In interviews I did for the Prostate Cancer Foundation’s website, Weill Cornell Medicine urologist Jim C. Hu, M.D., M.P.H. (whose expert opinion also was featured in our book), breaks down what rising or persistent PSA means after treatment for localized prostate cancer, and what you should do next.  Remember the first lesson from Part 1:  Don’t panic!

             How do you know if localized prostate cancer is cured?  That answer to that question is straightforward for men who undergo radical prostatectomy:  in the weeks after surgery, the PSA should become undetectable, falling to less than 0.1.

But for men who undergo radiation therapy, it’s more complicated: there is no definitive PSA cutoff point that signals success or failure of treatment.  That’s because radiation therapy – external-beam or radiation seeds (brachytherapy) – is designed to kill prostate cancer, not normal prostate tissue.  It doesn’t kill the entire prostate – and thus, PSA does not go away completely.

Instead, PSA drops, eventually reaching a rock-bottom level called the PSA nadir.  Note:  there may be a little bump along the way, called the PSA “bounce.”  This doesn’t happen to everyone; it’s more common in younger men.  The PSA bounce does not mean that you are not headed for a low, stable PSA.  It’s just a weird thing that may be related to inflammation of the prostate; it’s temporary and usually happens within the first two years after treatment. Then PSA usually settles down, remaining at a very low level.

It can take anywhere from two to five years after radiation for PSA to bottom out.  If it starts to climb back up, further tests are not indicated until the PSA reaches the nadir value + 2 ng/ml.  “The very term, ‘nadir +2,’ tells you that whole-gland radiation is not expected to kill all the cells within the prostate,” says Jim Hu.  “There are some benign cells left behind that can still make PSA.  But if there are also some remaining cancer cells, those cells will grow over time, and finally produce enough PSA to exceed that nadir + 2 cutoff.”  Thus, if cancer is still present after radiation therapy, it may take months or even years to find out about it.

If Some Cancer is Still There, Where is it?

There are several possibilities as to where the cancer might be lurking, says Hu.  “The cancer could be just within the prostate.  It could be within and outside the prostate, but still in the nearby area.”  Or, it might be further afield – in a lymph node, perhaps.  “It may be that the radiation killed the cancer within the prostate, but there were some microscopic metastases outside the prostate that were not touched by the radiation.”

The first place to look for recurrent cancer after radiation therapy is within the prostate – with an MRI and a biopsy.  What happens next?  Let’s say the cancer is still in the prostate.  “Typically, you can’t do more radiation to the prostate because that part of the body has already tolerated the maximal dosage of radiation,” says Hu.  “But at some centers, they will put some radioactive seeds (this is called brachytherapy) in the area where the cancer is, or within the prostate.”

What about surgery?  Many centers do not offer “salvage” prostatectomy, “because the delay in diagnosing the recurrence means the cancer might have spread.  Some salvage radical prostatectomy series [studies] showed that the likelihood of cure (with surgery after the radiation) was only 20 to 30 percent.”  Hu has performed 20 salvage robotic prostatectomies, but he makes sure his patients know that complications are much more likely when surgery is performed on an area that has undergone radiation therapy.  That’s because the tissue is already damage to start with.  “The incontinence risk, instead of being 1 to 2 percent, is now 50 to 80 percent for stress urinary incontinence (when urine leaks during certain activities, such as exercise), and there is a higher risk of the rectal tissue – which becomes fragile after being irradiated – developing a hole or tear (called a fistula).

Other options:  High-intensity focused ultrasound (HIFU) of the entire prostate is another option, and so is cryotherapy (freezing the tissue inside the prostate).  Both of these options, currently being offered at some centers as focal therapy, have a lower risk of incontinence and ED than salvage prostatectomy, Hu explains – but notes that here again, PSA will most likely not become undetectable after treatment.  Instead, it’s back to waiting for the PSA to reach its nadir.  And if you have a PSMA PET scan or other imaging showing that cancer has spread outside the prostate area, such as to bones, you and your doctor will need to discuss starting ADT, by itself or along with an androgen receptor-targeting drug such as enzalutamide or abiraterone plus prednisone for a combined punch.  These medicines lower testosterone, cutting off the cancer’s “fuel supply,” and can be effective for many years.

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

© Janet Farrar Worthington

 

In interviews I did for the Prostate Cancer Foundation’s website, Weill Cornell Medicine urologist Jim C. Hu, M.D., M.P.H. (whose expert opinion also was featured in our book), breaks down what rising or persistent PSA means after treatment for localized prostate cancer, and what you should do next.  Remember the first lesson from Part 1:  Don’t panic!  

            Let’s say a prostatectomy patient’s first PSA after surgery was less than 0.02 at three months, but at one year is 0.1.  “If that patient is high-risk (see below) to begin with, that’s a pretty clear signal that this particular patient is probably going to have a recurrence,” says Jim Hu.  “On the other hand, if that patient were Grade Group 2 (Gleason 3+4=7), had negative margins, had low-volume disease confined to the prostate, and then had a 0.1 PSA, there’s more of a comfort level in having a higher threshold, in waiting to let it declare itself further.”  The advice here would be to wait another three or six months, and check it again.  “You want to give it long enough to see if anything has changed.”

—

Do You Have High-Risk Cancer?

Features that indicate aggressive cancer and higher risk of recurrence:

*Positive surgical margins

OR

*Seminal vesicle invasion

OR

*N1 lymph node involvement

OR

*High-grade (Grade Group 4 or 5; Gleason 8, 9, or 10) cancer

OR

*Pathologic stage of T3b

—

            Is there a magic number that signals further action is needed?  The American Urological Association and the Society of Urologic Oncology recommend a cutoff of 0.2.  “Some literature and research have suggested you could even hold off until 0.4,” notes Hu.  “The new guidelines say that for detectable PSA after radical prostatectomy, when radiation therapy is considered, clinicians should provide salvage radiation when PSA is less than or equal to 0.5.  At 0.4, there is still debate among radical prostatectomy surgeons that you could wait longer to let the cancer declare itself.”  (A genomic test may help; see below.)

Here’s a big question:  is it actual prostate cancer causing the rise in PSA, or just some leftover prostate cells?  “Everyone does this surgery a little differently,” says Hu.  “It could be that a little bit of benign prostate tissue was left behind, especially if the surgeon did aggressive nerve sparing.”  The nerves responsible for erection sit in two neurovascular bundles outside the prostate, and are left intact in the “nerve-sparing” prostatectomy – if there is no cancer nearby.  (If cancer is too close, one or both neurovascular bundles may be removed.)  But it is possible, if a surgeon is really trying to stay away from those nerves, that some prostate cancer cells may be missed.

Thus, this prostate tissue could very well be benign – but because these are prostate cells, and prostate cells make PSA, that PSA could become detectable over time.  Or, there could be cancer in this prostate tissue.  “This comes back to the risk,” says Hu, “and there needs to be shared decision-making, or patient involvement, in the decision of what to do next.”

Can PSMA-PET imaging help?  Yes, but not when the PSA is very low.  “PSMA-PET is unlikely to show anything until the PSA gets to 0.4 or higher,” Hu explains.  “Many patients get a PSMA-PET scan before surgery if they have high-risk disease, but we often do a repeat PSMA-PET if their insurance allows it,” because their next step is salvage radiation.  “The radiation oncologist may want that imaging study, as well, to determine whether to extend the radiation field.  But at PSA below 0.4, it’s unlikely that anything is going to light up” to show whether there is residual cancer, and where it is.

What Happens Next?

Let’s say a man has a prostatectomy and one of his PSA follow-up tests shows the PSA has gone from being undetectable to being 0.1 ng/ml.  What should he do?  Wait until the next test, and see what happens.  “To be concordant with guidelines, you wait until the PSA reaches 0.2 before you see a radiation oncologist.”

Could a genomic test provide helpful information here?  Decipher and other genomic tests examine prostate tissue (either from a biopsy or from the prostate specimen after prostatectomy), looking look for genes that are known to be involved in aggressive prostate cancer.  If you did not get a genomic test at diagnosis, getting one now may help determine your next steps.  For example, using the Decipher score, cancer that is less aggressive shows up as less than 0.45; intermediate risk cancer is less than 0.6, and high-risk cancer is from 0.6 to 1.0.

            How might this help you and your doctor decide what to do next?  Do you need “salvage” radiation (radiation given after prostatectomy)?  And do you need a temporary course of ADT, as well?  Hu gives an example:  “’The PSA is 0.2 or higher.  Let’s send off the Decipher, see if it is favorable, and then we can just do the radiation without androgen deprivation therapy (ADT).’  That’s where shared decision-making comes into play, because of the undesirable side effects of ADT.   There are many reasons, ranging from masculinity concerns to worries about bone fracture, why the individual may want to avoid ADT – and a low or intermediate Decipher score may reinforce their desire to avoid it.”  But the stakes are higher this time, he cautions.  “If it were me, I would take the short course, four to six months of ADT, along with the radiation to make sure that we get the cancer.   We’ve already missed one chance to get a cure.”

Treatment Options

The standard of care treatment for a rising PSA after prostatectomy is salvage radiation therapy to the prostate bed(where the prostate was) and potentially to the entire pelvis.   The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines recommend that if a patient has high-risk features (see above) after prostatectomy, and if there is a short PSA doubling time (if it doubles in less than 6 months), he should also get four to six months of ADT in addition to salvage radiation therapy.  “This maximizes your chance at a cure,” says Hu.

Note:  If salvage radiation therapy is the next step for you, sooner is better than later, and this is why early PSA monitoring is so important.  “There is strong evidence that for a detectable PSA after radical prostatectomy, salvage radiation is more effective when the PSA is at 0.5 or lower,” says Hu.  However, if you are at high risk for clinical progression, and you have a detectable PSA, your doctor may recommend starting salvage radiation when the PSA is at 0.2.  “Here again, shared decision-making is really important,” because salvage radiation is going to an area that has already gone through the upheaval of surgery.  This means that the risk of side effects, including problems with urinary control, ED, and bowel function, is inherently higher.

To Recap:  

If this feels confusing….that’s understandable.  These decisions are complex, and because each patient’s situation is unique, there’s no one-size-fits-all answer.  In general, consider the following thresholds, and consult your doctor:

• Do not skip your PSA monitoring appointments.
• PSA rises to 0.1: Recheck in 3 months. Patients who had high-risk disease features at surgery may need to act sooner
• PSA rises to 0.2: See a radiation oncologist and consider a genomic test of prostate tissue to better understand your risk of aggressive, recurrent prostate cancer
• PSA rises to 0.4: Consider a PSMA PET scan to look for small amounts of cancer in the pelvic region or elsewhere in the body.  Consider starting salvage radiation therapy with or without ADT

Next: Part 3:  What if PSA never becomes undetectable after prostatectomy?

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

© Janet Farrar Worthington

 

Meet Jeff Finerman, prostate cancer survivor and exceptional responder.  

            A couple months ago, I got one of the best emails ever.  It came from Jeff Finerman, a man I had interviewed in 2017 for the Prostate Cancer Foundation (PCF)’s website.  When I wrote that story, I began with these very true words: “Metastatic prostate cancer can turn on a dime.  For too long, a sudden shift in the disease has meant bad news.  But now, more men are seeing a sudden turn in the right direction.  Jeff Finerman is one of them.”

Jeff had experienced an excellent response to Zytiga (abiraterone plus prednisone, an androgen receptor-blocking combination), along with Lupron, a form of androgen deprivation therapy (ADT), and Xgeva, a drug that specifically targets and strengthens cancer-riddled areas in the bone.

No one had any idea just how good his response would be.  In his email, Jeff said: “Last week, my oncology team of many years declared my cancer in full remission. I am the first person with stage 4 metastatic prostate cancer with numerous tumors on my bones that’s ever gone into full remission to their knowledge.  When you research my severity of cancer, the typical life expectancy once metastasized to the bones is in the neighborhood of two years, I just completed my 10th year. They’ve stopped 100% all injections and all medication related to my advanced prostate cancer. What a way to start the new year!”

I had to read that last sentence again.  Wow!!  I asked if I could do another interview, and he agreed.

What Makes Your Particular Cancer “Tick?”

Before we continue Jeff’s remarkable story, there are some important points we need to consider:

Every man’s prostate cancer is different.  Let’s say several men, sitting in a doctor’s waiting room, happen to be diagnosed with the identical stage and grade of cancer.  Although it might seem that they should all respond the exact same way to treatment, this hardly ever happens – because, like snowflake crystals, each man’s particular prostate cancer has its own unique genetic and molecular makeup.

When it comes to treating advanced prostate cancer, the mechanisms and pathways that make your cancer “tick” may be completely different from those of the next guy in the waiting room.  One size does not fit all.  For example: one man in our waiting room might have an altered gene, such as BRCA1 or BRCA2, which can make the cancer more responsive to medicines called PARP inhibitors.  The man in the next chair might have a less common form of prostate cancer, with a faulty DNA mismatch-repair gene and high “microsatellite instability” – cancer that is more responsive to an immunotherapy drug such as pembrolizumab (see the story linked below).  Another man, like Jeff, might have a very high percentage of cancer cells that are sensitive to hormones, and his cancer might respond mightily to androgen deprivation therapy (ADT) and an androgen receptor pathway-inhibiting drug, such as enzalutamide or abiraterone.

More new drugs are being developed all the time.  Not just new variations of drugs that do the same basic thing, but entirely new ways to treat cancer, like PSMA-targeted radionuclide therapy.  These new drugs are being tested in clinical trials.  Thus:

The playbook on treating advanced prostate cancer is always evolving.  Good oncologists are keeping up with the new treatments entering trials and the new standards of care.

Other parts of the cancer-fighting equation are very important, as well.  Jeff has two essential factors that have helped him manage his cancer:  a positive attitude, and strong family support.

   So, keep all of these things in mind as you read about Jeff.  He wants to share his story to encourage other men fighting prostate cancer, and on one key point he, his doctors, and PCF agree:  there is more cause for hope every day, and the right treatment can cause the disease to change course very quickly.

 Now, here’s his story.

Lows and Highs

Jeff Finerman had a good and pretty ordinary life until 2013, when he was diagnosed with metastatic prostate cancer at age 62.  For the next eight years or so, his life was more like a roller coaster ride, with serious lows and amazing highs.

Now, 11 years after that diagnosis, Jeff has a good and extraordinary life.  His cancer is in remission, and he has been taken off of all of the cancer-fighting agents he was taking – including hormone therapy!   He is one of a small but growing new group of prostate cancer survivors:  the exceptional responder.

Jeff’s prostate cancer journey has been characterized by many sudden shifts.  Back in 2013, his urologist was watching his PSA level closely, because it had risen to 4.  Within three months, it shot up to 23.  A biopsy found cancer in 12 out of 12 samples – aggressive cancer, with Gleason 4 + 5 disease on both sides of the prostate.  Bone scans and CT imaging showed tumors on the L4 vertebra in his lower spine.

            Jeff and his wife, Karen, were determined to fight this cancer hard.  They have faced it as a team along with their twin daughters, who were teenagers when cancer was first diagnosed.   In 2013, they did their own research and found oncologist Charles Ryan, M.D., then at UCSF (now at the University of Minnesota).  Ryan – who is also the father of twin girls – made time to see Jeff on his lunch hour.  “He gave us so much hope,” says Jeff.  “He said, ‘You’re young. We’re going to be aggressive.  We’re going to knock this.’  We owe it all to Dr. Ryan.”

            Ryan started Jeff on ADT, with leuprolide (Lupron) injections and bicalutamide (Casodex).  Jeff also received 45 treatments of external-beam radiation therapy to his prostate, pelvic area, lymph nodes, and lower spine.  He had an excellent response: the cancer shrank, and his PSA dropped to nearly undetectable levels.  In October 2014 his oncologist (Ryan’s colleague at UCSF) gave him a respite from hormonal therapy, and then restarted both drugs in July 2016, when Jeff’s PSA began to rise again.  Cancer came back in his right hip; Jeff underwent more radiation to treat it.  His PSA continued to rise, and the oncologist took him off bicalutamide.

            In 2017, a PSMA-PET scan showed only the spot of cancer in his hip – but a few weeks later, Jeff developed bone pain in multiple places.  A bone scan showed “at least a dozen tumors” – the one in his hip, now doubled in size; cancer in his right femur, left knee, several vertebrae, ribs, and clavicle.   “Every two weeks, my PSA was going up,” he recalls.  It reached 12.4, and his pain was terrible.  Jeff, who had been leading an active life, went from walking three or four miles a day plus lifting weights to lying for hours in the bathtub to ease the pain in his bones.

Jeff switched his care to UCLA, much closer to home than UCSF.  He started taking abiraterone (Zytiga^®) and prednisone, and the results were dramatic:  “Within two weeks of starting abiraterone, 100 percent of the pain was gone,” says Jeff.  “The rest is basically history.”

Jeff turned out to be a “super responder” to abiraterone and prednisone, says medical oncologist Sandy Liu, M.D., formerly at UCLA and now on the faculty at City of Hope in Irvine.  In 2018, she also started Jeff on denosumab (Xgeva^®), a bone-targeting drug that helps prevent fractures.  It was supposed to be for 11 months, “to try to strengthen the bones where I had the metastases,” says Jeff.  “I was on it for five years!  It worked so well, she just kept me on it!”

About four years ago, Jeff’s PSA became undetectable.  And about two years ago, Liu decided to do something she had never done before:  “She said, ‘We’re going to start phasing you off of everything.” 

Why do this – what happened to “if it ain’t broke, don’t fix it?”  Because hormonal therapy has significant long-term side effects, and Liu felt that Jeff, whose disease seems to have stopped in its tracks, no longer needed it.

“We will never call Jeff cured,” says Liu, “but he is in long-term remission.  He has an undetectable PSA and no evidence on PSMA-PET or other scans of active metastatic disease.”

Very slowly and very cautiously, over a two-year period, Liu tapered Jeff’s medicine, starting with the abiraterone and prednisone.  And then the leuprolide.  “It’s been over a year since I’ve had a Lupron injection,” says Jeff.  Then she stopped the denosumab.  “She said, ‘Your bone scan was so good, you don’t need it anymore.’”  Says Liu:  “His bone density scans, CT scans, and PSMA PET scans all showed nothing:  no new lesions.  Nothing has progressed since 2018.”  And of course, he will be closely followed with PSA screening and imaging for the rest of his life.

Jeff’s only medicine now is for his heart, after valve repair surgery.  “I had a couple of bad valves in 2013 when I was diagnosed with metastatic prostate cancer,” says Jeff.  “The conclusion was that the cancer’s probably going to kill me, so we’re not going to worry about the heart.  My life expectancy at that point was not very positive.”  Also, the surgeons and Liu had worried that the surgery would somehow disrupt or activate Jeff’s metastases in the ribs and other areas.  “Finally, in 2022, Dr. Liu went ahead and authorized what the cardiac surgeon needed to do.”

For the last two years, Jeff and Karen have been feeling “so miraculous,” says Jeff.  “Dr. Liu felt the same way.  Every time I’d walk into her office, she’d give me a big hug, and say, ‘You’re my golden boy!’  I’m doing great!  In fact, better than great!”  He does have some joint pain, which he attributes to stopping the prednisone.  He has seen a rheumatologist and undergone numerous x-rays, and “other than normal wear and tear on my joints, it all looks good.  Nobody really knows why I have that joint pain.”  It could also be related to stopping the denosumab after being on it for five years.

“Not only did I see my girls graduate high school, but they both graduated college, one with a master’s degree, and one of my daughters just got married!  When they were in high school, we didn’t even know if I would make it to their graduation.  I’m so fortunate!”

Attitude and Support

            “Jeff has the most positive attitude,” says Liu.  “He is always so upbeat.  I am convinced that this does make a difference,” in survival and in handling the curveballs of cancer – particularly, pain – and the side effects of treatment.

            He also has a dedicated care partner:  Karen.  “I go to almost all the appointments,” says Karen.  “Sometimes when you’re a patient, you might hear the words, but you’re not hearing the real words because it gets scary and it gets complicated.  I help translate that, and advocate and make sure everything’s going the way it’s supposed to go.”  He also credits his family with helping him remain upbeat.  “Nobody in my family would let me get down.”

            Jeff encourages cancer patients to bring a family member or friend to medical appointments, if they can.  For patients who don’t have that immediate support, Liu suggests taking part in an online or in-person prostate cancer support group.  “Talking about your treatment and what you’re going through with others who have faced it, too, can be very beneficial.”

            These days, says Jeff, “I wake up every morning with a smile on my face.”   What if the cancer comes back?  “Dr. Liu told me, ‘There are quite a few new meds that have come on the market since we started you on Zytiga and prednisone five years ago.  There’s been a lot of progress over the years.”   The message:  “Don’t give up!  There’s hope, and enough research being done that there are always more things on the horizon.”

            One last note:  Jeff is a U.S. Veteran, who served in the Army/National Guard during the Vietnam era, from 1969 to 1975.  PCF has established Prostate Cancer Precision Medicine centers at more than a dozen VA hospitals throughout the country, where Veterans can get precision diagnosis.  I will be posting about this soon.

In addition to the book, I have written about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org.  The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  I firmly believe that knowledge is power.  Saving your life may start with you going to the doctor and knowing the right questions to ask.  I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease.  Many doctors don’t do this, so it’s up to you to ask for it.

©Janet Farrar Worthington