any cancerous pelvic lymph nodes were detected, only those lymph nodes were removed. Otherwise a salvage ePLND was performed. Some patients were treated with SBRT to individual lymph node mets, but none were treated with radiation to the whole pelvic lymph node field. Bone mets were treated with SBRT (in 45% of patients), and one lung met was surgically removed. If mets were detected on follow up in the MDT group, they were treated if there were 3 or fewer (i.e., whack-a-mole).

"ADT-free survival" is the time from randomization to the time ADT was required for any of three reasons: symptomatic progression, progression to more than 3 metastases (called "polymetastatic progression"), or local progression of baseline-detected metastases. PSA progression was not an adequate reason to start ADT. It is well known that MDT will result in a temporary reduction of PSA that is not sustainable. The goal of any therapy is to treat the disease, not to treat the PSA.

After a median follow up of 3 years, Ost et al. reported that:
  • Median ADT-free survival was 8 months longer in the MDT group
    • 21 months  in the MDT group vs. 13 months in the Surveillance group
    • The difference was not statistically significant with 95% confidence, but was within the pre-specified 80% confidence range*
  • 39% had not started ADT in the MDT group vs. 19% in the Surveillance group
  • 61% started ADT for polymetastatic progression (half of them within one year of treatment) in the MDT group vs 55% in the Surveillance group
  • Location of metastases did not affect ADT-free survival
  • There was no significant difference in ADT-free survival (even at 80% confidence) among those who had a PSA doubling time at baseline of >3 months
  • Treatment toxicity was mild
* The authors pre-specified an 80% confidence interval for this pilot study. This is unusual. Ostensibly, this was because they knew they would be implementing an expanded Phase 3 study and only wanted to check for gross differences in this Phase 2 pilot study.  In a more conventional statistical analysis, the hypothesis that MDT affected ADT-free survival would have been rejected. Also, at 80% confidence, they should have accepted the hypothesis that the higher number of mets in the Surveillance group made a difference - but the authors seem to ignore the inconsistency. Because of this, patients and clinicians are cautioned to not make changes in treatment decisions based on this.

Because "polymetastatic progression" was the endpoint used to determine whether ADT was indicated for treatment, and 39% of the Surveillance group were already starting with 3 metastases at baseline, it is surprising that it took 13 months for a single new metastasis to become detectable in that group, and that for 19% of the Surveillance group, a fourth metastasis never became detectable throughout the 3 years of follow up. In the MDT group, four new metastases had to become detectable after the first ones were eradicated by treatment. 31% (11 of 31) had a second round of treatments, and 6% had a third round of treatments before the sudden appearance of four or more detectable metastases all at once. By setting "ADT-free survival" as the endpoint and making it conditional upon the simultaneous detection of four metastases, they guaranteed that the endpoint would be reached earlier in the Surveillance group. What is surprising is that even with that built-in bias, the difference was not significant with 95% confidence. It is also worth noting that in a pre-planned subgroup analysis, there was no significant difference in ADT-free survival (even at 80% confidence) among those who had a PSA doubling time at baseline of >3 months. Patients with "indolent" metastases did not benefit from MDT. This study does not show that metastatic progression was slowed by MDT. Only an improvement in overall survival time can show that.

This study used a Choline PET (F18, I presume) scan to detect metastases. We recently saw that there is a clinical trial at Johns Hopkins to detect and treat oligometastases using the more accurate PSMA PET scan. While outcomes may be improved with a more accurate scan, it will undoubtedly eliminate many patients from the oligometastatic pool of patients.

This study did not investigate whether salvage radiation to the entire pelvic lymph node field would have had better outcomes than spot SBRT treatment. We are still not very good at finding cancerous lymph nodes (see this link) and the treatment field is inadequate most of the time (see this link).

Importantly, this study does not address whether it is beneficial or detrimental to delay start of ADT. The 8-month delay in the start of ADT may result in 8 months that the cancer is systemically multiplying and evolving. The TOAD trial suggested that early amelioration of the micrometastatic burden in recurrent patients may have a greater influence on survival than any selective evolutionary pressure that starting earlier may exert. It furthermore showed that overall quality of life was unaffected by the earlier ADT start. ADT is the standard of care when metastases have been discovered. Clinical trials of oligometastatic MDT should include ADT use in both arms to give a realistic appraisal  and to be ethical.

While this trial was done among recurrent patients, the STAMPEDE trials (see this link and this link), the CHAARTED trial, and the LATITUDE trial among newly-diagnosed patients proved that aggressive systemic therapy, as early as possible after metastases are discovered, provides significant survival advantage.

It is important that patients understand the very real risk of avoiding systemic treatment when there are known metastases. While it risks little to treat those oligometastases that can be safely treated, we must understand that there is no known survival benefit to doing so. There is a known risk to delaying systemic therapy. Dr. Ost wrote to me, "MDT does not replace ADT and our results should not be interpreted in that way."


Tuesday, December 12, 2017

Second opinions

When should I get a second opinion?

In our era of increasing medical specialization, it is sometimes a good idea to get additional medical opinions from experts in specific fields. It is unreasonable to expect any single doctor to know everything. There may be several reasons for seeking a second opinion.

Here are some situations that may lead you to get a second opinion:
• Just a feeling that something doesn’t seem right to you.
• The response to treatment isn’t what you’ve been led to expect
• Your doctor has told you something (or you think he has) that conflicts with information from another doctor or study you’ve read
• You want another opinion regarding a controversial issue (e.g., adjuvant vs salvage radiation, intermittent vs continuous hormone therapy)
• You want to explore a specific new or experimental diagnostic technique or treatment (e.g., CDUS, mpMRI, focal ablation, hyperthermia, etc.)
• You want a more aggressive protocol – something beyond the standard of care.
• You have a rare type of cancer (e.g., neuroendocrine) and want advice from an experienced specialist.
• You want another set of eyes or a confirmation on your biopsy slides, pathology, or radiology results.

The first second opinion we should all get is an expert opinion on our biopsy slides. The pathologist at most hospitals must be a jack of all trades. He has to be able to assess all kinds of tissue samples from cancers as well as all other diseases. Consequently, it would be unreasonable to expect them to be expert at reading a prostate biopsy. It is as much an art as a science, and even practiced pathologists looking at the same slide may differ. Unlike pathology labs in most hospitals, Jonathan Epstein's lab at Johns Hopkins has pathologists who specialize in reading prostate tissue samples. Their opinions are widely held to be definitive. The out-of-pocket cost may be in the $250 range (insurance may not cover it), and it is a simple matter to call your urologist to forward the slides to them. Here is the link.

The other diagnostic technique where a second opinion may change your treatment is multiparametric MRI (mpMRI). There has been a surge in popularity of mpMRIs and they seem to be offered by new facilities everyday. The downside is that these are notoriously difficult to read. Experienced “rockstar” radiologists may score them differently from neophytes, and there is considerable inter-observer variability. If you are confident that a “rockstar” read yours, all well and good. If you got yours at a facility that recently began offering them, you may want the DVD sent to a rockstar for a second opinion.

Color Doppler Ultrasound (CDUS) is another imaging technique where years of training make a difference. There is a dynasty of CDUS readers who have mentored pupils starting with Dr. Lee. He taught Dr. Bahn, who taught Dr. Ukimura. I’ve had the opportunity to watch Dr. Bahn in action, and can attest to the artistry involved.

Who do I get second opinions from?

Many of the same techniques mentioned in the blog  “Finding the right doctor,” may be useful in finding the right doctor for a second opinion. 

One aspect to consider is whether you want an opinion from an unrelated doctor at an unrelated institution. If you are suspicious of something your doctor has told you, you may not want him to recommend the doctor for the second opinion. For example, I spoke to a man who had detectable yet stable PSA after his RP. His pathology Gleason score was 6, negative margins, no EPE or SVI. His urologist recommended salvage radiation, and a second urologist at the same practice who took an MRI concurred. He then went to a large tertiary care facility, and an MRI there revealed a “huge” chunk of prostate tissue left behind – something his first urologist failed to mention on the surgery report, and the second urologist did not mention on the MRI report, only noting a small amount of residual tissue. I don’t mean to imply that most urologists are like those two, but I’m only suggesting that an unrelated second opinion has the imprimatur of impartiality.

I think many tertiary care facilities have “tumor boards” that meet periodically to discuss difficult cases. You may be getting the benefit of some of the great practitioners in the field, and also some “out-of-the-box” thinking from experts in related disciplines. This is one of the advantages to treatment at large tertiary care facilities.

How do I tell my doctor?

Doctor’s are professionals. Approach them with the respect they deserve, and most will respond in kind. I’ve never heard of a doctor objecting to getting a second opinion – they are trained to value them. As long as you don’t take a confrontational stance, he will probably be fine with it. Also, avoid “shopping” until you get the opinion you decided in advance you wanted to hear. Doctors have been known to drop patients for doing that. Just as you expect your doctor to keep an open mind, he has a right to expect the same from you.

Other second opinion issues

• How do I resolve two conflicting opinions from equal experts? 
• Will my insurance cover it?
• What if my doctor won’t follow the second opinion?
• What if I don’t like the second opinion?

Managing the Doctor/Patient Relationship

Being one’s own patient advocate means taking responsibility for one’s own health decisions. This is a quantum change from the way things were not very long ago. My parents were very silent in their meetings with doctors. They trusted the doctor to do what was best for them, even though the doctor could only surmise, based on his subjective point of view and his experience with other patients, what it was my parents’ wanted. This is sometimes called the paternalistic model of doctor/patient relationships.

The new model places more of the responsibility with the patient. Some will not want to take that on, and that’s OK too. Sometimes it can’t be salvaged – the personalities and goals are just too different. Patients drop doctors, and vice versa. 

Shared decision-making

The new model of doctor/patient relationships calls for shared decision-making. The doctor and patient work out the treatment plan collaboratively. This puts a greater onus on the patient, and relieves the doctor of some of his traditional responsibilities. Most doctors don’t really want to play God.

The patient must make explicit to the doctor what his priorities are. He has to think about what is really important to him, and which oncological risks and risk of adverse events from treatments he is willing to take. Are you willing to trade some quantity of life for quality of life? Are you willing to forgo ADT with radiation even though it may work better with it in the hope of diminished sexual side effects? Are you willing to try chemo earlier rather than later in disease progression to get a longer survival benefit, but knowing it may eventually fail? Do you want to put off taking ADT to have better quality of life, knowing the disease may progress unchecked? How much pain are you willing to tolerate without feeling drugged all the time? These are hard choices.

Also, let the doctor know if you are willing to enter clinical trials or be treated with an experimental protocol. Some patients want the tried-and-true, and most doctors will only offer the standard-of-care unless the patient speaks up. You have to decide for yourself if the potential benefit of an experimental protocol outweighs the risk that it might not work as well.

It helps to become as informed as you can in preparation for the meeting with your doctor. Try to meet the doctor on his own terms and with his own terms. On his own terms means that the information you accumulate is of the same quality as his information – studies published in recognized peer-reviewed publications, rather than anecdotes from a co-worker or random Internet sites. With his own terms means trying to learn the lingo as best as you can. Know the meaning of "Gleason score", "stage" and "PSA," for example. At a meeting last year, a patient asked a doctor, “For how long will I need ADT if I have radiation?” The doctor explained that it depended on his risk level, which was a reasonable answer. However, I knew what the patient really meant (I talked to him earlier), and asked “He means, for how long must he be on ADT neo-adjuvantly?” By knowing the terminology, I got the answer the patient wanted.

The doctor has responsibilities under this model too. He is responsible for administering treatments that maximize oncological control while minimizing side effects of treatment within the limits dictated by the patient. The doctor becomes the key information resource for the patient. He should provide a realistic assessment of the risks and benefits attached to each treatment option. Full disclosure of all possible side effects should be discussed and provided in writing. He must listen to the patient and acknowledge the factors that are most important to him.

Because there is so much more shared information under this new model, Patient Decision Aids (PDAs) have been developed. These are in writing or online booklets that take the patient through all the risks and benefits and ask him to make decisions about what is important. The doctor and the patient then discuss the PDA as an aid to negotiating a mutually satisfactory treatment plan. Here’s an example of a PDA on the subject of PSA screening. But a PDA is not a substitute for a face-to-face discussion. When used instead of rather than in addition to, the results can be worse than if no PDAs were used (see this link).

Managing egos

Yes, some doctors are very full of themselves, and don’t think the patient can possibly have anything useful to say. In my experience, that is a rarity. Doctors are, for the most part, exceedingly smart and intellectually curious people. To the best of their ability, they want to do what’s best for the patient. It’s all about respect. Respect his time, his experience and his knowledge, and he is likely to return the favor. If you approach him with that attitude, ego problems are likely to disappear.

Of course, it can never hurt to let him know how much you respect him. If you have something genuinely complimentary to say, verbalize it. Let him know how much you appreciate his time and effort on your behalf. If you are gracious to him, he may be more gracious to you.

I always assume he knows at least whatever information I know. He reads full text peer-reviewed journal articles, and attends conferences. However, he may have a full patient load and may not have read about some recent finding or other. (See Research data below).

Ask questions, rather than making demands. “What is your opinion about 18 months of ADT vs 3 years?” is a better approach than “I won’t take ADT for more than 18 months!”

I hate to sound sexist, but if you can, bring your wife, or a female friend or relative along (or at least take a lesson from their communication style). They have spent a lifetime dealing with the male ego, and are just better at it. Unlike men, who are often more competitive by nature, women are more naturally collaborative. That is a much more productive interaction for the doctor/patient relationship.

Research data

Sometimes you will come across a research study online that seems perfectly relevant to your case. How should you handle it with your doctor?

The way I do it is, first of all, respectfully. I start by acknowledging that he probably has seen it. My approach is collaborative, and open, rather than confrontational and closed-minded. I try to share it, preferably via email, before my visit, if one is coming up. This gives him a chance to look at it and respond to it in a more considered way. I am also careful about sources. I would never send some “miracle cure” from a random Internet site. It is always based on peer-reviewed medical evidence. I am also open to refutation: I may not have understood why that case does not apply to my case; I may not know that there are more recent findings, possibly from a higher level of evidence; or, I may have misunderstood the findings or conclusions.

During the visit

You get the most out of the doctor/patient relationship if you come to the visit prepared.

• Bring your medical records with you (e.g., PSA results over time, biopsy, prostate size, staging, pathology report, medication history). I keep all my records in a computer file for easy access and retrieval.

• Bring a written list of your questions. If you try to remember – you won’t. It’s just too stressful, and there’s too much time pressure. I like to print them out and leave space to write down the doctor’s answers.

• Take notes. It’s just too easy to miss something when you’re trying to absorb so much all at once, often with unfamiliar terminology. It’s also a good idea to record the conversation, with the doctor’s permission, and to transcribe it to a computer file later. That forces you to go over it and may help you recognize that there was something that requires clarification. However, it is tedious to listen to a long meeting, and in my experience, most patients do not review the recording. Notes are better.

• Bring someone with you. Two sets of ears are better than one, as are two sets of notes. Afterwards, stop for a coffee and de-brief. Compare your notes. Did you both hear the same thing?

• Write a summary of the meeting. I email it to myself so I have a permanent record. It’s not a bad idea to email your doctor a brief thank you note, and highlight what was discussed, agreed upon or left open, and what the next steps will be.

Communications

We all want to eliminate unnecessary visits, but keep the essential ones. You may have to visit the doctor for treatments, certain tests, to update the diagnosis, to change the treatment plan, or to discuss side effects and remedies. But it may not be necessary to have a visit just to check in, or discuss every lab test. There should be an agreed upon purpose or goal for each visit.

I think it’s usually a good idea for the doctor to call/fax an Rx for lab tests ahead of your visit with him. Your visit becomes more productive when you can sit down together to discuss the lab test results and any actions to be taken because of them.

Most communications with your doctor can probably be handled with a quick email. Most medical centers are moving towards email communications and away from phone communications. I hope that waiting for the doctor’s phone calls, and playing “phone tag” with him will soon be a relic of the past. Also, it avoids playing “telephone” with a string of intermediaries who put their own spin on the message. If you keep it brief and to the point, email messages can be a lot more efficient and effective. It also facilitates sending copies of studies you may want his comments on.

Multiple Doctors


When faced with the primary therapy decision, there may be a large number of doctors you meet with - one or two urosurgeons, an IMRT specialist, an SBRT specialist, one or two brachytherapy specialists, a specialist in proton therapy, a specialist in ablation therapy, an active surveillance specialist, as well as experts in special diagnostic tests. It is tempting to want one doctor to be a "quarterback" and some doctors advertise themselves as doing that. I recommend that you resist that urge - never give up your power, and rely only on doctors with specific expertise. There is no doctor who knows anything close to what experienced practitioners know (which will not prevent them from expressing opinions). Get your information directly from the experts, and assess it yourself. It can be a formidable task, so take your time. There is no rush - even men with high risk prostate cancer did no worse if they waited 3 months between diagnosis and treatment.

Some hospitals offer a team approach - sort of like one-stop shopping. All their best experts give you their opinions. Ideally, you would want to pick your own best doctors, but if you belong to an HMO, that may not be possible. If you have to have a team approach, it is best if you meet with each team member separately. Doctors are often reluctant to contradict or disagree with one another in the same room.

Sometimes it is time to move on from one kind of specialist to another. After radiation therapy, you may want to see a urologist or a proctologist/gastroenterologist to manage symptoms. Similarly, after prostatectomy, it can be useful to see a specialist in sexual medicine. If PSA increases steadily post-prostatectomy, patients should see a radiation oncologist. If all salvage therapies have failed, that is the time to see a medical oncologist.

Managing your records

Good recordkeeping is essential to good communications with your doctor. Communications are so much easier when you don’t have to guess what some report said, but can look at the actual report instead and agree on the facts.

Keep copies of all lab tests and reports. Computerize the results if you can for easier access and organization. If it’s too much trouble to enter lab test results on spreadsheets, at least scan them into your computer. To that end, I ask my doctor’s office to email me copies of all reports. With the new hospital and lab report email systems, it’s already online for me. I like to send myself copies anyway, in case I someday lose access to those systems.

I like to keep a log of all my doctor visits – just the date, the doctor, and some brief notes about what was discussed. It is handy for billing, as well as tracking the history of the disease.

There’s one chart that I find invaluable, and it's one that doctors love. That’s a chart of my PSA over time, on which I also note key events like biopsies and therapies. 

Assessment Questionnaires

It is equally important that the doctor evaluates and tracks the patient’s subjective symptoms in addition to his objective symptoms. Another series of records I like to keep is my qualitative assessment of my condition over time. 

A popular instrument for tracking quality of life with prostate cancer is called the Expanded Prostate Index Composite (EPIC). It’s a validated questionnaire used to obtain the patient’s subjective assessment of his quality of life based on urinary, rectal and sexual dimensions. Many doctors will ask you to fill it out before treatment begins to get a baseline measure. Then you fill it out periodically to track your progress on those dimensions. My RO uses it as a springboard for discussion at each visit. You can download a copy here and take it, score it,(scoring instructions here) and track it over time, even if your doctor doesn’t. It might lead you to want to discuss some aspect of it with him. Another version is called the UCLA Prostate Cancer Index (UCLA-PCI). Other tests sometimes used are the International Prostate Symptom Score (IPSS) that only tracks urinary symptoms. An instrument for measuring sexual function is the International Index of Erectile Function (IIEF) or the shortened version called the Sexual Health Inventory for Men (SHIM)

For cancer patients, the performance status is often tracked using the Karnofsky Performance Status Scale or the ECOG Performance Status. There is a questionnaire, often used in Europe, for tracking the patient’s quality of life with cancer called EORTC QLQ-C30

Your doctor will probably also fill out a co-morbidity evaluation. The Charleson Co-Morbidity Index or the Adult Co-Morbidity Evaluation- 27 (ACE-27).

Finding the right doctor

With most other kinds of cancers, the patient (after a diagnosis) works with an oncologist, who brings in other specialists as needed. With prostate cancer, patients always start with a urologist. That urologist may have also performed the biopsy, and he is often a urosurgeon as well. Sometimes he is a urologic oncologist. Many patients never get further than the first urologist, and that is almost always a bad idea. Patients should interview several specialists before deciding upon the one who he will share decision-making responsibility with. Depending upon the initial diagnostic information from the biopsy, PSA, DRE, and (rarely) a bone scan/CT, the patient may want to consult with a urosurgeon, at least one radiation oncologist, a medical oncologist, or sometimes, a urologist specializing in active surveillance, or a specialist in ablation therapy. If salvage treatment is needed, a radiation oncologist or specialist in ablation therapy may be needed. How does a patient find the best doctor for the job?

Available doctors/treatments – HMO vs PPO

You may be limited in the doctors and treatments accessible to you. If you have insurance with an HMO, you are limited to those doctors. Even with PPO insurance, some doctors will be out-of-network. On your current plan, you may not have affordable access to the doctor or treatment you want. If that is the case, and your variety of prostate cancer is slow growing, consider switching plans at the next open enrollment period. Insurance companies are not allowed to turn you down for pre-existing conditions.

Doctors accepting patients/ insurance/ Medicare

You won’t always be able to get the doctor you most want. Some doctors don’t take Medicare. Some don’t take any kind of insurance. Some aren’t taking any new patients. Sometimes it helps to approach a doctor with a reference from a colleague. I once got a second opinion from a famous specialist through pleading and crying -- whatever works. Have several doctors on your list as backup.

Ability to travel for treatment

There may be some very good doctors in community practice, but, according to database studies, patients generally do better with more experienced doctors, and those doctors are more likely to be found at major tertiary care centers. Some of those doctors will be out-of-state. The important considerations are whether you can afford to travel for a treatment, and whether your insurance will pay an out-of-state doctor.

Below are some typical treatment times. Can you afford to travel for them? There will also usually be an earlier trip for imaging and perhaps fiducial placement for radiation:
• PET scan (diagnostic): 2-4 hours
• Surgery: 2-10 days, depending on complications
• LDR Brachy (seeds): 1 day treatment, 1 day follow-up a month later
• HDR brachy (temporary implants): 2 days -- Sometimes a second 2-day stay a week later
• Combo IMRT with brachy boost: about 5 weeks
• SBRT – every other day for 4-5 treatments
• IMRT, proton – about 8 weeks of treatments
• Focal ablation: outpatient
• Salvage radiation after surgery: about 7 weeks of treatments
• Salvage brachy after radiation: 1 day

Finding doctors

Use your networks. I told everyone I knew that I had prostate cancer and was looking for doctors. My primary care physician knew a couple of good ones, more came from family, friends, and co-workers. Online boards are invaluable. Post with a title like “looking for an HDR brachytherapist in Kansas.” Someone may know someone who knows. 

Check rating sites like Yelp, ZocDocHealthGradesVitalsRateMDs, and UCompareHealthCare, but remember that people who bother to write typically have extraordinarily good experiences or extraordinarily bad experiences. The ordinary experiences tend to be under-represented. There are also disguised ratings from disgruntled employees, ex-spouses, friends, etc. Many hospitals and some doctors in private practice now routinely ask patients for doctor evaluations, and they are often available online. I’m particularly impressed by doctors who take the trouble to respond to negative reviews. Such sites are a good thing to check after you’ve narrowed your list down to just a few doctors.

Join a local prostate cancer support group. You will meet men with definite opinions about doctors they have used. Some organizations, like the Cancer Support Community, UsToo, and Malecare, may run groups locally. Sometimes hospitals run them. They should be easy to find with a Google search.

There are a couple of doctor finder and rating services worth looking at. The US News & World Report Doctors, which is free, is a searchable database of doctors and their profiles. CastleConnolly has a Top Doctor rating service that you can access for $2/month. They also publish Top Doctors books annually.

Specialists usually know one another. They go to conferences together, read and referee one another’s research in peer-reviewed journals. If you know a specialist that you can’t access because of insurance or distance, call his office and ask if he has a recommendation in your city.

Pubmed is a great way to find out who’s who in the specialty of interest. In the search bar, enter “prostate cancer” and “your city” (use the quotation marks) to generate names of doctors in your city. You can narrow the specialty of interest to you by using search terms like “biochemical recurrence,” “salvage brachytherapy,” “Active Surveillance,” etc. If you already have some names, it may be a good idea to check them out on Pubmed. In the search bar, enter “Doctor’s Last Name First Initial”[author] and “prostate cancer.” It will come back with a list of publications written by that doctor (make sure it's not a different doctor with the same last name), and will show you the topics that are of special interest to him. If you click on “Author Information,” it will show the hospital where he works and perhaps some contact info. Be sure to Google him as well – doctors may move to different hospitals.

Check Google Books as well. If the doctor was invited to write or edit a book that is used in medical schools to teach new doctors, chances are that he is an acknowledged expert in that field.

If there is a tertiary care center or other hospital that you have access to, they usually have websites that list their staff and their resumes. Check them out in Pubmed, CastleConnolly, and with your online network.

Experience counts. This may be especially true for surgeons and LDR brachytherapists, where the best practitioners are accomplished artists. There are several studies that have shown that surgical outcomes, both in terms of cancer control and side effects are vastly better at high volume hospitals and among the highest volume surgeons. Based on this, some have suggested that prostate surgeries should only be performed at tertiary care centers.

Go to the best that you have access to – you deserve it.

OK, so you’ve generated a list of potential doctors that you have access to. What now? Set up appointments and start interviewing them. Most will allow self-referrals, but some will only take patients referred by other doctors.

The Interview

This is like a job interview. You are assessing whether his knowledge and experience is right for you. But you are also assessing whether he is the type of person you can work with. Before deciding on whether he or she is a good fit, you have to do a frank self-assessment. 

How do you prefer to come to a decision? Ask yourself:

1. Do I want to make the key decisions myself, or
2. Do I want to relegate those decisions to the doctor, or 
3. Do I want to collaborate in shared decision making? (best idea!)

How much information do you want to deal with? Some people have the attitude “Bring it on! There’s no such thing as TMI.” Others have the attitude “He is paid to know all that.”

What are the trade-offs you are willing to make between oncological outcomes and quality of life, and will the doctor be willing to accept your decisions about this?

For suggested questions to ask on interviews, see the following links:
Questions to ask (and not ask) on a first urologist visit after a biopsy
Questions to ask on a first visit for primary radiation therapy (IGRT/IMRT)
Questions to ask an SBRT specialist
Questions to ask a low dose rate (seeds) brachytherapist
Questions to ask a high dose rate (temporary implant) brachytherapist
Questions for a focal ablation therapist
Questions for an adjuvant or salvage radiation doctor

Questions to ask yourself


Personalities

Doctors are people too. They have the same diversity of personality characteristics that everyone else does. Some of us will not want our choice of doctor to be at all influenced by personality. Others cannot imagine working with a doctor they don’t respond to personally. 

Here are a couple of comments from patients in my support group:

“I know he is the top surgeon in the area, but he was arrogant. He didn’t listen to anything I had to say and swept aside my concerns as if they were unimportant. He didn’t seem to think there was any risk, as long as I went with him, and oh, by the way, he has an opening next week on a DaVinci that he can squeeze me into. He has a huge ego and wants to play God. I never went back.”

“He has done more robotic surgeries than anyone. He assures me that the operation will be a complete success and that very few of his patients suffer lasting incontinence or lasting ED. His self-assurance makes me feel comfortable turning myself over to his capable hands.”

Here are another two comments:

“He didn’t look me in the eyes once during our meeting. He recited a long list of possible side effects and quoted probabilities from a variety of research studies. He refused to give me a firm recommendation, and told me it depends on what I want. He is a complete nerd who should be calculating statistics rather than dealing with patients.”

“He had all this amazing data at his fingertips. He gave an honest appraisal of all the risks and the benefits associated with each treatment. He gave me everything I needed to make my decision. It was exactly what I needed.”

Each pair of comments described the same doctor. Within each pair, the personality of the doctor was the same, but the personality of the patient was very different. You have to start with a frank self-assessment before you decide what personality characteristics are important to you in choosing a doctor.

Here are some questions to keep in mind as you conduct your first interview with a potential doctor:
• Does he listen?
• Does he adequately address my concerns?
• Do we speak the same language? Do we communicate?
• Does he provide full disclosure?
• Does he make me feel like a human being, or an object?
• Is he rushing me into a decision?
• Is he telling me what I need to know to make an informed decision?

Remember that a good “bedside manner” does not necessarily translate into a competent doctor, as comforting as his presence may be.

Ongoing communications

It’s a good idea to establish how future communications will occur. I prefer to choose doctors who are willing to establish direct lines of communication with patients. 

I find phone calling to be a frustrating way of communicating. Because of HIPAA rules, he probably can’t leave a full message. He will seldom be available to speak to you when you call. Often there are gatekeepers you have to get through when you call. Assistants and nurses, though well meaning, may not always get the message exactly right. Avoid asking them questions that only your doctor ought to answer. It puts them in an awkward position, and may lead to errors.

During my first interview, I ask if the doctor is willing to communicate via email. My favorite doctor replies promptly to my questions, typically within minutes. I respect his time by keeping my questions brief so that I don’t abuse the privilege. In this way, we avoid playing phone tag.