Treatment Comparison Chart

Description:

Radical Prostatectomy involves the surgical removal of the bulk of the gland by incisions either retropubic or perineal.

Pros:

Via incisions either through the lower abdomen or perineum, surgery accomplishes the physical removal of the tumor and gland from the body, which for some men might be a psychological benefit.

Cons:

This is the most aggressive, invasive surgery performed on the patient’s body but is the least aggressive treatment of the cancer, commonly leaving behind microscopic tumor cells. This is caused by the location of the prostate, which is surrounded by so many critical structures. Surgery cannot remove any microscopic extraprostatic extension of disease outside the prostate, which is commonly identified postoperatively. There is also a significant risk of complications (incontinence and erectile dysfunction), as well as the potential for significant blood loss and dissemination of cancer throughout the body (bones, lymph nodes, etc.).

Published Research:

Results have been reported for many years, as this was the only treatment for decades. Recent studies show a great likelihood of residual cancer after surgery, requiring additional treatment, typically radiation, which can compound surgical side effects.

References:

➢ Johns Hopkins researchers reported 80% surgical failure rate with high-risk patients (Gleason 9-10) at 15 years follow- up (Pierorazio PM, et al “Long-term Survival after Radical Prostatectomy,” Urology, 2010 Sep; 76(3) 715-721).

➢A more recent multicenter study citing research by Memorial Sloan- Kettering Cancer Center estimates that 25,000 patients annually experience treatment failure (biochemical recurrence) after radical surgery, with 50% to 95% of high-risk patients (Gleason 7-10) developing recurrence after radical surgery (Spratt DE, et al, Am Soc Clin Oncol Educ Book, 2018 May.

Description:

The Da Vinci® Surgical System and similar laparoscopic techniques use sophisticated robotic equipment to remove prostate gland tissue through a number of small incisions in the abdomen.

Pros:

Robotic surgery may be easier for patients to tolerate than major open surgery (by hand). There is less blood spillage and shorter hospital stays.

Cons:

The robotic approach is still radical surgery with similar outcomes and side effects as the open surgical approach. Success is very dependent on the operator’s level of experience. Regardless of the surgeon, more tissue is left behind with robotic surgery, which frequently contains undetected cancer cells. Extreme care must be used not to “nick” nerves, vessels or the periphery of the gland during the robotic procedure. Even in the best of hands, there will be excessive blood loss, which raises concerns of spreading cancer cells throughout the body.

Published Research:

The robotic approach is still a form of radical surgery with similar outcomes and side effects as the open surgical approach. Success is very dependent on the operator’s level of experience. Regardless of the surgeon, more tissue is left behind with robotic surgery, which frequently contains undetected cancer cells. Extreme care must be used not to “nick” nerves, vessels or the periphery of the gland during the robotic procedure. Even in the best of hands, blood loss will be 100-300 cc, which is unheard of in cancer surgery and raises concerns of spreading cancer cells throughout the body.

References:

➢ A 2016 study by the Mayo Clinic compared open, laparoscopic and robot-assisted radical prostatectomy with a 10-year follow-up. This study reported that regardless of which surgical technique was utilized, serious urinary side effects and erectile dysfunction affected about 6.4% and 37.3% of patients respectively (Jackson MA, et al, Urology, May 2016, Volume 91).

➢ A French study with 10-year follow-up of 1313 patients demonstrated no statistical difference in biochemical disease-free survival between robotic, laparoscopic and open surgery. At ten years, biochemical recurrence free survival was 53.5% high-risk patients. (Rizk J, et al, Long term biochemical recurrence free survival after radical prostatectomy for cancer: comparative analysis according to surgical approach,” Prog Urol. 2015 Mar; 25 (3):157-68).

Description:

There are many types of radiation and a number of radiation delivery systems used to target and kill cancer cells. In addition to photon external radiation, there is also proton and neutron external radiation (both are part of particle radiation—without mass). Internal radiation (Brachytherapy) can utilize several different isotopes, such as Cesium-131, Iodine-125, Iridium-192, Palladium-103 and others which may be placed permanently or temporarily.

Pros:

The advantages of radiation therapy include no cutting, no blood loss, and much lower risk of infection than surgery. The most advanced forms of radiotherapy may offer superior cancer control and far fewer complications than reported with surgery (either traditional open or robotic methods).

Cons:

In inexperienced hands and/or without the benefit of the most advanced planning and delivery technologies, there is a potential of over-irradiation, under-irradiation, unwanted outcomes, and side effects.

Published Research:

Perhaps most published of all treatment options, along with surgery.

References:

More than a century ago Benjamin Barringer, M.D., Chief Urologist at the Memorial Sloan Kettering Cancer Center commented, “Because of initial success of radium, no patient with prostate cancer should be operated on” (JAMA 1917, cited by Edward C. Halperin, et al, Principles and Practice of Radiation, 6th Edition, 2013).

Description:

Also called “seed implantation,” brachytherapy involves implanting radioactive sources (isotopes in the form of seeds or pellets) directly into the prostate gland and tumors, either permanently or temporarily.

Pros:

Brachytherapy offers the ability to place radiation sources exactly into the tumor site and to combine seeds with external radiation to optimize outcomes and minimize side effects. The procedure is minimally invasive and performed in an outpatient setting. No form of radiation is more precise. Most patients can resume normal activities without a Foley catheter the very next day after undergoing the procedure.

Cons:

Results are dependent on the skill of the brachytherapist to place the seeds appropriately. The likelihood of temporary urinary side effects is managed with medications and diet. Brachytherapy is appropriate as a single primary therapy (monotherapy) only for low-risk patients, as there is risk of late failure in intermediate and high-risk disease as a result of extraprostatic extension (ePe).

Published Research:

There have been many studies reporting long-term results (Dattoli, Blasko, Merrick, Wallner and others). Some of these studies report on combining brachytherapy with External Beam Radiation Therapy (EBRT).

References:

➢ Dicker AP, Dattoli MJ, et al, Basic and Advanced Techniques in Prostate Brachytherapy, CRC Press, first edition 2005.

➢ Dattoli MJ, Wallner KE, Merrick GS, Brachytherapy Made Complicated, Smart Medicine Press, third edition 2008.

Description:

Palladium-103 (PD-103) is an isotope of popular choice for permanent seed implant because of its qualities of short half-life and steep radial dose fall-off to surrounding anatomy, meaning the radiation is short lived and surrounding areas are spared.

Pros:

The radiation effects of PD-103 diminish by 50% every 17 days, meaning the seeds become essentially inert within 3 months, and by the unique concave design of the seed they are very stable within the gland tissue, seeds rarely migrating outside the desired placement. They needn’t be removed as they are made from tissue compatible materials that are accepted and become part of the body. Following their placement, there is no interference with MRI’s or pacemakers.

Cons:

If not performed by highly experienced physician there are fewer successful outcomes and an increase in side effects.

Published Research:

Multiple studies including many by Dattoli MJ, et al (in clinical use since 1987) who is responsible for defining clinical characteristics of PD-103, while physicist Lowell Anderson, PhD defined physical characteristics.

References:

➢ Dattoli MJ, et al, “Long-term prostate cancer control using Palladium-103 brachytherapy and external beam radiation in patients with high likelihood of extracapsular extension,” Urology. 2007 Feb; 69 (2): 334-7.

➢ Blasko JC, et al, “Palladium-103 brachytherapy for prostate carcinoma,” Int J Radiat Oncol Biol Phys. 2000 Mar 1;46 (4): 839-50.

Description:

I-125 has a longer half-life and wider dose fall-off than PD-103, meaning it takes longer for the radiation to dissipate with I-125 and there is more exposure to the surrounding tissues. They are used for permanent implantation and are both more highly penetrating than Pd-103 and more forgiving if seeds are misplaced.

Pros:

Iodine-125 is a less penetrating isotope than either Iridium-192 or Cesium-131 isotope.

Cons:

The convex (football) shape of Iodine seeds can cause them to migrate from the target. It is much more penetrating radiation than Pd-103, potentially adversely affecting bladder, urethra, rectum and sexual function.

Published Research:

There have been a number of studies comparing Iodine-125 and Palladium-103 in terms of clinical outcomes and complications.

References:

➢ Wallner K, et al, “I-125 versus Pd-103 for low-risk prostate cancer morbidity outcomes from a prospective randomized multicenter trial,” Cancer J. 2002 Jan-Feb;8(1):67-73).

➢ Herstein A, et al, “I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial,” Cancer J. 2005 Sep-Oct; 11(5): 385-9.

Description:

Iridium-192 is occasionally used for temporary brachytherapy implants often combined with external radiation. HDR is hypofractionated radiation, with limited very high dose rate treatment sessions (fractions).

Pros:

The use of new microprocessors and imaging techniques improves accuracy.

Cons:

This form of brachytherapy delivers the highest dose of radiation to the entire body (based on penetrating nature of Ir-192). When used, patients should ideally wear lead shielding goggles to avoid development of cataracts! The best case protocol utilizes 5-6 fractions (treatment sessions over time) but most patients can only tolerate 2 (and so there are rarely more than 2 sessions).

Published Research:

There are many published studies, but no long-term data supporting HDR as sole therapy, compared to permanent implants and/or combination therapy (permanent implants or HDR combined with external beam radiation).

References:

➢ An Australian study of HDR monotherapy with 10-year follow-up reported that for intermediate and high-risk patients, the biochemical disease free survival rates were 86.9% and 56.1%, respectively. Patients with 3 high-risk factors had a biochemical survival rate of only 39.5%, and that figure was inflated because these researchers did not employ a sufficiently stringent PSA nadir value to measure success. The study also reported that serious urethral strictures affected 13.6% of patients (Yaxley JW, et al, BJU Int, 2016 Sep 15).

➢ A more recent UCLA study of intermediate-risk patients with 6 treatment fractions and a follow-up of 8 years reported 90% biochemical disease-free survival, but long-term genitourinary morbidity was more than 36.3% (Patel S, et al, “High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer,” Brachytherapy, 2017 Mar-Apr; 16(2):299-305).

Description:

External Beam Radiation Therapy (EBRT) typically refers to an early version of external beam radiotherapy, but can also refer to all forms of external beam radiation (older and newer) using fractionated photon doses administered in sessions over time.

Pros:

EBRT is a nonsurgical, non-invasive treatment modality.

Cons:

Outdated EBRT technology has been shown to have many documented side effects (erectile dysfunction, proctitis and incontinence).

Published Research:

Many studies historically, which are now outdated.

References:

➢ Zelefsky MJ et al “High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.” J Urol, 2001 Sep; 166(3):876-81.

➢ Leibel SA, “Technological advances in external-beam radiation therapy for the treatment of localized prostate cancer,” Semin Oncol, 2003 Oct;30 (5):596-615.

Description:

Using photon micro-beams, Intensity Modulated Radiation Therapy (IMRT) is an advance over earlier forms of EBRT including 3D Conformal Radiation Therapy.

Pros:

IMRT is a more controlled, accurate and effective version of EBRT and 3D Conformal Radiation Therapy. It is non-invasive with fewer side effects than earlier external radiation options.

Cons:

Early generations of IMRT were rapidly improved upon and are now already considered “old” technology.

Published Research:

A number of outdated studies of IMRT nonetheless support the results achieved with recent innovations including RapidArc®, Tomotherapy (see below), True Beam technology, etc.

References:

➢ Zelefsky MJ, “Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer,” Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):125-9.

➢ Spratt DE et al, “Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer, Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):686-92.

Description:

4D-IG IMRT represents the latest generation of IMRT, with the most exquisite control of treatment micro-beams. When combining multiple 4D technologies (at least 5) an individual level of precision is realized and has been called Dynamic Adaptive Radiotherapy (DART).

Pros:

This most advanced radiation treatment protocol utilizes an ensemble of technologies to focus, aim and deliver a microbeam of photon radiation to a target the size of a voxel (a dot, or cubic mm – mm3), accurately every time. Included in the suite are strict immobilization techniques using Vac-Lock assistance, motion sensing tracking cameras, “exact couch” and “exact arm” positioning, electronic online portal imaging “portal vision” and portal dosimetry, electronic on-board portal imaging, 4th generation cone beam tomography, real-time 4D soft tissue and bone to bone matching capability, 2nd generation respiratory gating tracking, along with VisionRT and AlignRT surface guidance.

Cons:

This highly advanced technology is not yet widely available. It is costly to maintain numerous 4D technologies as a result of 6-figure service contracts and minimal reimbursement.

Published Research:

Few long-term results, but this advanced technology is based on a successful history of radiation therapy technologies.

References:

➢ Zelefsky, MJ, “Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer, Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):125-9.

Description:

This treatment protocol involves using two or more types of radiation, sometimes with hormonal therapy, to defeat cancer.

Pros:

Cancers of all sites have proven to respond best to multiple modalities; (i.e. EBRT with brachytherapy). Most patients experience only temporary and manageable side effects.

Cons:

Success with Combination Radiotherapy is dependent on expertise of practitioner and staff, and requires sophisticated, expensive equipment for integrated treatment planning.

Published Research:

In 2009 and 2010, the Dattoli team reported the most successful long-term cure rate at 16 years combining EBRT with PD-103 brachytherapy for intermediate and high-risk prostate cancer. Results were supported by a recent multicenter, metaanalysis study showing combined EBRT and brachytherapy superior to surgery and EBRT alone.

References:

➢ Dattoli MJ, et al, “Long-term outcomes for patients with prostate cancer having intermediate and high-risk disease, treated with combination external beam irradiation and brachytherapy” Journal of Oncology, July 2010.

➢ Kishan AU, “Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer,” JAMA, 2018 Mar 6;319(9):896-905.

Grimm P, et al, “Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group,” BJU Int, 2012 Feb;109 Suppl 1:22-9.

Description:

DART, developed at the Dattoli Cancer Center & Brachytherapy Research Institute, is made possible only by the use of multiple 4-D imaging and delivery technologies that account for motion of the prostate, prostatic tumors and critical structures during treatment for “interfractional” and especially “intrafractional” real time adjustments and optimization.

Pros:

DART is the only form of radiation that can fully adapt during treatment to motion of the prostate and other organs, as well as sub-select tumors and lymph nodes, using real time control and extreme precision allowing the highest accurate dose to the target while avoiding healthy tissues.

Cons:

Most of the 4-D technologies are expensive without appropriate reimbursement, making this method fiscally out of reach for most providers. True DART in its most advanced incarnation is currently available only at the Dattoli Cancer Center.

Published Research:

Published research is evolutionary – in process, since 2008 (yet already “time-tested” since this is a dramatic improvement upon previous successful radiation delivery and imaging technologies).

References:

➢ Cash J, Dattoli MJ, et al, “Combined Modality Treatment for Prostate Cancer with Dynamic Adaptive Radiation Therapy,” 2009, Radiology Nursing, Vol 28 # 3; 87-95.

➢ Dynamic Adaptive Radiotherapy (DART™), Targeting Moving Tumors, Varian Medical Systems Initiative, American Society for Therapeutic Radiology and Oncology (ASTRO) conference, Denver, Colorado, October 2005. The following year, Dr. James Cox of the M. D. Anderson Cancer Center, in an article entitled “Radiation oncology of the future ,” wrote that, “Dynamic adaptive radiation therapy implies the possibility of frequent repetitions of imaging and treatment planning.” Dr. Cox showcased DART with a presentation at the ASCO conference in Boston, Massachusetts.

Description:

Conventional IMRT is fractionated, typically given to the patient in small daily doses (fractions), usually five days a week over 8 to 10 weeks. Delivering small, incremental doses over time decreases the chance of damaging healthy tissue. With moderately hypofractionated IMRT, larger doses are administered over a much shorter period of time, often 4 to 6 weeks. With extreme, ultra-hypofractionated radiotherapy, the dose is even higher and the duration of treatment is even shorter (5-6 fractions or fewer).

Pros:

Convenience. Hypofractionated IMRT shortens the course of treatments (fewer fractions).

Cons:

The majority of studies suggest that acute and late side effects are higher with hypofractionated IMRT than with conventional IMRT. Acute toxicity results in long-term injury to surrounding, healthy tissues (i.e. rectum, bladder, urethra, neurovascular bundles and other critical neighboring structures).

Published Research:

There are few long-term published results; mostly low and intermediate risk patients with only 5 years of follow-up.

References:

➢ The published guidelines of the American Society of Clinical Oncology (ASCO) recommend that physicians should counsel patients about the limited follow-up beyond five years for most studies evaluating hypofractionation and the increased risk of acute and late toxicity with Moderately Hypofractionated IMRT compared to Conventional IMRT. The guidelines suggest Ultra-Hypofractionated Radiotherapy should be limited to clinical trials due to the risk of late toxicity (Morgan SC, Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline, Pract Radiat Oncol, 2018 Nov–Dec;8(6):354-360).

Description:

PBT uses protons to kill cancer cells. Unlike photons, protons are subatomic particles, which have been proven to kill cancer cells.

Pros:

Treatment with protons is non-invasive; the proton beam is excellent for treating tiny tumors of the eyes or brain or small pediatric tumors.

Cons:

Proton Beam Therapy is expensive; many insurers are no longer paying for PBT since there is no demonstrable advantage over other forms of radiation (including 3D Conformal Radiation of 25 years ago). The physical and dosimetric advantages of protons when treating tiny tumors (≤8mm) become disadvantages when treating larger areas (i.e. prostate gland plus margins and lymph nodes). Protons are often combined with photons to address periprostatic tissues and lymph nodes, while boosting dose to the gland proper with protons. There is documented risk of neutron scatter and secondary malignancies. PBT is unable to adjust targeting for real time motion. The purported advantage of Intensity Modulated Proton Beam Therapy (IMPBT) is not the same as that achieved by inverse modulation with IMRT, because IMPBT is only adding more beams (3 or 4 beams instead of 2 beams).

Published Research:

There are no clinical studies longer than 10 years and most are devoted to protons combined with photons rather than protons alone. While there are no randomized studies comparing protons vs. photons, a number of recent studies demonstrate no advantage of PBT over IMRT, while there is increased risk of rectal toxicity and erectile dysfunction with protons.

References:

➢ Sheets NC, et al, Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control, JAMA, 2012 Apr 18;307 (15):1611-20).

➢ Gray PL et al, “Patient-reported outcomes after 3-dimensional conformal, intensity-modulated, or proton beam radiotherapy for localized prostate cancer, Cancer, 2013 May 1;119(9):1729-35.

➢ A study by the University of Florida Proton Therapy Institute reported that as many as 32.3% of patients experienced rectal toxicity (Grades 1-3) after PBT (Colaco RJ et al, Int J Rad Onco Biol Phys, 2015 Jan 1;91(1):172-81).

➢ Kamran SC, et al, Proton versus photon-based radiation therapy for prostate cancer: emerging evidence and considerations in the era of value-based cancer care, Prostate Cancer Prostatic Dis. 2019 Dec;22(4):509-521.

Description:

Neutron Therapy uses Neutrons to kill cancer cells.

Pros:

Theoretically, neutron radiation therapy might be effective for treating cancers that are resistant to photon or proton radiation such as unresectable sarcomas.

Cons:

Any contact with healthy tissue can cause severe damage along with a high incidence of serious side effects. Neutrons have an unfavorable “therapeutic ratio,” meaning neutrons damage both healthy cells and cancer cells. Neutron Therapy is not widely available.

Published Research:

Neutron therapy is still experimental, and published studies do not show neutrons to be as safe or as effective as photon radiation. With the ability of photons to reach higher doses than ever before as a result of technological advances such as IMRT and brachytherapy, the concept of tumors being resistant to photons has taken on less importance in recent years.

References:

➢ Santanam L, “Intensity modulated neutron radiotherapy for treatment of adenocarcinoma of the prostate.” Int J Rad Onc Biol Phys, 2007 Aug.

➢ Snyder M, et al, “Dose escalation in prostate cancer using intensity modulated neutron radiotherapy,” Radiother Oncol, 2011 May;99(2):201-6.

Description:

Cyberknife® is a form of Stereotactic Body Radiotherapy (SBRT). This type of external radiation therapy utilizes a hypofractionated treatment regime with fewer sessions (often 5 or fewer), and very high dose rate per session. Other brands of SBRT include Novalis Tx™, GammaKnife™, and Axesse™.

Pros:

All forms of Stereotactic Body Radiotherapy offer the advantage of convenience because they shorten the course of radiation treatments from 8-10 weeks to 5 or fewer treatment sessions (fractions).

Cons:

All extreme radiation hypofractionated studies to date reveal a high risk of significant complications including high incidence of urethral/rectal fistula, bladder damage, ulcerations, bone necrosis. Beam adjustments are very difficult during treatment. Radiation delivered even slightly off-target can cause significant damage to bladder and rectum. Cyberknife® cannot treat outside the prostate where microscopic cells often exist. Cyberknife® and other SBRT ultra-hypofractionated modalities should be reserved for non-curative cases, such as men who will not live long enough to suffer harsh complications.

Published Research:

There are no long-term results published and most studies are limited to low and intermediate risk patients.

References:

➢ A 2018 multi-institutional study reported, “To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities,” (Kothari G, et al, Stereotactic Body Radiotherapy for Primary Prostate Cancer. Technol Cancer Res Treat. 2018 Jan 1).

➢ A recent multi-center 5-year study with low and intermediate-risk patients reported “excellent biochemical control” with high dose SBRT at 5 fractions but at the expense of “increased severe late toxicity,” (Hannan R, et al, “Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial,” Eur J Cancer. 2016 May;59:142-151).

➢ A recent Memorial Sloane Kettering Cancer Center study of dose escalation with SBRT with low and intermediate-risk disease reported that with a dose of 40 Gy delivered in 5 fractions, acute grade 2 rectal toxicities and urinary toxicities affected 11.4 % and 17.1% of patients respectively. (Zelefsky MJ et al, “5-Year Outcomes of a Phase I Dose Escalation Study Using Stereotactic Body Radiosurgery for Patients with Low and Intermediate Risk Prostate Cancer,” J Rad Oncol Biol Phys, 2019 Jan 3).

Description:

Helical Tomotherapy is a form of radiotherapy that uses daily CT imaging to guide treatment based on anatomy. The ring gantry design may facilitate multiple beam delivery. The radiation dose is delivered “slice by slice.”

Pros:

Increased beam directions with Tomotherapy may enable better-optimized treatment design and can be changed daily, if necessary (“interfractional” treatment).

Cons:

Tomotherapy requires longer treatment duration. 360-degree delivery increases dose to normal tissues. There is risk of inconsistent movement of the couch leading to over/under treatment of cancer tissues. Most significant is the concern about normal tissue overexposure and risk of secondary malignancies.

Published Research:

There are no long-term results for treating prostate cancer with Helical Tomotherapy.

References:

➢ A Canadian study of quality of life (QOL) within two years after treatment with helical tomotherapy reported “bowel and sexual function were significantly affected” (Pervez N, et al, Quality-of-life outcomes in high-risk prostate cancer patients treated with helical tomotherapy in a hypofractionated radiation schedule, Curr Oncol, 2012 Jun; 19(3):e201-10.

➢ An Italian short-term study reported late genitourinary toxicity at 6.6% and gastrointestinal toxicity at 5.3% of patients (Cuccia F, Hypofractionated postoperative helical tomotherapy in prostate cancer, Cancer Manag Res. 2018 Oct 29; 10:5053-5060.

Description:

The Calypso® 4D Localization System is an attempt to address the problem of organ motion in external radiation therapy by utilizing global positioning system (GPS) technology to track motion of the patient and prostate gland during daily radiation treatment sessions.

Pros:

The Calypso system can track motion during treatment better than earlier technology.

Cons:

Although motion is tracked, the program is unable to make beam adjustments during treatment.

Published Results:

No long-term studies published.

References:

➢ Sandler, et al; Urology, Vol. 75, 5, 1004-1008, 2010.

➢ Berglund RK, et al, BJU Int, 2012 Sep;110(6):834-9.

Description:

This is a relatively new product from Varian Medical Systems that offers a complete IMRT treatment with a single rotation of the linear accelerator delivery system around the patient. The technology is known as “volumetric modulated arc therapy” or “rotational radiotherapy,” and the main advantage touted by the manufacturer is that treatment time may be 2 to 10 times faster than earlier generations of IMRT systems, including DART. The accelerated treatment time (under 3 minutes) would enable a cancer center using this technology to treat many more patients; however, it should be noted that the safety and efficacy of this approach have not been demonstrated.

Pros:

Shorter treatment time for patient; reduction of staff for centers offering this modality.

Cons:

Continuous open beam (arc) causes higher integral dose and more tissue expsoure, which is potentially harmful. Rapid treatment times (accelerated radiation) predict increased toxicity. No distinct clinical benefit for patient has been established.

Published Research and References:

None – there are no clinical toxicity studies to cite. We have significant concerns about high radiation dose rates, which have never been studied. It should be noted that Since April 2010, Varian Medical Systems has been marketing another hi-tech system known as TrueBeam™ that is being combined with RapidArc™ at some centers, or combined with the Calypso 4D® Localization Tracking System at other centers.

Description:

As a primary treatment, Cryotherapy (aka Cryosurgery and Cryoablation) uses the process of freezing and thawing to destroy cancer cells. It is also used as a salvage therapy after other primary treatments fail.

Pros:

Cryotherapy is performed without cutting and offered on outpatient basis. Recent improved methods reduce risk of rectal injury. The treatment can be repeated.

Cons:

There is a high risk of permanent erectile dysfunction (ED); some risk of incontinence, rectal fistula, and urethral sloughing following treatment. Cancers often return since the urethra must be warmed (an area where cancer cells live and spread), and prostate cancers are frequently more aggressive after recurrence. Cryotherapy is not recommended when cancer is suspected to have spread beyond the prostate gland. It is not able to treat lymph nodes.

Published Research:

There are very few long-term studies despite cryotherapy dating back to the 1980s.

References:

➢ Long, JP, et al, “Five-year retrospective, multi-institutional pooled analysis of cancer-related outcomes after cryosurgical ablation of the prostate” (Urol 57:518-523, 2001).

➢ A more recent 5-year study from Johns Hopkins School of medicine reported that low, intermediate and high-risk patients experienced biochemical disease-free survival (BDFS) rates of 90.4%, 81.1%, and 73.6%. Those results are likely inflated by a PSA nadir of 0.4 ng/ml. (Levy DA et al, J Urol, 2014 Nov; 192(5):1380-4.).

➢ A 2016 multi-institutional study led by Duke University investigated cryosurgery as a primary treatment for high-risk patients and reported 5-year biochemical progression-free survival rate was only 59.1% (Tay KJ, et al, J Endourol. 2016 Jan; 30 (1): 43-8).

Description:

HIFU uses focused sound waves from a rectal probe in order to heat the target area, to ablate cancer cells and destroy tissue. Several hour-long sessions are required.

Pros:

HIFU is non-ionizing, non-invasive (no cutting, no blood loss); treatment can be repeated. HIFU can be used as a potential salvage therapy after failed radiation.

Cons:

After HIFU treatment, cancers usually return and are often more aggressive. It is not recommended for cases where cancer is suspected to have spread beyond the prostate. HIFU can only treat the prostate proper and will therefore miss extra-prostatic extensions. Cannot treat lymph nodes. Rectal and bladder complications are irreparable.

Published Research:

Few studies and no long-term results reported.

References:

➢ A French study reported “43.7% of patients experienced biochemical recurrence in less than 5 years” (Misrai V, et al, “Oncologic control provided by HIFU therapy as single treatment,” World J Urol 2008 Oct;26(5):481-5).

➢ A Duke University study reported a high percentage of “positive post-treatment biopsies, non-uniform treatment protocols, and absence of long-term follow-up” (Schulman AA, et al, “High-intensity focused ultrasound for focal therapy: reality or pitfall?” Curr Opin Urol. 2017 Mar;27(2):138-148).

Description:

Focal Ablation therapies such as Focal Cryoablation and Focal HIFU have been investigated in recent years to treat cancer that is limited to the prostate gland or prostate bed. These therapies should only be used for salvage cases after primary treatment failure because over time prostate cancer will likely occur elsewhere in the gland after focal therapy and will require repeated treatment with a likelihood of increased complications. Cancer is a “field effect” disease (aka “field cancerization”), meaning that whatever biochemical, environmental and genetic forces were in place to cause the growth of the primary tumor are still at work after focal therapy in another part of the prostate gland.

Pros:

Ability to target and treat clearly identified areas of recurrent prostate cancer with fewer side effects than whole-gland salvage therapy.

Cons:

Patients eligible for this approach are usually limited to those having unilateral prostate cancer (tumor confined to one lobe). Only recommended for salvage cases, not as primary therapy because of the risk of morbidity and relapse, with the entire gland at risk for cancer “field effect.”

Published Research:

There are no long-term results, though there is a growing body of published studies for focal ablation utilizing a number of energy modalities, cryoablation, HIFU, laser ablation, photodynamic therapy, focal brachytherapy, and radiofrequency ablation.

References:

➢ Edison E, et al, “Focal Ablation of Early-Stage Prostate Cancer: Candidate Selection, Treatment Guidance, and Assessment of Outcome,” Urol Clin North Am, 2017 Nov; 44(4): 575-585.

➢ A University of Southern California study reported that “For carefully selected patients, Salvage Focal Cryoablation (SFC) is an option associated with lower treatment-related morbidity compared with Salvage Total Cryoablation (STC) (de Castro Abreu AL , et al, “Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapy,” BJU Int, 2013 Aug; 112(3): 298-307. A recent multi-institutional study of salvage focal HIFU for recurrence reported 7-year survival at 72% “at the expense of significant morbidity” (Crouzet S, “Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy,” BJU Int, 2017 Jun; 119(6):896-904).

➢ A recent British study reported biochemical disease free survival with focal HIFU of “100%, 61% and 32% at 3 years follow-up in the low-, intermediate- and high-risk groups pre-salvage HIFU, respectively.” (Kanthabalan A, et al, “Focal salvage high-intensity focused ultrasound in radio-recurrent prostate cancer,” BJU Int, 2017 Aug; 120(2):246-256.

Description:

Hormonal Therapy, also known as Androgen Deprivation Therapy (ADT) utilizes various hormonal agents to decrease production of testosterone and inhibit the growth and progress of cancer. Hormones are used as palliative therapy for patients with advanced disease; and also used with primary treatments like radiation for localized prostate cancer to enhance effectiveness and to shrink gland size.

Pros:

Hormonal therapy is given as easy oral and/or injection treatment. It offers survival advantages to patients with advanced disease and patients with localized disease undergoing primary treatments, such as radiation therapy. Hormones have a synergistic effect when used with radiation, improving results. This synergistic effect has not been documented with radical surgery.

Cons:

Hormone therapy can be expensive with potential side effects depending on the agent or combination of agents. Hormones often bring with them a high risk of erectile dysfunction and menopause-like symptoms (hot flashes, loss of libido, fragile bones, enlarged painful breasts). With long-term use (one year or more), ADT may cause increased risk of osteoporosis, cardiovascular disease, strokes, diabetes and cognitive dysfunction. Cancers eventually become resistant to hormonal therapy.

Published Research:

Many studies indicate that hormones are appropriate for late stage patients only when all other options have been expended, since hormonal therapy is non-curative in intent. There are also studies supporting the use of hormones to reduce the size of the prostate with early stage patients undergoing primary therapy and to synergize the effects of radiation in intermediate to high-risk disease.

References:

Multiple long-term follow-up studies show the benefit of ADT in conjunction with curative radiation and following radical surgery, including the following:

➢ European Organization for Research and Treatment of Cancer (EORTC 22863) (Eur Urol. 1998 Dec; 35 Suppl S1:23-26.).

➢ Radiation Therapy Oncology Group (RTOG) 9202 (Hanks et al, J Clin Oncol. 2003 Nov 1;21(21):3972-8).

➢ Rusthaven CG, et al, “Improved Survival With Radiation in Addition to Androgen Deprivation Therapy,” J Clin Oncol. 2016 Aug 20;34 (24):2835-42).

➢ Shipley WJ, et al, “Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer,” N Engl J Med. 2017 Feb 2;376(5):417-428).

There are also recent studies demonstrating long-term hormonal therapy carries the risk of serious side effects that require mitigating therapies:

➢ Nguyen PL, et al, “Adverse effects of androgen deprivation therapy and strategies to mitigate them,” Eur Urol, 2015 May;67(5):825-36.

➢ Saylor PJ, et al, “Prostate cancer survivorship: prevention and treatment of the adverse effects of androgen deprivation therapy,” Gen Intern Med; 2009 Nov; 24 Suppl 2:S389-94.

➢ Keating NL, et al. “Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.” J. Clin Oncol, 2006 Sep 20; 24(27): 4448-56.

Description:

With Active Surveillance (AS) for low-risk patients, no treatment is planned but close monitoring of cancer progression with PSA testing every 3 to 6 months, along with periodic biopsies and Multiparametric MRI (mp-MRI) tests are recommended. No absolute follow-up guidance has yet been established.

Pros:

Avoids primary treatment costs and side effects (incontinence and/or erectile dysfunction); there are new molecular biomarkers and genomic tests now being used for monitoring patients.

Cons:

Only recommended for early prostate cancer that may be indolent (though a misdiagnosis can lead to an incurable scenario). Necessary periodic repeat biopsies increase risk of infection and may lead to erectile dysfunction. When treatment becomes necessary, cancer has advanced requiring more aggressive treatment with increased risk of side effects.

Published Research:

Modern Active Surveillance is evolving, so no well-established outcome data is available at this point.

References:

Dattoli MJ, “Active Surveillance: A Dark Side?” (PAACT, Cancer Communication, Winter 2014).

Description:

Following diagnosis, the patient decides to forego active treatment and may undergo periodic re-staging to assess disease progression. Watchful Waiting as the patient’s choice to postpone treatment has been superseded in recent years by Active Surveillance, which involves increased monitoring while primary treatment is postponed. Watchful Waiting is recommended only for elderly men with less than 5 years life expectancy (unless highly aggressive tumor or very high volume tumor).

Pros:

‘No treatment’ is easier to tolerate as long as cancer does not spread.

Cons:

Waiting can be psychologically difficult for patient when it becomes “Watchful Worrying.” Without treatment, prostate cancers often become more aggressive while PSAs may even diminish leading to a false sense of security.

Published Research:

There is little published data, with watchful waiting now superseded by Active Surveillance.

References:

➢ Etzioni R, et al, reported a 4-fold increase in prostate cancer mortality without treatment. (“Studies of prostate cancer mortality: caution advised,” Lancet Onc, 2008 May 9(5): 407-9).