Therefore, in clinical decision-making, physicians aim to identify the best treatment option concerning the timing of metastatic disease (De Novo vs. metachronous mHSPC) or tumor volume (low vs. high volume according to CHAARTED criteria). In consequence, four different types of mHSPC patients could be possibly distinguished: De Novo Low Volume (DNLV), De Novo High Volume (DNHV), Metachronous Low Volume (SecLV), and Metachronous High Volume (SecHV) mHSPC.
When this stratification is applied, manuscripts, lectures, and presentations mostly refer to a publication from Francini et al. in 2018, in which all mHSPC patients received ADT monotherapy.4 Here, all four types of mHSPC could be distinguished according to cancer-control outcomes. In consequence, little if any is known about the effect of the four mHSPC subtypes and their overall survival (OS) differences in times of intensified combination therapy for mHSPC.
We addressed this void and relied on the FRAMCAP (Frankfurt Metastatic Cancer database of the Prostate) database and identified 504 mHSPC patients for analyses. Of those, 371 (73.6%) were De Novo mHSPC vs. 133 (26.4%) metachronous mHSPC patients. Of all 504 patients, 71% vs. 11% vs. 19% received two, three, or ≥four therapy lines for metastatic prostate cancer. The majority of patients received ARSI combination therapies (58%) in mHSPC setting, followed by docetaxel combination chemotherapy (21%).
Of 504 mHSPC patients, 371 (74%) were De Novo vs. 133 (26%) secondary mHSPC.
After stratification regarding disease volume, median time to mCRPC differed significantly between DNHV vs. DNLV vs. SecHV vs. SecLV mSHPC patients, with a median time of 15 vs. 25 vs. 28 vs. 33 months for DNHV vs. DNLV vs. SecHV vs. SecLV mHSPC (p<0.001). In Cox regression models, DNHV mHSPC predicted a significantly shorter time to castration resistance (HR: 3.14, p<0.001), relative to SecLV mHSPC.
In OS analyses, all four groups also significantly differed. More specifically, median OS was 44 vs. 53 vs. 88 vs. 120 months for respectively DNHV vs. SecHV vs. SecLV vs. DNLV mHSPC. In Cox regression models, DVHV mHSPC predicted significantly shorter OS (HR: 2.80, p<0.01), relative to SecLV mHSPC.
After progression to mCRPC, all analyses were repeated. In subgroup analyses after stratification regarding metastatic volume, median OS rates were 28 vs. 32 vs. 41 vs. 42 months for respectively DNHV vs. SecHV vs. SecLV vs. DNLV mHSPC (p<0.01). In Cox regression models, DNHV mHSPC predicted significantly shorter OS, relative to SecLV mHSPC (HR: 2.12, p<0.01).
Taken together, the current study demonstrated differences in time to mCRPC and OS after the further distinction of mHSPC patients according to disease volume and the onset of metastatic disease. We could demonstrate that patients with DNHV mHSPC harbored the worst outcomes, while patients with SecLV mHSPC harbored the best prognosis. Finally, we demonstrated that these effects can also be observed after progression to mCRPC.
Written by: Mike Wenzel,1 Benedikt Hoeh,1 Philipp Kopf,1 Carolin Siech,1 Clara Humke,1 Christoph Würnschimmel,2 Thomas Steuber,3 Markus Graefen,3 Felix Preisser,3 Miriam Traumann,1 Séverine Banek,1 Luis A. Kluth,1 Felix K. H. Chun,1 Philipp Mandel1
- Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany
- Department of Urology, Kantonsspital Luzern, Lucerne, Switzerland
- Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
- Mandel P, Hoeh B, Wenzel M, et al. Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients: A Systematic Review and Network Meta-analysis. Eur Urol Focus. Published online September 1, 2022:S2405-4569(22)00176-6.
- Wenzel M, Würnschimmel C, Nocera L, et al. Overall Survival After Systemic Treatment in High-volume Versus Low-volume Metastatic Hormone-sensitive Prostate Cancer: Systematic Review and Network Meta-analysis. Eur Urol Focus. Published online April 11, 2021:S2405-4569(21)00109-7.
- Preisser F, Chun FelixK. H, Banek S, et al. Management and treatment options for patients with de novo and recurrent hormone-sensitive oligometastatic prostate cancer. Prostate Int. Published online January 18, 2021.
- Francini E, Gray KP, Xie W, et al. Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone-sensitive prostate cancer (mHSPC). The Prostate. 2018;78(12):889-895.