3D spatial data has been generated at an extreme scale from many emerging applications, such as high definition maps for autonomous driving and 3D Human BioMolecular Atlas. In particular, 3D digital pathology provides a revolutionary approach to map human tissues in 3D, which is highly promising for advancing computer-aided diagnosis and understanding diseases through spatial queries and analysis. However, the exponential increase of data at 3D leads to significant I/O, communication, and computational challenges for 3D spatial queries. The complex structures of 3D objects such as bifurcated vessels make it difficult to effectively support 3D spatial queries with traditional methods. In this article, we present our work on building an efficient and scalable spatial query system, iSPEED, for large-scale 3D data with complex structures. iSPEED adopts effective progressive compression for each 3D object with successive levels of detail. Further, iSPEED exploits structural indexing for complex structured objects in distance-based queries. By querying with data represented in successive levels of details and structural indexes, iSPEED provides an option for users to balance between query efficiency and query accuracy. iSPEED builds in-memory indexes and decompresses data on-demand, which has a minimal memory footprint. iSPEED provides a 3D spatial query engine that can be invoked on-demand to run many instances in parallel implemented with, but not limited to, MapReduce. We evaluate iSPEED with three representative queries: 3D spatial joins, 3D nearest neighbor query, and 3D spatial proximity estimation. The extensive experiments demonstrate that iSPEED significantly improves the performance of existing spatial query systems.