Advances in Radiation Oncology for the Treatment of Prostate Cancer
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| Brent S. Rose, MD, Radiation Oncology, UC San Diego |
1. Focal Radiotherapy Boost of Dominant Intraprostatic Nodule
Prostate cancer is usually multifocal, with a dominant nodule (tumor), and one or more other smaller tumors. So “whole-gland” radiotherapy has been necessary up to now to treat all of the cancer. Often after radiation, the cancer comes back in the dominant nodule area, so it is hypothesized that that nodule reflects the most aggressive part of the tumor. A new goal is to increase the dose to that highest risk area, without significantly increasing the dose to surrounding tissue. Some details, such as how much boost to give, are still being worked out on a case by case basis. But use of this approach is expected to increase.
2. Treatment Response Assessment with MRI
When a patient is being treated for prostate cancer, it is important to learn quickly whether the treatment is working. This could allow for dose escalation (or even de-escalation), based on whether the response of the tumor(s) to the treatment is favorable or not.
Multiparametric MRI is the best way of imaging localized prostate cancer. The key parameters are T2 (for anatomic detail), Dynamic Contrast Enhancement (showing tumors because of their greater blood supply resulting in fast uptake of the contrast agent), and Diffusion Weighted Imaging (showing areas of dense tissue, which signifies a tumor – and the density correlates with Gleason scores!). At UCSD, an advanced diffusion weighted imaging technique called Restriction Spectrum Imaging has been developed. The anatomic detail of the T2 parameter is overlaid on the DWI result, and this gives a precise understanding of where the tumor is, and is very helpful in planning for focal radiation treatment.
3. Sexual Potency-Preserving Radiotherapy
Erectile dysfunction is one of the most significant complications of prostate cancer treatment. One of the common pathways for escape of the cancer from the prostate is along the nerves of the “neurovascular bundle.” So surgery often involves cutting these nerves to get out all the cancer. That negatively affects sexual potency. The (typically smaller) impact of radiation on erectile function is likely due instead to irradiation of the vasculature (blood vessels) of the penis, resulting in decreased blood flow. It’s as though the radiation causes accelerated aging, leading to buildup of plaque and less blood flow to create erections.
By directing the radiotherapy appropriately, with the aid of an MRI scan, the blood vessels can be spared much more precisely than in the past when only CT scans (which don’t show prostate anatomy well) were used for planning. With this precise targeting, critical normal structures can be avoided, and the need for ADT (hormone therapy) may be avoided or reduced. Although the radiation field typically includes the neurovascular bundle, the nerves are relatively resistant to radiation, so are not adversely affected very much. Sexual potency is more often preserved compared to results after surgery. See European Urology, 72 (2017) 617-624.
4. Treatment of Oligometastatic Disease:
This is prostate cancer with 1-4 metastases, typically in the lymph nodes or bones. Preliminary literature reports suggest that aggressive treatment may improve survival. In a case example given, a bone scan gave (as always) poor sensitivity and specificity, but an F18-Fluciclovine (“Axumin,” radiolabeled amino acid) PET scan showed a distinct area that could be treated with radiation. Other agents can also be used in PET imaging, including C-11 and PSMA tracers, but they are not FDA approved, so insurance won’t pay for them [but see last month’s Q&A for PSMA at UCSF paid for by Medicare]. In the case shown, MRI gave very distinct identification of the metastatic lesion, near the prostate, and the patient was treated with stereotactic radiation therapy (a short course of high-dose radiation). In some cases, prostatectomy may be done in addition. ADT may follow for a time, possibly including abiraterone (Zytiga).
UCSD has opened a study for cancer patients with high-risk or known metastatic disease, with a goal to test the accuracy of whole-body MRI to identify sites of metastatic disease.
Questions:
If on Lupron, can one use the advanced diagnostic tests (PET with tracer)? Yes, but … Lupron tends to put the cancer to sleep, so it’s harder to see the lesions. It’s still possible to find them if looking carefully.
When should one use proton therapy instead of IMRT? Studies are underway, but in general results are very similar. Side effects are about the same. Protons don’t pass all the way through the body, so that’s an advantage for some cancers, like brain cancer or the spine (but not demonstrably so yet for prostate cancer). It takes a very powerful (large!) machine to accelerate the protons, and this physically interferes with following the therapy by daily imaging. However, improvements are being made.
PIRADS scores vs. Gleason Scores? Not equivalent, but they tend to track together.
MRI after surgery – does it correlate with PSA level? Usually MRI after surgery is not very helpful, because any remaining tumor is likely very small and hard to see, especially in and around scar tissue. Axumin or C-11 scan is likely to be more sensitive in that case.
SpaceOAR (gel injected between prostate and rectum before irradiation) pros and cons? Great in theory, but how much it really matters, and what the side effects are, are still not fully determined. A very slight benefit has been shown in published studies. But, a few patients got fistulas. That’s serious, though rare, and not proven if caused by the injection rather than something else. At UCSD, they find the gel is not necessary because the rectum is not significantly damaged even when the gel is not used. Note: It’s not covered by some insurance, and costs up to $5,000.
Qualifications for the whole-body MRI research study? They are very broad: having high risk for metastatic disease (newly diagnosed) or known metastatic disease are the only requirements. Also, patients with recurrence (elevated PSA) after surgery are eligible.
What to do if one has Gleason 6 and PSA = 5 with two cores positive? You would be unlikely to find anything with MRI, but could get the scan to be sure that a more aggressive tumor wasn’t missed. Dr. Rose said this member is a candidate for active surveillance ... and continuing to attend IPCSG meetings! But he should also consider talking to a radiologist and to a surgeon. If more cores were positive, then the advisability of an MRI would rise.
MRI after surgery and radiation? Not likely to find anything if the PSA is, say, 0.2, but you may see something if it is 2 or more. A whole-body MRI might be helpful, to look for metastases.
With a rising PSA after external radiation, with Gleason 7, and apparent local recurrence in the prostate, when should one “pull the trigger?” Surgery is likely to cause incontinence. Brachytherapy (radioactive seeds) or cryotherapy may be appropriate. Whole body imaging may be useful to look for metastases. Decisions depend on the details of the case. Not a clear-cut path forward that would fit all such cases.
Having recurrence after surgery, in the seminal vesicles, with radiation planned for the new tumor – should Lupron be used before radiation, to shrink the tumor? It is likely to shrink the tumor, but it’s not known if and how much help that would be, for avoiding irradiation of the bladder.
How relevant is the patient’s age – from a member who is 87? His PSA is 0.3, and his doctor recommends discontinuing Lupron. Dr. Rose advised him to make his own decision, considering quality of life and length of life.
Testosterone supplementation? Recent consensus is that if the PCa stays low after initial treatment (such as surgery and/or radiation), that supplementation to a normal testosterone level to improve quality of life, may be acceptable (and not fuel the cancer too much). This recovery of the testosterone level occurs naturally in younger men, so supplementation doesn’t seem too dangerous in older men. If the cancer is coming back, the testosterone supplementation probably will “fuel the fire” a little bit. That is likely to make the PSA rise faster, and result in going back on Lupron faster. It’s a personal choice.
If you have external beam (e.g., IMRT) radiation, and the cancer comes back, can you get radiation again? Yes, but the side effects are high if more IMRT is given. Proton therapy would likewise not be advised. Your body “remembers” that you had radiation. The first dose is usually as high a dose as the body is likely to tolerate. But cryotherapy, brachytherapy (seed implants) or SBRT (very focused radiation) are possibilities that may limit the side effects.
Tumor recurrence in the same spot five years after IMRT and ADT – what to do? The member had heard there is a two-part radiation treatment. Dr. Rose surmised that this was a reference to a brachytherapy boost, where seeds are implanted in the prostate to allow a much higher dose to the tumor than can be given by external radiation (see also the next question response below). Other options are cryotherapy, SBRT (but rare in this type of case), and nanoknife (Note: a talk on Nanoknife, also called IRE – Irreversible Electroporesis – was given at the IPCSG last September. The video is available through the group website, and a summary of the talk is available by contacting this author at lewis.bill@gmail.com)
More info on brachytherapy? Often used at UCSD. One situation is for first treatment after active surveillance suggests some treatment is advisable. It is a one-day procedure with good efficacy, and has low side effects. Affects the urinary tract somewhat, but spares the erectile function. The second situation is use in combination with external radiation and hormone therapy, with published results showing good control of cancer within the prostate. The combination gives a high dose in the observed tumor, plus a surrounding margin of radiation to eliminate other small tumors.
Usefulness of MRI-guided biopsy – required before brachytherapy? Not “required” for it or other therapies, and thus may not be paid for by insurance, but he would choose it if newly diagnosed, to gain the best understanding of the disease status.
Is RSI-MRI better than mpMRI? Dr. Rose thinks so. It gives better identification of high-grade tumors, and helps avoid being fooled by things that are not tumors. Not 100% better; more like 20% better.
Differences between locally available proton therapy, and that at Loma Linda? Here, we have IMPT (Intensity Modulated Proton Therapy), which is more sophisticated than Loma Linda center’s proton therapy.
