Proton therapy at University of Florida Jacksonville – 5-year outcomes

We have previously reported on the very good, albeit unremarkable, outcomes of proton therapy as administered at the University of Florida Jacksonville. We now have their 5-year analysis on a much larger dataset, the largest so far in the modern era.

Bryant et al. report on their retrospective analysis of the records of 1,327 men consecutively treated between 2006 and 2010. Almost all of them (98%) were treated with at least 78 GyE and those treated with hypofractionated doses were excluded.  To ensure comparable data, 113 patients were excluded for lack of adequate follow-up and use of adjuvant chemo. Other key patient characteristics included:

• ·      Low Risk: 42%
• ·      Intermediate Risk: 44%
• ·      High Risk: 14%
• ·      15% had concurrent ADT, mostly among high-risk patients
• ·      55% had radiation to seminal vesicles
• ·      3% had IMRT radiation to pelvic lymph nodes (all patients were node negative). These were excluded from the toxicity analysis.

Cancer Control

After median follow-up of 5.3 years, the 5-yr freedom from biochemical failure by risk group was:

• ·      Low Risk: 99%
• ·      Intermediate Risk: 96%

o   95% if there was only one intermediate risk factor

o   90% if there were two or more intermediate risk factors

• ·      High Risk: 74%

o   80% if there was only one high risk factor

o   32% if there were two or more high risk factors

o   87.5% who were high risk only based on Gleason 8

• ·      Among those who did not receive adjuvant ADT, the median nadir and time to nadir were:

o   Low Risk: 0.3 ng/ml and 4.2 years

o   Intermediate Risk: 0.2 ng/ml and 3.6 years

o   High Risk: 0.3 ng/ml and 2.2 years

• ·      Of the 94 patients who had biochemical failure:

o   42 had biochemical failure only

o   6 had local (biopsy-proven) failure only

o   10 had pelvic lymph node failure only

o   24 had distant metastases only

o   12 had failure in a combination of sites

• ·      Survival and freedom from metastases were 95+percent in all risk groups.

Toxicity

• ·      Acute genitourinary (GU) toxicity≥ grade 3: 1% (12 patients)
• ·      Late genitourinary (GU) toxicity≥ grade 3: 5% (61 patients)
• ·      Interventions for Grade 3 GU toxicity included catheterization, hyperbaric oxygen therapy, blood transfusion, TURP, and cauterization for symptoms including urinary obstruction, bladder irritation, hematuria, irritative symptoms, incontinence, and pain.
• ·      Larger prostates, ADT use, pre-treatment urinary therapy, diabetes, and higher doses to the bladder were associated with greater urinary toxicity.
• ·      Late gastrointestinal (GI) toxicity≥ grade 3: 1% (9 patients)
• ·      Interventions for Grade 3 GI toxicity included transfusion and colostomy for diarrhea, rectal bleeding, and ulceration.
• ·      Long-term patient-reported urinary and bowel status were unchanged from baseline.
• ·      Sexual quality of life scores declined by 22 points (29%) by 4 years post treatment (excluding those who used ADT).

Comparison to other radiation therapies

The following table shows some oncological and toxicity outcomes at 5 years for various radiation therapies as practiced at single institutions in the last several years. While differences in patient selection confound our ability to rigorously compare the therapies, they do show a general range of best-expected outcomes. Until we see the results of large-scale prospective randomized comparative trials, this is about as good as we can do in comparing them.

	Proton	IMRT	SBRT	LDR-BT	HDR-BT
5-yr bRFS
Low risk	99%	97%	97%	95%	99%
Intermediate risk	94%	94%	91%	89%	95%
High Risk	74%	87%	74%	68%	77-93%*
Late toxicity
GI grade≥3	0.6%	2%	0%	0.8%	0%
GU grade≥3	2.9%	2%	1.6%	7.6%	4.9%

bRFS= biochemical recurrence-free survival

References:

Proton: Bryant et al. http://www.redjournal.org/article/S0360-3016(16)00158-9/pdf: 78 GyE median dose, 15% received ADT

IMRT: Liauw et al. http://tct.sagepub.com/content/8/3/201 :76 Gy median dose, 50% received ADT, 4-year data

SBRT: Katz et al. http://ro-journal.biomedcentral.com/articles/10.1186/1748-717X-8-118: 35 Gy/5fx, 18% received ADT

LDR-BT (low dose rate brachytherapy – monotherapy): Kittel et al. http://www.redjournal.org/article/S0360-3016%2815%2900253-9/abstract: 18% received ADT

HDR-BT (high dose rate brachytherapy – monotherapy): Hauswald et al. http://www.redjournal.org/article/S0360-3016(15)03101-6/abstract: 43.5 Gy /6fx, 9% received ADT, 10-year data.

*For high-risk HDR-BT patients, see: HDR Brachy Boost and Monotherapy for High-Risk Prostate Cancer

Proton therapy afforded rates of cancer control comparable to the other monotherapies. Urinary and rectal toxicity were similar as well. Sexual quality of life deterioration was also similar to what we have seen for IMRT and LDR-BT (see this link). HDR-BT and SBRT seem to be superior in preserving erectile function.

If they can bring down the cost of proton therapy, it can be competitive with IMRT. As with IMRT, hypofractionation (fewer treatments) of proton therapy may deliver equivalent results at lower cost. Pencil-beam proton therapy may be able to improve toxicity still further.