A quantitative assessment of the consequences of allowing dose heterogeneity in prostate radiation therapy planning

Target dose uniformity has been historically an aim of volumetric modulated arc therapy (VMAT) planning. However, for some sites, this may not be strictly necessary and removing this constraint could theoretically improve organ-at-risk (OAR) sparing and tumor control probability (TCP). This study systematically investigates the consequences of PTV dose uniformity that results from the application or removal of an upper dose constraint (UDC) in the inverse planning process for prostate VMAT treatments. OAR sparing, target coverage, hotspots, and plan complexity were compared between prostate VMAT plans with and without the PTV UDC optimized using the progressive resolution optimizer (PRO, Varian Medical Systems, Palo Alto, CA). Removing the PTV UDC, the median D1cc reached 144.6% for the CTV and the PTV, and an average increase of 3.2% TCP was demonstrated, while CTV and PTV coverage evaluated by D99% was decreased by less than 0.6% with statistical significance. Moreover, systematic improvement in the rectum dose volume histograms was shown (a 5-10% decrease in the volume receiving 50% to 75% prescribed dose), resulting in an average decrease of 1.3% (P < 0.01) in the rectum normal tissue complication probability. Additional consequences included potentially increased dose to the urethra as evaluated by PTV D0.035cc (median: 153.4%), delivering 283 extra monitor units (MUs), and slightly higher degrees of modulation. In general, the results were consistent when a different optimizer (Photon Optimizer, Varian Medical Systems) was used. In conclusion, removing the PTV UDC is acceptable for localized prostate cases given the systematic improvement of rectal dose and TCP. It can be particularly useful for cases that do not meet the rectum dose constraints with the PTV UDC on. This comes with the foreseeable consequences of increased dose heterogeneity in the PTV and an increase in MUs and plan complexity. It also has a higher requirement for reproducing the position and size of the target and OARs during treatment. Finally, with the PTV UDC completely removed, in some cases the maximum doses within the PTV did approach levels that may be of concern for urethral toxicity and therefore in clinical implementation it may still be necessary to include a PTV UDC, but one based on limiting toxicity rather than enforcing dose homogeneity.