Low Dose Rate (LDR) brachytherapy is a common treatment that uses radioactive isotopes to treat prostate cancer. Many patients with earlier stage prostate cancer (such as favorable intermediate risk prostate cancer) can be treated with LDR brachytherapy alone with very high long term cure rates. Multiple large retrospective studies have shown high cure rates, with 10-year progression-free-survival rates ranging from 85-95%. In addition, a large multi-institutional randomized trial showed that for many patients with intermediate risk prostate cancer specifically, the use of brachytherapy alone leads to just as good cancer control outcomes, with far fewer long term side effects, than the combination of external beam radiation therapy and brachytherapy. More can be found about the intricacies of when to and when to not include external beam radiation therapy as part of the treatment paradigm here.
Common Isotopes used in Prostate Brachytherapy
There are three radioisotopes which are commonly used for prostate brachytherapy:
- Iodine-125: This is the most commonly used radioisotope worldwide. It has a half-life of 60 days and has an average energy of 29 keV (kiloeelectron volts)
- Palladium-103: Pd-103 has a half-life of 17 days and an average energy of 21 keV
- Cesium-131: Cs-131 has a half-life of 10 days and an average energy of 29 keV
The Meaning and Impact of the Half-Life and Average Energy on Treatment Choice
The half-life of an isotope used in brachytherapy denotes the amount of time it takes for the radiation seeds to emit half of their radioactivity. For iodine, this means that half of the radiation is gone in 2 months, 75% is gone in 4 months, 87.5% of the radiation is gone in 6 months, 93.75% is gone in 8 months, etc. The half-life durations for Palladium and Cesium are much shorter.
There is one definite advantage to a shorter half-life and two theoretical advantages to a shorter half-life.
- Shorter Duration of Radiation Precautions: Patients who receive brachytherapy are given several radiation safety precautions. Specifically, I caution my patients to not have small children on their lap or spend too much time adjacent to pregnant women for at least several weeks. In addition, patients should refrain from anal receptive sex due to concerns of radiation dose to the penis of their partners. Due to the short half-life of Palladium and Cesium, these precautions can be removed earlier than if a patient gets an Iodine implant.
- Shorter Duration of Acute Short-Term Symptoms: The acute short-term symptoms of brachytherapy are due to a variety of factors including the physical trauma of the catheters/needles being put into the prostate, the subsequent swelling of the prostate tissue, and the radiation effect on the normal tissues (urethra, bladder, rectum, etc). Typically, the most common symptoms are acute irritative symptoms, such as increased urination at night (nocturia) and the sensation of incomplete urine emptying during the day. In my experience, these symptoms peak between 2-4 weeks after brachytherapy and then gradually improve between 4-12 weeks after brachytherapy with a palladium or cesium implant. These symptoms can last longer, in my experience, with an iodine implant. While there is not much clinical data evaluating the toxicity difference between the different isotope choices, one study that compared palladium vs. iodine implants did indeed find that patients who received the palladium implants had a shorter duration of urinary symptoms. The study can be found here.
- Higher-Cure Rate: This is the most controversial of the claims for using an isotope with a shorter half-life, but there are increasing data to suggest that Palladium in particular could yield higher cure rates than Iodine. A recent multi-institutional study which included over 9,000 patients treated with brachytherapy total, showed that the 7-year freedom from biochemical failure rate was 96.2% for Pd-103 vs. 87.6% for I-125. This is dramatic difference. The study can be found here. The authors of the study suggest two potential mechanisms and I have another personal theory:
- Radiobiology: Prostate cancer is believed to have a low α/β ratio. This is a radiobiology concept which suggests that a higher dose rate/hour may be more effective than using a lower date rate/hour for cancer control. Because palladium has a substantially higher dose rate than iodine (21 cGy/hour vs. 7 cGy per hour), palladium may be more effective at killing prostate cancer cells.
- Physical Placement of Seeds: Because palladium has a lower average energy than both Cesium and Iodine, more radiation seeds are typically required to adequately treat the prostate. Partially as a result of this, a higher proportion of the prostate gland receives a dose in excess of the typically prescribed dose. In my own implants, especially in patients who have a rectal spacer such as SpaceOAR placed, I often achieve a high percent of V150 (percent of the prostate gland receiving 150% of the prescribed dose) in the posterior part of the prostate. This higher dose could theoretically kill more prostate cancer cells than would have otherwise died with a lower dose of radiation.
- Physician Experience/Skill with Brachytherapy: I have another theory which the authors do not mention. Users of palladium are likely, on average, better brachytherapists, than users of iodine. Because of the lower average energy of palladium, it is more technically difficult to perform an adequate palladium implant. However, for the aforementioned reasons, many experienced physicians tend to prefer palladium. It has certainly been my experience in practice that many physicians who may do 10 implants per year use iodine, while many physicians who perform hundreds of implants per year, prefer palladium. That being said, many experienced physicians, including the physicians who trained me to do brachytherapy initially (Dr. Ronald Chen and Dr. Trevor Royce), use iodine and are excellent physicians with excellent outcomes as well who I would trust to do my own or a family member’s implant.
Recent Data Favoring Palladium over Iodine
As mentioned above, one recent large study showed that palladium may have better cancer control outcomes than iodine. Dr. Chad Tang and Dr. Steven Frank, the first and senior authors of the study, both from MD Anderson, retrospectively analyzed data across 8 institutions who received Pd-103 or I-125 LDR monotherapy between January 1995 and March 2017. The majority of the patients (7,504, 82%) were treated with I-125, while a minority (1,597, 18%), were treated with Pd-103. About half of the patients were treated for low risk prostate cancer and half of the patients were treated for intermediate risk prostate cancer. The median age of patients was between 64-66 years old.
Overall, the results were very good, showing the generally strong clinical results of brachytherapy monotherapy, as compared to almost any other treatment modality for prostate cancer, in general. For patients treated with I-125, biochemical failures occurred in 10.1% of patients and clinical failures occurred in 5.2% of patients. For Palladium, 3.8% of men had a biochemical failure and 3.4% had clinical failures. These differences were statistically significant and are clinically significant for men choosing between isotopes for the treatment of their prostate cancer.
Some critics of this study may argue that the differences in results may due to differences in the underlying patients rather than differences in outcomes between the isotopes. The study does not meet the gold-standard threshold of being a randomized controlled trial. However multivariable analyses adjusting for factors such as Gleason score, T category, age, PSA level, and dosimetric factors still showed that Pd-103 performed better than I-125. Another sensitivity analysis which included institutions which performed both I-125 and Pd-103 implants again showed an improvement with Pd-103. Still, as mentioned earlier, differences between physicians who choose Pd-103 vs. physicians who choose I-125, could still explain some of the differences in outcomes.
We will likely never have definitive data on the difference in outcomes between I-125 and Pd-103 implants; however, this article is about as close as we will get to a definitive answer. I have used iodine, cesium, and palladium over the course of my career, but this article has certainly solidified my choice to stick with palladium over iodine for my patients.
It is fairly clear from the data, that if given a choice, most men would pick palladium over iodine for their prostate brachytherapy isotope of choice. However, while picking the “right” isotope can be a factor in some men’s decision-making, I believe choosing a physician with experience and who you can trust is likely even more important. Picking a physician who can perform a high-quality implant is likely more important than picking someone who uses any particular isotope.
About the Author
Dr. Ankit Agarwal is a radiation oncologist/brachytherapist who specializes in the treatment of prostate cancer. Dr. Agarwal has published extensively on the treatment of prostate cancer and has treated with patients with prostate brachytherapy in North Carolina, California, and Arizona. If you are in California or Arizona, and would like to consult with one of Western Radiation Oncology’s physicians, please contact us here. Details on our Southern California clinic can be found here and details on our Arizona clinic location be found here.