SBRT has excellent outcomes for intermediate-risk patients


Stereotactic body radiation therapy or SBRT (sometimes referred to as SABR or SHARP or CyberKnife) has had excellent 7-year outcomes in an update of the consortium study, including data from 10 single-institution trials and two multi-institutional trials. Amar Kishan presented the results of his analysis at the ASTRO meeting on Wednesday; updates were included in a press release.

The meta-analysis covers 2,142 low- (n = 1,185) and intermediate-risk men treated with SBRT between 2003 and 2012. Intermediate-risk men were further subdivided into “favorable intermediate-risk” (n = 692) and “unfavorable intermediate-risk” (n = 265) per the NCCN definitions.

After a median follow-up of 6.9 years, the 7-year biochemical recurrence-free survival rates were:

  • Low risk: 95.5 percent
  • Favorable intermediate risk: 91.4 percent
  • Unfavorable intermediate risk: 85.1 percent

Low-risk patients and some of the favorable intermediate-risk patients would be diverted to active surveillance today. The 10-year biochemical recurrence-free survival for the intermediate-risk patients compares favorably with data for other types of treatment, as follows:

  • Surgery: favorable intermediate-risk (PSA = 6.0, T1c, GS 3 + 4, 33 percent cancerous cores): 81 percent (mean of 5- and 10-year progression-free survival) (1)
  • Surgery: unfavorable intermediate-risk (PSA = 6.0, T1c, GS 4 + 3, 67 percent cancerous cores): 53 percent (mean of 5- and 10-year progression-free survival) (1)
  • Hypofractionated IMRT (5-year): 85 percent (2)
  • Conventional IMRT (5-year): 85 percent (2)
  • Low-dose-rate brachytherapy: favorable intermediate risk (mean of 5-year and 10-year): 85 percent (3)
  • Low-dose-rate brachytherapy: unfavorable intermediate risk (5-year): 81 percent (3)
  • Brachy-boost therapy: unfavorable intermediate risk (10-year): 92 percent (4)

Note: These are not randomized comparisons, which is the only valid way of comparing with a high level of accuracy.

There were no prostate cancer-related deaths.

Acute toxicity (i.e., occurring within 3 months of treatment) was low:

  • Urinary toxicity — Grade 2: 8.8 percent; Grade 3: 0.3 percent
  • Rectal toxicity — Grade 2: 3.2 percent; Grade 3; 0.0 percent

Late-term cumulative toxicity was also low:

  • Urinary toxicity — Grade 2: 7.9 percent; Grade 3 or higher: 2.1 percent
  • Rectal toxicity — Grade 2: 3.2 percent; Grade 3 pr higher: 0.2 percent

Late-term urinary toxicity of Grade 3 or higher of 2.1 percent compares favorably to this type of toxicity associated with other radiation monotherapies reported in other studies. For example:

  • Low-dose-rate brachytherapy: 7.6 percent (5)
  • High-dose-rate brachytherapy (three fractions): 11 percent (6)
  • Hypofractionated IMRT (70 Gy/28 fractions): 3.5 percent (7)
  • Conventionally fractionated IMRT: 2.3 percent (7)
  • Brachy-boost therapy: 19 percent (8)

Late-term rectal toxiicity of Grade 3 or higher of 0.2 percent also compares favorably to this type of toxicity associated with other radiation monotherapies reported in other studies. For example:

  • Low-dose-rate brachytherapy: 0.8 percent (5)
  • High dose rate brachytherapy (three fractions): 1 percent (6)
  • Hypofractionated IMRT (70 Gy/28 fractions): 4.1 percent (7)
  • Conventionally fractionated IMRT: 2.6 percent (7)
  • Brachy-boost therapy: 9 percent (8)

This 7-year analysis on a large group of patients from multiple sites should make intermediate-risk patients comfortable in choosing SBRT, especially if they are favorable intermediate risk. For patients who are unfavorable intermediate risk, brachy-boost therapy affords incomparable oncological control, but at the risk of much higher rates of late-term urinary and rectal toxicity.

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

8 Responses

  1. In my opinion: Some facts about EBRT/SBRT, prostate radiotherapy (EBRT-external beam radiation therapy) for cancer treatment.

    New technology consists of Proton, IMRT, SBRT, IGRT, VMAT, TrueBeam, Cyberknife, etc. This newer, faster, more accurate equipment is a good selling point to patients. However, as far as reducing long-term side effects, only small gains have been made with the newer radiotherapy equipment. A patient should be extremely skeptical if exaggerated claims are made about reduced long-term side effects, especially fatigue and ED rates from newer equipment. 44% decreased orgasm intensity and multiple forms of sexual dysfunction. Patients should inquire as to the treatment plan: dose (in Greys) and fractions, margins, testicular dose, constraints and age of radiotherapy equipment to ensure excessive radiation exposure treatment is not given that can result in additional side effects. Patients should be aware that pelvic shaving, permanent tattoo markers, fiducial marker (small seeds) are sometimes placed in the prostate, MRI, CT scan, photographs, catheters and other procedures may or may not be required. Radiotherapy can also occasionally result in secondary cancers and damage to “organs at risk” (organs close to the prostate). Radiation has a high probability of sexual dysfunction and fatigue, just as high with the newer equipment. ED rates estimated at 35% to 75% or higher, 93% at 15 years.

    Prostate radiotherapy EBRT/SBRT can sometimes result in a 5% to 30% or more temporary or permanent drop in testosterone levels, excluding hormone therapy. This drop is determined by the testicular radiation dose (treatment equipment and planning). Always ask for a printout of testicle dose and constraints for prostate radiotherapy to ensure your testicles are not over-radiated, also include the CT scan exposures. With radiotherapy, robotic arm equipment and the testicles included in the treatment field can result in a major drop in testosterone. Have your testosterone levels tested before and months after EBRT prostate treatment.

    When inquiring about a SBRT 5 day (5 fraction, 35 to 36 Gy) treatment the testicular dose should be well under 1 Gy and the testicles should always be excluded from the treatment field. In the early days of Cyberknife including them was a standard occurrence.

  2. Dear JJ:

    Most of the things you are talking about are things that used to occur and should not be occurring today at the majority of reputable centers. However, I do agree with you that any wise patient should be asking all sort of questions about any form of treatment for prostate cancer (all forms of radiotherapy included). At most reputable centers the majority of things you mention would be brought up by the radiotherapy team prior to treatment. If any radiation center isn’t willingly answering questions like this, any wise patient should walk a way and go to a center that does answer the patient’s questions willingly and thoroughly.

  3. JJ:

    Side effects certainly do occur due to radiation, but they have gotten a lot better due to highly conformal radiation, intensity modulation, intrafractional tracking (with SBRT), and tighter dose constraints possible on newer LINACs. As you see in the numbers I provided above, serious late-term transient side effects are a rarity, and chronic side effects are even more rare.

    Fatigue is very low with SBRT because fatigue increases with the number of treatments. ED due to radiation is very hard to estimate because the median age at the time of radiation is about 70 in most studies — so it is unsurprising that 15 years later, an 85-year-old man has ED. When efforts are taken to separate the effects of aging, as Keyes has shown, full potency preservation at 7 years post-treatment is expected for 78% of men under 60 getting brachytherapy, but most of that loss (59%) is due to aging, not the therapy.

    The drop in testosterone levels following radiation is typically transient. It usually returns to baseline within a year (as it did for me). It does not seem to be related to testicular dose, which is minimal, and only due to scattered radiation. In this study, 75% of men receiving radiation had a decrease in testosterone, but 69% of them recovered to within 90% of baseline: advanced age, higher BMI, higher baseline testosterone level, and lower nadir level were risk factors.

  4. Huge gains in reduced side effects

    JJ: You wrote: “… However, as far as reducing long-term side effects, only small gains have been made with the newer radiotherapy equipment….”

    Sitemaster and Allen have made excellent points. I want to add just one point: to me, a 19.5 year prostate cancer survivor of a once life-threatening case who had radiation with attempt to cure in 2013, those reductions in side effects with more modern techniques, including SBRT, have been huge! Maybe the gains are small when you compare only fairly modern techniques, with IMRT and IMRT/IGRT as a baseline, but the gains look large when you compare to “traditional” or the later “3D conformal beam” radiation without much image guidance. That success in reduced side effects is even more impressive when you look at the markedly enhanced non-recurrence rates that accompany those reductions in side effects.

  5. Allen,

    After prostate cancer treatment, ED estimates are deceptive because rates are given after the use of ED drugs. Without ED drugs, ED is often much higher. Statistics for ED percentages from treatment are usually quoted after treatment with Viagra or other ED drugs, therefore most statistics are very misleading.

    A temporary or permanent drop in testosterone is mostly dependent on the testicular dose, equipment used, planning, constraints, etc. See this paper by Blacksburg et al. from 2017.

  6. Some studies report use of ED meds, some don’t. It is inconsistent, which is part of the problem. I very much agree that it should be consistently reported. But PROSTQA was consistent — the exact same questions were asked of everyone. In fact, they specifically asked if PDE-5 inhibitors were used and how effective they were (Table 6 in the Alemozaffar et al. study).

    The paper you cited does not relate testicular dose to serum testosterone. In fact, an in-depth analysis of available data showed inconsistent correlations:

    “A number of studies have attempted to estimate or measure the scatter radiation dose to the testicles in the setting of prostate RT. Oermann et al. estimated a median dose of 2.1 Gy (range, 1.1-5.8 Gy) in the setting of robotic radiosurgery SBRT. The study by King et al.19 estimated that testicular scatter doses from intensity modulated RT ranged from 0.84 Gy with PORT to 6.3 Gy in the setting of pelvic intensity modulated RT with a prostate boost. Previous studies used thermoluminescence dosimetry (TLD) measurements to estimate the testicular scatter dose to be in the range of 2 Gy, or approximately 3% of the prescribed dose to the prostate,2,4,20,21 although an earlier TLD study by Grigsby5 estimated a testicular dose of 4.5 to 6.0 Gy.”

    “Leydig cell damage may be age dependent, with older patients experiencing a greater sensitivity to low-dose radiation in the 2 Gy range. Although the aforementioned studies address the effect of low-dose radiation, or lack thereof, in older men who are treated for prostate cancer, 2 earlier studies of higher-dose testicular irradiation in younger men showed no effect on ST. The study by Rowley et al.22 involved the irradiation of the testes of 67 male prisoners with an age range of 25 to 52 years. The doses ranged from 0.08 to 6 Gy. The investigators reported that no significant effect was found on the ST levels of the irradiated patients. The study by Shapiro et al.23 followed-up 27 men who had undergone RT for soft-tissue sarcomas. They failed to show changes in the ST levels within 30 months of follow-up. The patients in that series had received a wide range of testicular doses, from 0.01 to 25 Gy.”

  7. This SBRT study, at 4 years, shows ED rates at about 50% for all patients and about double for patients taking no ED meds.

    According to another study by King et al.:

    “The testicular constraints for SBRT 5 fraction is 2 Gy. Robotic arm equipment and non-testicular avoidance (TA) beam arrangements will violate the 2 Gy constraint and lower testosterone. Shooting beams through the testicles or violating the 2 Gy constraints is unwise and will lower testosterone.”

  8. Thankfully things have improved since that 2010 study on SBRT and ED. See here for our most recent update on ED and SBRT.

    As for the second quote, also from an early study, Dr King’s recommendations on SBRT dose constraints are widely respected and have been incorporated in radiation plans for many years now. Yet testosterone still drops after radiation even when those testicular dose constraints are met. The results are inconsistent. We have to look for another cause,

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